A Study of Carboplatin Plus Etoposide With or Without Ate... | NCT02763579

NCT02763579

ID	Type	Description	Link
2015-004861-97	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Atezolizumab + Carboplatin + Etoposide	Experimental	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Drug: Carboplatin Drug: Etoposide
Placebo + Carboplatin + Etoposide	Active Comparator	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Drug: Carboplatin Drug: Etoposide Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody	Drug	Atezolizumab intravenous infusion was administered at a dose of 1200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) and maintenance phase (Cycle 5 onward).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).	Baseline until PD or death, whichever occurs first (up to approximately 23 months)
Duration of Overall Survival (OS) in the Global Population	OS is defined as the time from randomization to death from any cause.	Baseline until death from any cause (up to approximately 23 months)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population	Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

Eligibility Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Florida Cancer Specialists - Fort Myers (Broadway)		Fort Myers	Florida	33901	United States
Florida Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38280181	Derived	Bernabe R, Liu SV, Sanchez-Gastaldo A, Alonso Garcia M. Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab. Oncol Ther. 2024 Mar;12(1):175-182. doi: 10.1007/s40487-023-00257-0. Epub 2024 Jan 27.
37931445	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo + Carboplatin + Etoposide - Global	Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 6, 2019

Arm/Group Information

ID	Title	Description
BG000	Placebo + Carboplatin + Etoposide - All	All participants in the Global or China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
BG001	Atezolizumab + Carboplatin + Etoposide - All	All participants in the Global or China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0004.3± 4.2(4.2 to 4.5) OG0015.2± 4.4(4.4 to 5.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0170		Stratified Hazard Ratio	0.77			2-Sided	95	0.62	0.96					Superiority

Primary

Duration of Overall Survival (OS) in the Global Population

OS is defined as the time from randomization to death from any cause.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Median

95% Confidence Interval

Months

Baseline until death from any cause (up to approximately 23 months)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Median

95% Confidence Interval

Months

First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

PFS Rate at 6 Months and at 1 Year in Global Population

PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

6 months, 1 year

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

OS Rate at 1 Year and 2 Years in the Global Population

OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Number

Percentage of participants

1 year, 2 years

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population

TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant.

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Posted

Median

95% Confidence Interval

Month

Baseline until deterioration per symptom subscale (up to approximately 23 months)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Percentage of Participants With at Least One Adverse Event in the Global Population

The percentage of participants with at least one adverse event in the global population.

The safety population included all treated participants, defined as participants who received any amount of any component of study treatment. For the safety analyses, patrticipants who received any amount of atezolizumab were analyzed as part of the Atezo + CE arm, even if atezolizumab was given in error.

Posted

Number

Percentage of participants

Baseline until up to 90 days after end of treatment (up to approximately 49 months)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population

The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.

ADA analyses were based on ADA observations from participants who had received atezolizumab treatment and were evaluated for immunogenicity.

Posted

Number

Percentage of participants

Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)

ID	Title	Description
OG000	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Units

Secondary

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population

Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Posted

Mean

Standard Deviation

μg/mL

Post-dose Day 1 of Cycle 1 (cycle length = 21 days)

ID	Title	Description
OG000	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Units	Counts
Participants

Secondary

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population

Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Posted

Mean

Standard Deviation

μg/mL

Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)

ID	Title	Description
OG000	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Units	Counts
Participants

Secondary

Plasma Concentration of Carboplatin in the Global Population

Plasma concentration of carboplatin in the Global population.

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Posted

Mean

Standard Deviation

ng/mL

Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Secondary

Plasma Concentration of Etoposide in the Global Population

Plasma concentration of etoposide in the Global Population.

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Posted

Mean

Standard Deviation

ng/mL

Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

ID	Title	Description
OG000	Placebo + Carboplatin + Etoposide	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
OG001	Atezolizumab + Carboplatin + Etoposide	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + Carboplatin + Etoposide - Global	Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	11	196	69	196	187	196
EG001	Atezolizumab + Carboplatin + Etoposide - Global	Participants in the Global population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	5	198	81	198	191	198
EG002	Placebo + Carboplatin + Etoposide - China	Participants in the China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	1	52	14	52	52	52
EG003	Atezolizumab + Carboplatin + Etoposide - China	Participants in the China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	3	57	22	57	56	57

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0014 events3 affected198 at risk EG0021 events1 affected52 at risk EG0030 events0 affected57 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0009 events9 affected196 at risk EG0015 events5 affected198 at risk EG0022 events2 affected52 at risk EG003
Granulocytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Myelosuppression	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0008 events8 affected196 at risk EG0017 events7 affected198 at risk EG0021 events1 affected52 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events4 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events4 affected196 at risk EG0015 events5 affected198 at risk EG0022 events2 affected52 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events3 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Cardiopulmonary failure	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Palpitations	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Autoimmune thyroiditis	Endocrine disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Abdominal adhesions	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Autoimmune colitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0013 events3 affected198 at risk EG0020 events0 affected52 at risk EG003
Diverticular perforation	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Gastric ulcer perforation	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Lip oedema	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Proctitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected196 at risk EG0013 events3 affected198 at risk EG0020 events0 affected52 at risk EG003
Asthenia	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Chest discomfort	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Chest pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Death	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Fatigue	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0013 events3 affected198 at risk EG0020 events0 affected52 at risk EG003
General physical health deterioration	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Influenza like illness	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pyrexia	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0021 events1 affected52 at risk EG003
Systemic inflammatory response syndrome	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Bronchitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Cytomegalovirus infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Device related sepsis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Lung abscess	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Myelitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Neutropenic sepsis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pneumonia	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG00011 events10 affected196 at risk EG00115 events12 affected198 at risk EG0025 events4 affected52 at risk EG003
Pulmonary sepsis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pyopneumothorax	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Sepsis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Septic shock	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Radiation oesophagitis	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Blood bilirubin increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Blood creatinine increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
C-reactive protein increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Liver function test increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0022 events2 affected52 at risk EG003
Platelet count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Transaminases increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events4 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0021 events1 affected52 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Dysarthria	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Guillain-Barre syndrome	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Somnolence	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Spinal cord oedema	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Syncope	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0013 events3 affected198 at risk EG0020 events0 affected52 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Trigeminal neuralgia	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Alcohol abuse	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Depression	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Tubulointerstitial nephritis	Renal and urinary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events2 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0011 events1 affected198 at risk EG0021 events1 affected52 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0012 events2 affected198 at risk EG0021 events1 affected52 at risk EG003
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0012 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0014 events2 affected198 at risk EG0020 events0 affected52 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Peripheral artery occlusion	Vascular disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Superior vena cava syndrome	Vascular disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Venous thrombosis limb	Vascular disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG00084 events69 affected196 at risk EG001101 events86 affected198 at risk EG00250 events40 affected52 at risk EG00376 events46 affected57 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG00032 events19 affected196 at risk EG00144 events24 affected198 at risk EG00222 events14 affected52 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG000105 events66 affected196 at risk EG001122 events71 affected198 at risk EG00241 events17 affected52 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG00044 events29 affected196 at risk EG00146 events31 affected198 at risk EG00231 events16 affected52 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events1 affected196 at risk EG0012 events2 affected198 at risk EG0024 events4 affected52 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events5 affected196 at risk EG00111 events11 affected198 at risk EG0020 events0 affected52 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG00120 events20 affected198 at risk EG0022 events2 affected52 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0015 events5 affected198 at risk EG0021 events1 affected52 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG00011 events11 affected196 at risk EG00110 events10 affected198 at risk EG0020 events0 affected52 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG00070 events58 affected196 at risk EG00165 events52 affected198 at risk EG00212 events8 affected52 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG00046 events30 affected196 at risk EG00146 events34 affected198 at risk EG0022 events2 affected52 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG00095 events65 affected196 at risk EG001112 events77 affected198 at risk EG00215 events10 affected52 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0009 events9 affected196 at risk EG00111 events11 affected198 at risk EG0021 events1 affected52 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG00049 events34 affected196 at risk EG00152 events40 affected198 at risk EG0027 events7 affected52 at risk EG003
Asthenia	General disorders	MedDRA version 25.0	Systematic Assessment	EG00026 events20 affected196 at risk EG00129 events25 affected198 at risk EG0025 events4 affected52 at risk EG003
Chest discomfort	General disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events5 affected196 at risk EG0012 events2 affected198 at risk EG0022 events2 affected52 at risk EG003
Chest pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG00014 events14 affected196 at risk EG00122 events18 affected198 at risk EG0024 events4 affected52 at risk EG003
Fatigue	General disorders	MedDRA version 25.0	Systematic Assessment	EG00067 events51 affected196 at risk EG00166 events52 affected198 at risk EG0020 events0 affected52 at risk EG003
Oedema peripheral	General disorders	MedDRA version 25.0	Systematic Assessment	EG0008 events7 affected196 at risk EG00114 events13 affected198 at risk EG0020 events0 affected52 at risk EG003
Pyrexia	General disorders	MedDRA version 25.0	Systematic Assessment	EG00018 events16 affected196 at risk EG00132 events20 affected198 at risk EG0027 events4 affected52 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0023 events3 affected52 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0015 events4 affected198 at risk EG0024 events4 affected52 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG00020 events17 affected196 at risk EG00119 events15 affected198 at risk EG0022 events2 affected52 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0006 events6 affected196 at risk EG00118 events13 affected198 at risk EG0025 events5 affected52 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0009 events8 affected196 at risk EG00113 events10 affected198 at risk EG0021 events1 affected52 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0006 events6 affected196 at risk EG00113 events6 affected198 at risk EG00215 events10 affected52 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0007 events5 affected196 at risk EG0019 events8 affected198 at risk EG00216 events9 affected52 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected196 at risk EG0018 events8 affected198 at risk EG0024 events3 affected52 at risk EG003
Blood bilirubin increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0026 events5 affected52 at risk EG003
Blood cholesterol increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0024 events4 affected52 at risk EG003
Blood creatinine increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected196 at risk EG00113 events7 affected198 at risk EG0023 events3 affected52 at risk EG003
Blood glucose increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0023 events3 affected52 at risk EG003
Blood triglycerides increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0025 events4 affected52 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0024 events3 affected52 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0014 events1 affected198 at risk EG0024 events4 affected52 at risk EG003
Haemoglobin decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected196 at risk EG0011 events1 affected198 at risk EG0020 events0 affected52 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG00080 events45 affected196 at risk EG00174 events37 affected198 at risk EG00285 events33 affected52 at risk EG003
Platelet count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG00041 events30 affected196 at risk EG00138 events26 affected198 at risk EG00226 events14 affected52 at risk EG003
Protein urine present	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0024 events3 affected52 at risk EG003
Weight decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG00011 events10 affected196 at risk EG00121 events21 affected198 at risk EG0026 events6 affected52 at risk EG003
Weight increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0007 events6 affected196 at risk EG0013 events3 affected198 at risk EG0024 events4 affected52 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG00043 events24 affected196 at risk EG00135 events18 affected198 at risk EG00273 events29 affected52 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG00045 events41 affected196 at risk EG00164 events55 affected198 at risk EG00216 events12 affected52 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0011 events1 affected198 at risk EG0023 events3 affected52 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0007 events5 affected196 at risk EG00113 events9 affected198 at risk EG0023 events2 affected52 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG0020 events0 affected52 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected196 at risk EG0015 events3 affected198 at risk EG0025 events5 affected52 at risk EG003
Hypochloraemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events2 affected196 at risk EG0010 events0 affected198 at risk EG0027 events4 affected52 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG00018 events17 affected196 at risk EG0019 events9 affected198 at risk EG00210 events5 affected52 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG00010 events10 affected196 at risk EG00119 events13 affected198 at risk EG0023 events2 affected52 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG00014 events12 affected196 at risk EG00110 events10 affected198 at risk EG00217 events11 affected52 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected196 at risk EG0010 events0 affected198 at risk EG0024 events3 affected52 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG00029 events22 affected196 at risk EG00131 events25 affected198 at risk EG0024 events4 affected52 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG00020 events18 affected196 at risk EG00119 events19 affected198 at risk EG0020 events0 affected52 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0009 events8 affected196 at risk EG00113 events13 affected198 at risk EG0022 events2 affected52 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG00014 events11 affected196 at risk EG00123 events20 affected198 at risk EG0022 events2 affected52 at risk EG003
Headache	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG00026 events23 affected196 at risk EG00130 events25 affected198 at risk EG0023 events3 affected52 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG00014 events14 affected196 at risk EG00119 events16 affected198 at risk EG0029 events3 affected52 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected196 at risk EG0010 events0 affected198 at risk EG00210 events7 affected52 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG00033 events28 affected196 at risk EG00128 events22 affected198 at risk EG00212 events10 affected52 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG00018 events17 affected196 at risk EG00124 events21 affected198 at risk EG0022 events2 affected52 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG00012 events12 affected196 at risk EG00120 events14 affected198 at risk EG0026 events5 affected52 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0006 events5 affected196 at risk EG00117 events13 affected198 at risk EG0020 events0 affected52 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG00014 events9 affected196 at risk EG00110 events10 affected198 at risk EG0025 events5 affected52 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG00072 events69 affected196 at risk EG00175 events73 affected198 at risk EG00218 events18 affected52 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG00010 events9 affected196 at risk EG00117 events15 affected198 at risk EG0021 events1 affected52 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG00015 events13 affected196 at risk EG00125 events15 affected198 at risk EG0021 events1 affected52 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events2 affected196 at risk EG00111 events11 affected198 at risk EG0020 events0 affected52 at risk EG003
Hypertension	Vascular disorders	MedDRA version 25.0	Systematic Assessment	EG0008 events6 affected196 at risk EG00120 events15 affected198 at risk EG0022 events2 affected52 at risk EG003

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates