The ORR is defined as the percentage (%) of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

The full analysis set (FAS) included all participants who were enrolled in the study and received at least 1 dose of treatment.

The PFS rate is the percentage of participants alive and free of disease progression at 12 months, estimated by the Kaplan-Meier method.

The FAS set included all the participants who were enrolled in the study and received at least 1 dose of treatment.

Survival rate is the percentage of participants alive at 12 months, estimated by the Kaplan-Meier method.

The FAS included all participants who were enrolled in the study and received at least 1 dose of treatment.

The ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, as determined by ICR per RECIST 1.1.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment.

Duration of response is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by ICR or death due to any cause.

The FAS included all participants who were enrolled in the study and received at least 1 dose of treatment.

Time to progression by RECIST 1.1 per ICR is defined as the time from the date of the first dose of study intervention to the date of documented disease progression.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment.

Duration of treatment on subsequent therapy is defined as the time from the date of first dose of a subsequent therapy until date of the last dose of that therapy.

The Full analysis set-subsequent therapy included all participants in FAS had RECIST progression, as assessed by investigator, during the study and received subsequent anti-cancer therapy. The "number analyzed" refers to the number of participants included in analysis in specific time points in each row.

Second progression-free survival rate is the percentage of participants alive and free from a second progression on next-line treatment at 12 months, estimated by the Kaplan-Meier method. The second progression is defined as the earliest progression event subsequent to the first anti-cancer therapy after the initial progression.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment.

The incidence rate is defined as proportion of participants with new symptomatic CNS metastases during treatment period in participants without symptomatic CNS metastasis at baseline.

The FAS included all the participants who were involved in the study and received at least 1 dose of treatment.

The time to next progression is defined as the time from the date of the first documented isolated CNS progression to the date of the next documented disease progression (CNS or extracranial) per RECIST 1.1 or death and has been summarized descriptively in participants who have developed isolated CNS progression, receive local therapy, and continue on protocol therapy.

The FAS for isolated CNS progression analyses included participants that received at least 1 dose of treatment who developed isolated CNS progression, per investigator assessment, received local therapy, and continued on protocol therapy.

Site of next progression (CNS [CNS RECIST 1.1] or extracranial [systemic RECIST 1.1] in participants who developed isolated CNS progression, received local therapy, and continued on protocol therapy.

The FAS for isolated CNS progression analyses included participants that received at least 1 dose of treatment who developed isolated CNS progression, per investigator assessment, received local therapy, and continued on protocol therapy.

Central nervous system progression free survival rate is the percentage of participants free from central nervous system progression at 12 months, estimated by the Kaplan-Meier method.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment.

The time to new CNS lesions is defined as the time from the date of the first dose of study intervention to the date of documented new CNS lesions by RECIST 1.1 per ICR.

The FAS included all participants who were enrolled in the study and received at least 1 dose of treatment.

The CNS ORR is defined as the percentage of participants with measurable brain metastasis at baseline who have a confirmed CR or confirmed PR of brain lesions, as determined by ICR per CNS RECIST 1.1.

The FAS included all participants who were enrolled in the study and received at least 1 dose of treatment. Here, number of participants analyzed represents participants who had measurable CNS disease at baseline.

The CNS DoR is defined as the time from the date of first documented confirmed CNS response until date of documented CNS progression per CNS RECIST 1.1 as assessed by ICR or death due to any cause.

The FAS included all participants who were enrolled in the study and received at least 1 dose of treatment.

The EORTC QLQ-C30 is a 30-item questionnaire for cancer assessment. Increased scores indicate improvement; decreased scores indicate deterioration. Physical function: ≥+9= improvement, ≤-10=deterioration, otherwise=no change; Role functioning: ≤-6=deterioration, otherwise=no change; Social functioning: ≥+8=improvement, ≤-7=deterioration, otherwise=no change; Cognitive functioning: ≥+ 5=improvement, ≤- 4=deterioration, otherwise=no change; Global Health Status: ≥+2=improvement, ≤-8=deterioration, otherwise=no change; Fatigue: ≥+8=improvement, ≤-8=deterioration, otherwise=no change; Nausea and vomiting: ≤-11=deterioration, otherwise=no change; Appetite loss: ≤-14=deterioration, otherwise=no change; rest of scales: ≥+10=improvement, ≤-10=deterioration, otherwise=no change. Best on treatment response is best response category (improvement, no change, and deterioration) achieved by participants between first dose and 47 days after last dose, and prior to starting any anticancer therapy.

The safety analysis set included all the participants who have received at least 1 dose of treatment. The "overall number of participants analyzed" represents only participants who were not missing baseline data. The "number analyzed" refers to the number of participants included in each row for each response category.

The NANO scale is a clinician-reported assessment of neurologic functioning in neuro-oncology participants. The instrument captures 9 domains (gait, strength, ataxia, sensation, visual fields, facial strength, language, level of consciousness, and behavior) and was developed to provide a simple, objective assessment of neurologic function that would be combined with radiographic assessment to provide an overall outcome assessment for neuro-oncology participants in clinical trials and in daily practice. The soring scale for Gait consists of score range 0-3, Strength consists of score range 0-2, ataxia (upper extremity) consists of scale range 0-2 and sensation as 0. Higher scores indicate worse neurologic function. The response categories reported are changes from first post-baseline score to worst on-treatment score at any point of treatment.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment.

The PAL is a computerized, self-completed cognitive test used to capture cognitive function, including attention, memory, and executive function. This gamified test included PAL and was a low-burden, highly sensitive, precise measure of cognitive function. The PALFAMS is the number of times a participant chose the correct box on their first attempt when recalling the pattern locations, calculated across all assessed trials. A higher number of events of selecting correct boxes indicates better cognitive function. Here, baseline was the last non-missing value prior to administration of the first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The PAL is a computerized, self-completed cognitive test used to capture cognitive function, including attention, memory, and executive function. This gamified test included PALTEA and was a low-burden, highly sensitive, precise measure of cognitive function. PALTEA is the number of times a participant chose the incorrect box for a stimulus on assessment problems, plus an adjustment for the estimated number of errors they would have made on any problems, attempts, and recalls they did not reach. A higher number of events of selecting incorrect boxes indicates worse cognitive function. Here, baseline was the last non-missing value prior to administration of the first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

This is a computerized, self-completed cognitive test used to capture cognitive function, including attention, memory, and executive function. This gamified test included Reaction Time Task (RTI) and was low-burden, highly sensitive, precise measures of cognitive function. RTI Median Five-Choice Movement Time: median time taken for a participant to release response button and select target stimulus after it flashed yellow on screen. Calculated across correct, assessed trials in which stimulus could appear in any one of five locations. RTI Median Five-Choice Reaction Time: median duration it took for a participant to release response button after presentation of target stimulus. Calculated across correct, assessed trials in which stimulus could appear in any one of five locations. Measured in milliseconds. Higher reaction times indicate worse cognitive function. Here, baseline was the last non-missing value prior to administration of the first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The SWM is a computerized cognitive test. The SWM Between Errors (SWMBE) is number of times a participant incorrectly revisits a box in which a token has previously been found, calculated across all 4, 6, and 8 token trials. SWM Between Errors 4 Boxes (SWMBE4), SWM Between Errors 6 Boxes (SWMBE6), and SWM Between Errors 8 Boxes (SWMBE8) are number of times a participant revisits a box in which a token has previously been found. These are calculated across all trials with 4 tokens only for SWMBE4, 6 tokens only for SWMBE6, and 8 tokens only for SWMBE8. SWM Total Errors is number of times a box is selected that is certain not to contain a token and therefore should not have been visited by participant. A higher number of incorrect revisit events to previously found token boxes indicates worse cognitive function, and a lower number of revisit events indicates better cognitive function. Here, baseline was last non-missing value prior to administration of first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The SWM is a computerized cognitive test. The SWMS, the number of times a participant restarted search patterns from the same initial box, indicating their use of a planned strategy to find tokens. An increased number of events where search patterns started from the same initial box suggested participants were using a planned strategy to find tokens, which indicated better cognitive function. Here, a low score indicated high strategy use (1 = they always began the search from the same box). Conversely, high scores represented a decrease in events of beginning searches from the same box. Instead, starting from many different boxes suggested the participant was not using a consistent strategy, which indicated worse cognitive function. This was calculated across assessed trials with 6 tokens or more. Here, baseline was the last non-missing value prior to administration of the first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The effect of T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline brain metastasis was evaluated. The SGRQ-I is an idiopathic pulmonary fibrosis-specific version of the instrument developed and validated for use among participants with idiopathic pulmonary fibrosis, a type of ILD. The SGRQ-I was used to assess the HRQoL among participants who have been diagnosed with ILD/pneumonitis. It includes 34 of the original SGRQ items determined to be most reliable for assessing the HRQoL of participants with idiopathic pulmonary fibrosis. The instrument yields 3 domain scores (symptoms, activity, and impact) as well as a total score, with scores ranging from 0 to 100. Higher scores indicate greater impairment in HRQoL.

The safety analysis set- ILD consisted of participants who developed ILD/Pneumonitis. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The T-DXd on symptoms, functioning, and HRQoL in HER2+ MBC participants with or without baseline brain metastasis was evaluated. The MDASI brain tumor module includes 9 symptoms specific to brain tumors (weakness on one side of the body, difficulty understanding, difficulty speaking, seizures, difficulty concentrating, problems with vision, change in appearance, change in bowel pattern (diarrhea or constipation), and irritability). These 9 items will be used to capture symptoms associated with brain metastasis for those diagnosed with brain metastasis. Each item is rated on an 11-point numeric rating scale on a scale of 0-10, with higher scores indicating greater symptom severity. Here, baseline was the last non-missing value prior to administration of the first dose of study intervention.

The FAS included all the participants who were enrolled in the study and received at least 1 dose of treatment. The "number analyzed" refers to the number of participants included in the analysis at specific time points in each row.

The safety and tolerability of the participants who received T-DXd was evaluated.

SAE=Serious adverse events; CTCAE=Common Terminology for Adverse Events

The Safety analysis set included all participants who had received at least 1 dose of treatment.

The number of participants with ILD/Pneumonitis were by grouped term based on Investigator-reported preferred terms. No adjudication was performed.

The Safety analysis set consisted of all participants who had received at least 1 dose of treatment.

The number of participants with ILD clinical symptoms resolution in ILD/Pneumonitis participants who have been treated with high dose steroid (>2 mg dexamethasone) were evaluated.

The Safety analysis set-ILD consisted of all participants who had developed ILD/Pneumonitis. Here, the "overall number of participants analyzed" represents those who were treated with a high dose of steroids. Participants could have multiple ILD events with different statuses.