186O - Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC)

Background

In DESTINY-Breast02 (NCT03523585), T-DXd improved progression-free and overall survival vs TPC in pts with HER2+ mBC who were resistant/refractory to trastuzumab emtansine (T-DM1) (Krop et al. SABCS 2022). Here, we report data on PROs and health-related quality of life (QoL).

Methods

Pts with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization amplified) T-DM1–resistant/refractory mBC were assigned 2:1 to T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine). PROs were collected and measured at prespecified timepoints using the European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ)-C30, the breast-cancer–specific EORTC QLQ-BR45 (scored as EORTC QLQ-BR23), and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. QLQ-C30 global health status (GHS)/QoL score was the primary variable of interest.

Results

In the T-DXd (n = 406) and TPC (n = 202) arms (median treatment duration of the safety analysis set: 11.3 vs ∼4.5 mo), questionnaire compliance was >92% at baseline and >76% at cycles 3-29. Mean CFB of GHS/QoL remained stable (within ±10 points) up to cycle 39 for T-DXd and cycle 21 for TPC, after which the number of pts on treatment was not informative (n < 10%). Median TDD was longer with T-DXd vs TPC for GHS/QoL (14.1 vs 5.9 mo; HR, 0.56 [95% CI, 0.44-0.71]) and for all measured QLQ-C30 subscales, including physical functioning (18.7 vs 6.8 mo; HR, 0.46 [95% CI, 0.36-0.60]) and pain (18.7 vs 5.8 mo; HR, 0.38 [95% CI, 0.29-0.49]), with the exception of nausea/vomiting (5.7 vs 6.1 mo; HR, 1.09 [95% CI, 0.86-1.39]). With T-DXd vs TPC, pts experienced prolonged TDD on the QLQ-BR23 arm symptom subscale (18.3 vs 8.8 mo; HR, 0.57 [95% CI, 0.44-0.75]).

Conclusions

Mean CFB in GHS/QoL suggested that overall health and QoL were maintained in T-DXd-treated pts. TDD was longer on all measured QLQ-C30 subscales, except for nausea/vomiting, for pts receiving T-DXd vs TPC. These results continue to support the benefit of T-DXd in pts with T-DM1–resistant HER2+ mBC.

Clinical trial identification

NCT03523585.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Caylin Bosch, PhD, and Toinette Labuschagné, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

This study was funded by Daiichi Sankyo, Inc., and AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).

Disclosure

T.N. Fehm: Financial Interests, Personal, Other, Honoraria: Onkowissen, Medconcept; Financial Interests, Institutional, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Roche, Stemlines, MSD, Pierre Fabre, AstraZeneca. F. Cottone, K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: MEDIMMUNE, Gilead, Relay therapeutics; Other, Founder: Pegacsy. I. Krop: Financial Interests, Personal, Advisory Board: Genentech/Roche, AstraZeneca, Daiichi Sankyo, Macrogenics, Seagen; Financial Interests, Personal, Other, DSMB member: Novartis; Financial Interests, Personal, Other, DSMC member: Merck; Financial Interests, Personal, Full or part-time Employment, Spouse: PureTech, Freeline; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech, Freeline; Financial Interests, Institutional, Invited Speaker: Pfizer, Macrogenics, Genentech, Roche. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Lilly, MSD, Eisai, Roche, Daiichi Sankyo, Menarini, Bixink; Financial Interests, Personal, Research Grant: MSD, AstraZeneca, Roche, Pfizer, Novartis; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Lilly, MSD, Daiichi Sankyo, AstraZeneca, Pfizer, Menarini, GSK, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Roche, Eli Lilly, MSD, Daiichi Sankyo, AstraZeneca, GSJ, Menarini, Gilead, Seagen. Y. Miyoshi: Financial Interests, Personal, Speaker’s Bureau: Chugai, Eli Lilly, Daiichi Sankyo, Taiho, MAD, Kyowa-Kirin, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai, Eli Lilly, Daiichi Sankyo, Taiho, MAD, Kyowa-Kirin, Eisai, AstraZeneca. A. Armstrong: Financial Interests, Personal, Advisory Board: MSD, Gilead; Financial Interests, Personal, Stocks/Shares, Spouse Shares: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other, Travel: MSD, Gilead; Financial Interests, Invited Speaker, Travel: Novartis. R. Yerushalmi: Financial Interests, Personal, Invited Speaker: Roche, Teva, Medison, MSD, Astra-Zeneca; Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, AstraZeneca, Gilead. F.P. Duhoux: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Lilly, AstraZeneca, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre; Financial Interests, Personal, Other, Travel: Daiichi Sankyo, Gilead, Pfizer, Roche; Financial Interests, Personal, Research Grant: Fondation Belge contre le Cancer. T. Takano: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Chugai, Eli Lilly. W. Lu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. C. Livings: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Egorov: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, Beigene, HLB Life Science, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks, Neogene TC; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. All other authors have declared no conflicts of interest.