217O - Patient-reported outcomes (PROs) from DESTINY-Breast04, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician's choice (TPC) in patients (pts) with HER2-low metastatic breast cancer (MBC)

Background

DESTINY-Breast04 (NCT03734029) showed improvement in progression-free and overall survival of T-DXd vs TPC in pts with HER2-low MBC regardless of hormone receptor status, with no new safety signals. Here we report PROs on the effect of treatment on health-related quality of life (QOL) of T-DXd vs TPC in the hormone receptor–positive cohort.

Methods

Pts with centrally confirmed HER2-low (IHC1+ or IHC2+/ISH-) MBC with 1-2 prior lines of chemotherapy in the metastatic setting were assigned 2:1 to T-DXd (Q3W) or TPC (Q3W or Q4W). PROs were measured using the European Organization for Research and Treatment of Cancer QOL questionnaires (EORTC QLQ-C30, primary variable: global health status [GHS]/QOL scale score, and EORTC QLQ-BR23) and the EuroQol 5-dimension, 5-level (EQ-5D-5L) visual analog scale (VAS). PROs were assessed at prespecified timepoints per the protocol. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. Deterioration was defined as an increase of ≥10 points.

Results

In both arms, compliance for questionnaires was >92% at baseline and >80% for cycles 2-27. Baseline GHS score was 36.3 for T-DXd and 37.8 for TPC. Mean CFB for GHS/QOL of the QLQ-C30 remained stable (within ± 10 points) over time for pts in the T-DXd arm (n=331) up to 27 cycles and TPC arm (n=163) up to 13 cycles; beyond these cycles, the number of pts on treatment (n<10%) was too low to be informative. Median TDD of QLQ-C30 GHS/QOL was 7.6 mo for T-DXd vs 5.1 mo for TPC (hazard ratio [HR], 0.71 [95% CI, 0.56-0.92]), and all prespecified QLQ-C30 subscales had longer TDD with T-DXd, including pain (HR, 0.51 [95% CI, 0.39-0.65]) and physical functioning (HR, 0.54 [95% CI, 0.42-0.70]). For breast-specific arm symptoms of the QLQ-BR23, median TDD was 9.8 mo for T-DXd vs 5.4 mo for TPC (HR, 0.67 [95% CI, 0.50-0.88]). Median TDD of EQ-5D-5L VAS was 8.8 mo for T-DXd vs 4.7 mo for TPC (HR, 0.70 [0.54-0.91]).

Conclusions

Pts who received T-DXd maintained GHS/QOL longer than TPC in all prespecified QLQ-C30 subscales while on therapy. These results are consistent with the primary results and confirm the QOL benefit of T-DXd vs TPC for pts with HER2-low MBC.

Clinical trial identification

NCT03734029.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Marianna B. Johnson, PhD, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

N.T. Ueno: Financial Interests, Personal, Advisory Role: DSI; Financial Interests, Personal, Other, Honoraria: DSI; Financial Interests, Personal, Research Grant: DSI. W. Jacot: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Daiichi Sankyo, Eisai, Lilly France, MSD, Novartis, Pfizer, Roche, Seagen; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca, Chugai Pharma, Eisai, Glaxo Smithkline, Lilly France, Novartis, Pfizer, Roche, Pierre Fabre, Sanofi Aventis; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo. T. Yamashita: Financial Interests, Personal, Other, Honoraria: Chugai, Eisai, Daiichi Sankyo, Novartis Pharma, Taiho, Nippon Kayaku, AstraZeneca, Kyowa kirin, Pfizer; Financial Interests, Institutional, Research Grant: Chugai, Taiho, Nippon Kayaku, Kyowa kirin. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim. E. Tokunaga: Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Eli Lilly, AstraZeneca. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, BMS, Puma, Oncolytics Biotech, MSD, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. J. Tsurutani: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Eisai Inc.; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo, Taiho Inc.; Financial Interests, Personal, Invited Speaker: West Japan Oncology Group; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Funding: Daiichi Sankyo, West Japan Oncology Group; Financial Interests, Institutional, Invited Speaker: FSJD. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. H.S. Rugo: Financial Interests, Personal, Other, Honoraria: Puma, Samsung, NAPO; Financial Interests, Institutional, Research Grant: Pfizer, Merck, Novartis, Lilly, Roche, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, Ayala, Astellas, Gilead. B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Eisai; Financial Interests, Institutional, Research Grant: Henrui. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers-Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GlaxoSmithKline, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC. Z. Mitri: Financial Interests, Personal, Advisory Board: Lilly, AstraZenica, Gilead; Financial Interests, Personal, Research Grant: Lilly, GSK, AstraZenica. R. Mahtani: Financial Interests, Personal, Advisory Board: Amgen, Agendia, AstraZeneca, Biotheranostics, Daiichi, Eisai, Genentech, Immunomedics, Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, Seagen. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Wang: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. D. Gambhire: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. F. Cottone: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Medscape, Art Tempi, Onkowissen, Gilead, Sanofi, Exact Sciences; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche, Sandoz-Hexal, Seagen, Aptitude Health, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Other, Founding Editor: BreastCare Journal. D.A. Cameron: Financial Interests, Institutional, Other, Consulting: Lilly, Novartis, Sanofi; Financial Interests, Institutional, Advisory Board: Roche, Grail, AstraZenica, Syntheon. S. Modi: Financial Interests, Personal, Other, Honoraria: Genentech, Daiichi Sankyo, AstraZeneca, Seattle Genetics, Novartis; Financial Interests, Personal, Advisory Board: Genentech, Daiichi Sankyo, AstraZeneca, Seattle Genetics, Macrogenics; Financial Interests, Personal, Speaker’s Bureau: Genentech, Seattle Genetics, Daiichi Sankyo; Financial Interests, Personal, Research Grant: Genentech, AstraZeneca, Seattle Genetics, Daiichi Sankyo.