Oral Akynzeo® vs Standard of Care in Preventing CINV in H... | NCT04817189

Description Module

Detailed Description

Antiemetic guideline recommendations are based on the emetogenic potential of chemotherapy and involve 4 levels of classification of intravenous chemotherapy agents, i.e., high, moderate, low and minimal; these have been accepted by major organisations. Moderate emetogenic chemotherapy (MEC) results in acute vomiting in 30% to 90% of cancer patients in the absence of antiemetic therapy. In addition to the chemotherapy type, several patient-related risk factors and clinical characteristics can increase CINV risk. These can include use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, no complete CINV response in an earlier cycle, history of nausea/vomiting, (trait) anxiety, fatigue experience, and expectations of nausea/vomiting. Other studies have largely confirmed some of the key risk factors for CINV (history of vomiting during pregnancy, history of motion sickness, age, gender) and added other factors such as (chronic) alcohol consumption, body surface area, fewer hours slept the night prior to infusion, or advanced stage cancer. Currently, there is a limited consensus surrounding the most relevant patient risk factors that may predict CINV risk. Based on a recent study by Dranitsaris et al. eight predictive factors have been identified, and an algorithm has been developed to combine these patient-related risk factors into the optimal treatment of prophylactic antiemetics. These include:

nausea and/or vomiting in the prior cycle of chemotherapy
use of non-prescribed antiemetics at home in the prior cycle of chemotherapy
platinum or anthracycline-based chemotherapy
age < 60 years
expectations for (anticipating) nausea and/or vomiting
<7 h of sleep the night before chemotherapy
history of morning sickness during previous pregnancy
cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward).

Akynzeo®, an oral combination of the neurokinin 1 receptor antagonists (NK1 RA), netupitant and the 5-hydroxytryptamine (HT3) receptor antagonists (5-HT3 RA), palonosetron, is recommended by guidelines for the prevention of CINV. Akynzeo® has been evaluated in a multicentre, randomised, double-blind, double-dummy phase II clinical trial at various dose ranges among 694 cisplatin-treated cancer patients from 44 sites (two countries); each NEPA (netupitant-palonosetron) dose significantly improves CINV prevention in cancer patients. Similar results were obtained in another international, randomised, double-blind and parallel group phase III clinical trial; NEPA prevented CINV in patients receiving MEC.

The current study primarily aimed to evaluate whether Akynzeo® leads to a higher response rate compared with standard care in MEC regimen-treated patients who are identified to be at high risk based on the algorithm.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Experimental	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.	Drug: NEPA (300mg netupitant/0.5mg palonosetron) Drug: Dexamethasone, 8 mg (oral) or equivalent IV dose
Standard of care + Dexamethasone 8 mg	Active Comparator	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)	Drug: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV) Drug: Dexamethasone, 8 mg (oral) or equivalent IV dose

Interventions

Name	Type	Description	Arm Group Labels	Other Names
NEPA (300mg netupitant/0.5mg palonosetron)	Drug	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Probability of Complete Responses Over Three Cycles of Chemotherapy After the Start of the MEC Administration	To evaluate if the use of NEPA (netupitant and palonosetron) in patients treated with IV moderately emetogenic chemotherapy and at high risk of CINV is more effective in preventing CINV than a standard of care antiemetics over three cycles of chemotherapy. The primary endpoint is the probability of complete responses (no emetic episode and no rescue medication), during the overall phase (0-120h), after the start of the MEC administration over three cycles of chemotherapy. This endpoint is evaluated in patients with at least one reported cycle assessment. The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.	At the end of all three chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

Secondary Outcomes

Measure	Description	Time Frame
Evaluation of the Probability of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy	Probability of: No emetic episode during the acute, delayed, and overall phase and daily in each cycle No rescue medication during the acute, delayed, and overall phase and daily in each cycle No significant nausea (maximum MAT scale = 2) during the acute, delayed, and overall phase and daily in each cycle; No nausea (MAT scale = 0) during the acute, delayed, and overall phase and daily in each cycle; Complete protection (no emetic episode, no rescue medication, and no significant nausea) during the acute, delayed, and overall phase and daily in each cycle Time 0 is defined as the start time of the chemotherapy administration on Day 1 of each of the three cycles. The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult patients aged ≥18 years
Patients with a risk score of ≥ 13 as calculated by the algorithm - see 3.6.3.1. Baseline/screening: VISIT 0
Signed Informed consent
Both sexes
Patients with diagnosis of any cancer scheduled and intended to be treated for three consecutive cycles with a single dose of any IV MEC regimen, per cycle, including adjuvant or neo-adjuvant chemotherapy
Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Use of Standard of Care defined as a 5-HT3 RA + Dexamethasone (or equivalent corticosteroid) based-regimen on day 1 of chemotherapy for CINV prevention
Naïve and non- naïve to chemotherapy
The enrolled women should be a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test done by health care team within 1-24 hours before dosing the antiemetic treatment in both arms and outcome recorded in the medical records
Able to comply with study requirements

Exclusion Criteria:

Patients receiving highly emetogenic chemotherapy (including anthracycline+cyclophosphamide-based chemotherapy)
Patients receiving oral moderately emetogenic chemotherapy drugs
Patients receiving opioids within 2 weeks prior to trial enrollment (longer use allowed)
Use of olanzapine as prophylaxis of CINV
Patients scheduled to receive radiotherapy concurrently with chemotherapy
Any illness or condition that, in the opinion of the physician, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
Patients with mechanical risk factors for nausea (i.e. intestinal obstruction)
Patients with liver disease (as nausea is a common presenting symptom)
Patients with metabolic risk factors for nausea (i.e. electrolyte imbalances causing nausea/vomiting)
Chronic treatment with steroids (with the exception of inhaled or topical steroids)
Pregnancy and/or breast-feeding women
Women of childbearing potential refusing to use effective contraception during the whole study treatment and up to one month after study treatment with Akynzeo®
Use of Standard of Care including an NK-1 RA-based regimen to prevent CINV

Name	Affiliation	Role
Alex Molasiotis, prof.	University of Derby	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Shanghai Chest Hospital		Shanghai			China
Shanghai Ninth People´s Hospital

ID	Title	Description
FG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
FG001	Standard of care + Dexamethasone 8 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 5, 2024	Jul 17, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Probability of Complete Responses Over Three Cycles of Chemotherapy After the Start of the MEC Administration

To evaluate if the use of NEPA (netupitant and palonosetron) in patients treated with IV moderately emetogenic chemotherapy and at high risk of CINV is more effective in preventing CINV than a standard of care antiemetics over three cycles of chemotherapy.

The primary endpoint is the probability of complete responses (no emetic episode and no rescue medication), during the overall phase (0-120h), after the start of the MEC administration over three cycles of chemotherapy. This endpoint is evaluated in patients with at least one reported cycle assessment.

The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.

The Full Analysis Set (FAS) consists of 401 (NEPA: 196, SoC: 205) randomised patients to whom study drug was dispensed. It was the primary basis for the analyses of efficacy. Following the intent-to-treat principle, patients in the FAS population will be analysed according to the treatment to which they were randomised. The primary endpoint within the FAS was analysed based on data from 388 (NEPA: 189, SoC: 199) patients.

Posted

Number

Probability of complete response

At the end of all three chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle. NEPA (300mg netupitant/0.5mg palonosetron): Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone, 8 mg (oral) or equivalent IV dose: Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV) Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV): Standard of care will be administered on Day 1 of each cycle. Dexamethasone, 8 mg (oral) or equivalent IV dose: Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

Units	Counts
Participants	OG000189 OG001199

Title

Denominators

Categories

Title	Measurements
	OG0000.810 OG0010.718

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		generalized linear model		<0.05		Odds Ratio (OR)	1.67			2-Sided	95	1.12	2.49					Superiority		The model-based statistics were used to calculate the difference in the probability to experience a "per cycle" complete response between the treatment arms.

Secondary

Evaluation of the Probability of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy

Probability of:

No emetic episode during the acute, delayed, and overall phase and daily in each cycle
No rescue medication during the acute, delayed, and overall phase and daily in each cycle
No significant nausea (maximum MAT scale = 2) during the acute, delayed, and overall phase and daily in each cycle;
No nausea (MAT scale = 0) during the acute, delayed, and overall phase and daily in each cycle;
Complete protection (no emetic episode, no rescue medication, and no significant nausea) during the acute, delayed, and overall phase and daily in each cycle

Time 0 is defined as the start time of the chemotherapy administration on Day 1 of each of the three cycles.

The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.

The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms. The probability for the Standard of Care arm is reported as the crude probability in generic cycle. The probability for the NEPA arm was calculated as the derived probability based on model odds ratio, with the model including relevant covariates.

Posted

Number

Probability

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg

Secondary

Evaluation of the Predictive Role of Potential Risk Factors in the Development of CINV Over Three Cycles of Chemotherapy

Analysis of the development of CINV as a dependent variable will be performed to identify additional potential risk factors of CINV thought to be increasing the risk of CINV in patients receiving MEC.

The outcome measure is the development of CINV, defined as any occurrence of nausea or a vomiting episode.

The data on the development of CINV will be taken from data collection tools, patients' diaries and MASCC Antiemesis Tool (MAT).

The Full Analysis Set (FAS). Evaluation of the predictive role of potential risk factors within the FAS was analysed based on available data from 388 (NEPA: 189, SoC: 199) patients.

The number of patients included in the FAS population for each cycle depends on the availability of data on potential risk factors and the occurrence of nausea and/or vomiting. As the LOCF imputation method was applied for secondary endpoints, the number of participants analyzed in Cycle 1 remains lower.

Posted

Count of Participants

Participants

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg

Secondary

Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - the Frequency of Adverse Events (AE)

An overall summary of adverse events (AE) will be presented, including the frequency of patients with:

Any treatment-emergent adverse event
Any treatment-emergent adverse event related to a study drug
Any treatment-emergent adverse event leading to chemotherapy dose reductions or interruptions
Any treatment-emergent serious adverse event

All AEs will be summarized by their:

Severity
Seriousness
Relationship to a drug

Posted

Count of Participants

Participants

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - Percentage of Participants With Adverse Events

An overall summary of adverse events (AE) will be presented, including the percentage of patients with:

Any treatment-emergent adverse event
Any treatment-emergent adverse event related to a study drug
Any treatment-emergent adverse event leading to chemotherapy dose reductions or interruptions
Any treatment-emergent serious adverse event

All AEs will be summarized by their:

Severity
Seriousness
Relationship to a drug

Posted

Number

percentage of patients

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Number of Participants With Discontinuations Due to Adverse Events

The frequency of discontinuations due to adverse events (AE) will be presented.

Posted

Count of Participants

Participants

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Units	Counts

Secondary

Percentage of Participants With Discontinuations Due to Adverse Events

The percentage of patients with discontinuations due to adverse events (AE) will be presented.

Posted

Number

percentage of patients

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Units	Counts

Secondary

Number of Participants With Death Due to Adverse Events

The frequency of on treatment deaths due to adverse events (AE) will be presented.

Posted

Count of Participants

Participants

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Units	Counts
Participants

Secondary

Percentage of Participants With Death Due to Adverse Events

The percentage of patients with on treatment death due to adverse events (AE) will be presented.

All AEs leading to on treatment death will be summarized by their:

Severity
Seriousness
Relationship to a drug

Posted

Number

percentage of patients

At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Exploration of the Effect of CINV on Daily Activities and Quality of Life in Patients Receiving Moderately-emetogenic Chemotherapy Over Three Cycles of Chemotherapy

Evaluation of the effect of CINV on daily activities and quality of life that will be measured by using the Functional Living Index-Emesis (FLIE) questionnaire, a validated, nausea and vomiting specific, patient-reported outcome instrument.

The Functional Living Index-Emesis (FLIE) has 18 questions. These questions are divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18).

The minimum score for any question is 0 and the maximum score is 100. Higher scores indicate less impairment on daily life as a result of nausea or vomiting.

The model-based statistics of generalized linear model were used to calculate the difference in the score "per cycle" between the treatment arms.

Full analysis set. Patients with evaluable data in cycle 1 and eligible for imputation, using last observation carried forward (LOCF).

Posted

Mean

Standard Deviation

FLIE score

At the end of chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - Number of Days With Rescue Medication Administered for the Treatment of CINV

Health economic endpoint, the number of days with rescue medication administered for the treatment of CINV, will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Number of days

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - Daily Doses of Rescue Medication Administered for the Treatment of CINV

Health economic endpoint, the daily doses of rescue medication administered for the treatment of CINV, will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Doses of medication per cycle

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Number of Re-hydration Bags

Health economic endpoint, the number of re-hydration bags given for at least grade 2 vomiting (more details below), will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Number of bags

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Number of Days of Unplanned Hospitalisations

Health economic endpoint, the number of days of unplanned hospitalizations related to CINV, will be evaluated during the study cycles

All hospitalizations will be summarized according to the department of hospitalization (type of ward)

Posted

Mean

Standard Deviation

days of hospitalization

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Number of Outpatient Physician Visits

Health economic endpoint, the number of outpatient physician visits and health care consultations due to CINV (e.g., general practitioner), will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Number of outpatient visits

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Number of Unplanned Laboratory Test

Health economic endpoint, the number of unplanned laboratory test including those at unplanned hospitalizations due to CINV, will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Number of unplanned tests

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - Discontinuation of Chemotherapy Treatment Due to CINV

Health economic endpoint, the number of discontinuations of chemotherapy treatment due to CINV, will be evaluated during the study cycles

Posted

Count of Participants

Participants

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Number of Delays of Chemotherapy Administration Due to CINV

Health economic endpoint, the number of delays of chemotherapy administration due to CINV, will be evaluated during the study cycles.

Delays will be observed after the first administration of Cycle 1 for Cycles 2 and 3.

Posted

Count of Participants

Participants

At the start of cycles 2 and 3. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - the Average Length of Delay of Chemotherapy Administration Due to CINV

Health economic endpoint, the average length of delay (in days) of chemotherapy administration due to CINV, will be evaluated during the study cycles.

Delays will be observed after the first administration of Cycle 1 for Cycles 2 and 3.

Posted

Mean

Standard Deviation

Days

At the start of Cycles 2 and 3. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Secondary

Evaluation of Resource Utilization and Health Economic Outcome - Days of Absence From Work

Health economic endpoint, the number of days of absence from work, will be evaluated during the study cycles

Posted

Mean

Standard Deviation

Days

At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Units	Counts

Secondary

Evaluation of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy

Number of vomiting episodes during the acute, delayed, and overall phase in each cycle

Time 0 is defined as the start time of the chemotherapy administration on Day 1 of each of the three cycles.

The model-based statistics of generalized linear model were used to calculate the difference in the number of vomiting episodes "per cycle" between the treatment arms.

Full analysis set. Patients with evaluable data in cycle 1 and eligible for imputation, using last observation carried forward (LOCF).

Posted

Mean

Standard Deviation

Number of vomiting episodes

At the end of chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

ID	Title	Description
OG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle. NEPA (300mg netupitant/0.5mg palonosetron): Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone, 8 mg (oral) or equivalent IV dose: Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
OG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV) Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV): Standard of care will be administered on Day 1 of each cycle. Dexamethasone, 8 mg (oral) or equivalent IV dose: Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0006 affected196 at risk EG0015 affected205 at risk
Pancytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected196 at risk EG0015 affected205 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0003 affected196 at risk EG0011 affected205 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0013 affected205 at risk
Rectal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0011 affected205 at risk
Death	General disorders	Systematic Assessment	EG0002 affected196 at risk EG0012 affected205 at risk
Pyrexia	General disorders	Systematic Assessment	EG0003 affected196 at risk EG0011 affected205 at risk
General physical health deterioration	General disorders	Systematic Assessment	EG0001 affected196 at risk EG0011 affected205 at risk
Chills	General disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Pain	General disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Cholangitis	Hepatobiliary disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Cholangitis acute	Hepatobiliary disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Cholestasis	Hepatobiliary disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Hyper-transaminasaemia	Hepatobiliary disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Drug hypersensitivity	Immune system disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Infection	Infections and infestations	Systematic Assessment	EG0001 affected196 at risk EG0012 affected205 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0001 affected196 at risk EG0011 affected205 at risk
Abscess oral	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
COVID-19	Infections and infestations	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Catheter site infection	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Erysipelas	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Gastroenteritis salmonella	Infections and infestations	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Lower respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Ludwig angina	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Oxygen saturation decreased	Investigations	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Cerebrovascular accident	Nervous system disorders	Systematic Assessment	EG0002 affected196 at risk EG0011 affected205 at risk
Aphasia	Nervous system disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Cerebral artery occlusion	Nervous system disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Hemianopia	Nervous system disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0012 affected205 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Laryngospasm	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Antibiotic therapy	Surgical and medical procedures	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0001 affected196 at risk EG0010 affected205 at risk
Thrombosis	Vascular disorders	Systematic Assessment	EG0000 affected196 at risk EG0011 affected205 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0008 affected196 at risk EG0017 affected205 at risk
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0003 affected196 at risk EG0018 affected205 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected196 at risk EG0014 affected205 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0004 affected196 at risk EG0017 affected205 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00040 affected196 at risk EG00148 affected205 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG00041 affected196 at risk EG00129 affected205 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG00019 affected196 at risk EG00125 affected205 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00015 affected196 at risk EG00117 affected205 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0009 affected196 at risk EG0016 affected205 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0008 affected196 at risk EG0016 affected205 at risk
Abdominal discomfort	Gastrointestinal disorders	Systematic Assessment	EG0003 affected196 at risk EG00110 affected205 at risk
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0006 affected196 at risk EG0012 affected205 at risk
Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG0004 affected196 at risk EG0014 affected205 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0016 affected205 at risk
Eructation	Gastrointestinal disorders	Systematic Assessment	EG0005 affected196 at risk EG0012 affected205 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0005 affected196 at risk EG0011 affected205 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Hypoaesthesia oral	Gastrointestinal disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Abdominal distension Flatulence	Gastrointestinal disorders	Systematic Assessment	EG0004 affected196 at risk EG0011 affected205 at risk
Flatulence	Gastrointestinal disorders	Systematic Assessment	EG0000 affected196 at risk EG0014 affected205 at risk
Oral pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected196 at risk EG0014 affected205 at risk
Paraesthesia oral	Gastrointestinal disorders	Systematic Assessment	EG0000 affected196 at risk EG0014 affected205 at risk
Fatigue	General disorders	Systematic Assessment	EG00054 affected196 at risk EG00146 affected205 at risk
Asthenia	General disorders	Systematic Assessment	EG00025 affected196 at risk EG00121 affected205 at risk
General physical health deterioration	General disorders	Systematic Assessment	EG0003 affected196 at risk EG00112 affected205 at risk
Pain	General disorders	Systematic Assessment	EG0006 affected196 at risk EG0017 affected205 at risk
Pyrexia	General disorders	Systematic Assessment	EG0004 affected196 at risk EG0017 affected205 at risk
Oedema peripheral	General disorders	Systematic Assessment	EG0001 affected196 at risk EG0018 affected205 at risk
Chest pain	General disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Chills	General disorders	Systematic Assessment	EG0001 affected196 at risk EG0014 affected205 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG00023 affected196 at risk EG00130 affected205 at risk
Hypokalaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0005 affected196 at risk EG0013 affected205 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00011 affected196 at risk EG00116 affected205 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected196 at risk EG0017 affected205 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected196 at risk EG0017 affected205 at risk
Bone pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0007 affected196 at risk EG0013 affected205 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0006 affected196 at risk EG0012 affected205 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0003 affected196 at risk EG0014 affected205 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected196 at risk EG0012 affected205 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Paraesthesia	Nervous system disorders	Systematic Assessment	EG00033 affected196 at risk EG00126 affected205 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG00024 affected196 at risk EG00115 affected205 at risk
Neuropathy peripheral	Nervous system disorders	Systematic Assessment	EG00015 affected196 at risk EG00120 affected205 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00018 affected196 at risk EG00115 affected205 at risk
Hypoaesthesia	Nervous system disorders	Systematic Assessment	EG00011 affected196 at risk EG00120 affected205 at risk
Neurotoxicity	Nervous system disorders	Systematic Assessment	EG00010 affected196 at risk EG0018 affected205 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0008 affected196 at risk EG0017 affected205 at risk
Polyneuropathy	Nervous system disorders	Systematic Assessment	EG0006 affected196 at risk EG0017 affected205 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG0007 affected196 at risk EG0015 affected205 at risk
Cold dysaesthesia	Nervous system disorders	Systematic Assessment	EG0004 affected196 at risk EG0013 affected205 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0005 affected196 at risk EG0012 affected205 at risk
Taste disorder	Nervous system disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0004 affected196 at risk EG0018 affected205 at risk
Restlessness	Psychiatric disorders	Systematic Assessment	EG0002 affected196 at risk EG0014 affected205 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00010 affected196 at risk EG0014 affected205 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected196 at risk EG0018 affected205 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected196 at risk EG0016 affected205 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected196 at risk EG0011 affected205 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected196 at risk EG0011 affected205 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected196 at risk EG0014 affected205 at risk
Alopecia	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0009 affected196 at risk EG00112 affected205 at risk
Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 affected196 at risk EG0017 affected205 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0009 affected196 at risk EG0012 affected205 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0003 affected196 at risk EG0015 affected205 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected196 at risk EG0015 affected205 at risk
Peripheral coldness	Vascular disorders	Systematic Assessment	EG0005 affected196 at risk EG0014 affected205 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0002 affected196 at risk EG0015 affected205 at risk

ID	Title	Description
BG000	NEPA (300mg Netupitant/0.5mg Palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.
BG001	Standard of Care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)
BG002	Total	Total of all reporting groups

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000595957	netupitant, palosentron drug combination
D017829	Granisetron
D000077924	Palonosetron
D017294	Ondansetron
C060344	dolasetron
D000077526	Tropisetron
D003907	Dexamethasone
D000305	Adrenal Cortex Hormones

ID	Term
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D007191	Indazoles
D011720	Pyrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011812	Quinuclidines
D007546	Isoquinolines
D007093	Imidazoles
D002227	Carbazoles
D007211	Indoles
D006575	Heterocyclic Compounds, 3-Ring
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg	Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Dexamethasone (8 mg) will be administered on Day 1 of each cycle.	2	196	22	196	150	196
EG001	Standard of care + Dexamethasone 8 mg	Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either: Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)	2	205	23	205	150	205