Abstract 188P
Background
In DESTINY-Breast04 (NCT03734029), 494 pts were assigned to T-DXd or treatment of physician’s choice (TPC), including CAP. Progression-free survival and overall survival favored T-DXd vs TPC in pts with HR+, HER2-low (immunohistochemistry 1+ or 2+/in situ hybridization negative) mBC. Still, CAP is often considered to have a smaller negative impact on HRQoL vs T-DXd. We report a HRQoL analysis of T-DXd vs CAP.
Methods
Before randomization into the DESTINY-Breast04 trial, a subgroup of 95 pts with HR+, HER2-low mBC were pre-assigned to CAP to ensure TPC arm assignment. At randomization, 61 of those pts were assigned to T-DXd and 34 pts to CAP (3-wk treatment cycles). PRO data were collected at prespecified timepoints during treatment using the European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ)-C30 and the breast cancer–specific EORTC QLQ-BR45 (scored as EORTC-QLQ-BR23). Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed.
Results
Survey compliance rate was >80% throughout treatment. Total patient-years of exposure was 49.1 for T-DXd and 16.4 for CAP. Baseline mean Global Health Status (GHS/QoL) score was 61.5 for T-DXd and 62.6 for CAP. Mean CFB for GHS/QoL was stable (within ±10 points) up to cycle 27 for T-DXd and cycle 21 for CAP, after which numbers of pts on treatment were too low for analysis. TDD hazard ratios for pain and arm symptoms favored T-DXd vs CAP; hazard ratios for the remaining scales were not significant. Table: 188P
TDD for prespecified scales from EORTC QLQ-C30 and QLQ-BR45
| Median (95% CI), months | T-DXd n = 61 | CAP n = 34 | T-DXd vs CAP Hazard ratio (95% CI) |
| QLQ-C30 | |||
| GHS/QoL | 13.1 (8.4-20.8) | 10.5 (3.5-15.5) | 0.68 (0.37-1.23) |
| Pain | 16.7 (10.9-NE) | 7.0 (1.5-10.5) | 0.42 (0.23-0.78) |
| Physical functioning | NE (13.1-NE) | 11.7 (4.2-NE) | 0.68 (0.34-1.34) |
| Emotional functioning | 21.7 (10.5-NE) | 11.7 (6.5-NE) | 0.89 (0.44-1.79) |
| Social functioning | 12.8 (5.6-NE) | 9.7 (4.7-NE) | 1.00 (0.54-1.84) |
| QLQ-BR45 | |||
| Breast symptomsa | NE (NE-NE) | NE (NE-NE) | 1.33 (0.43-4.14) |
| Arm symptoms | 11.5 (7.0-NE) | 5.1 (1.9-16.9) | 0.55 (0.30-0.99) |
NE, not estimable. aMedian (95% CI) not estimable due to low number of pts with deterioration events.
Conclusions
Despite the hypothesis that CAP would have a smaller negative impact on HRQoL vs T-DXd, mean CFB results were similar between the 2 treatment arms, and median TDD results suggest a slower worsening in pain and arm symptoms for T-DXd. While the sample size was small, these results support a benefit of T-DXd vs CAP for pts with HR+, HER2-low mBC.
Clinical trial identification
NCT03734029.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Alexandra Murphy, PhD, Katie Henderson, PhD, and Lauren Carroll, PhD, of ApotheCom.
Legal entity responsible for the study
Daiichi Sankyo, Inc., and AstraZeneca.
Funding
This study was funded by Daiichi Sankyo, Inc., and AstraZeneca. Medical writing support (ApotheCom) was funded by Daiichi Sankyo, Inc.
Disclosure
N.T. Ueno: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Daiichi Sankyo. F. Cottone: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo UK Ltd. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, IQVIA, Touchime; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers-Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; 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. T. Yamashita: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taiho, Nippon Kayaku, AstraZeneca, Kyowa kirin, Pfizer; Financial Interests, Institutional, Research Grant: Chugai, Taiho, Nippon Kayaku, Kyowa kirin; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Eli Lilly, Pfizer, AstraZeneca, Seagen, MSD. M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences, Veracyte, Guardant Health; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. N. Niikura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Daiichi Sankyo, Chugai, Eli Lilly, MSD; Financial Interests, Personal and Institutional, Research Grant: Chugai, Eisai, Nippon Kayaku; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo. F. Zagouri: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis Pharma, Roche, Gilead; Financial Interests, Personal, Principal Investigator: Daiichi Sankyo, Eli Lilly, AstraZeneca, Roche, Merck, MSD, Novartis, Pfizer. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Sanofi, Boehringer Ingelheim, Seagen; Financial Interests, Personal and Institutional, Other, Research Grant and Stock Option: Daiichi Sankyo. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, Exact Sciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. 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; Financial Interests, Personal, Officer, I am CSO in this non-profit: Translational Breast Cancer Research COnsortium; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech; Financial Interests, Institutional, Invited Speaker: Pfizer, Macrogenics, Genentech/Roche. Y. Tanabe Hashimoto: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo. J.H. Kim: Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Sanofi-Aventis, Roche diagnostics, Roche pharma, AstraZeneca; Financial Interests, Personal, Advisory Board, speaker at advisory board meeting: Everest Medicine; Financial Interests, Personal, Advisory Board: Yuhan, Pfizer, Roche Korea, Novartis, Eisai Co., Ltd., Daiichi Sankyo Korea, MSD Korea; Financial Interests, Institutional, Research Grant, Research grant for investigator-sponsored clinical trial (I am the coordinating PI): Ono Pharma Korea Co. Ltd.; Non-Financial Interests, Principal Investigator, Coordinating PI of Investigator sponsored clinical study - drug supplies from Roche: Roche. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. R. Bauer: Financial Interests, Personal, Stocks/Shares: Novo Nordisk; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. C. Orbegoso Aguilar: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. S. Modi: Financial Interests, Personal, Advisory Board, and invited speaker: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, Gilead; Financial Interests, Institutional, Sponsor/Funding: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, DualityBio, Nuvation; Financial Interests, Personal, Advisory Board: DualityBio. All other authors have declared no conflicts of interest.