LBA22 - Effects of trastuzumab deruxtecan (T-DXd) vs choice of chemotherapy (TPC) on patient-reported outcomes (PROs) in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC): Results from DESTINY-Breast06

Background

DESTINY-Breast06, a randomized Phase 3 study, showed a progression-free survival benefit with T-DXd vs TPC in patients with hormone receptor–positive, HER2-low (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization−) and HER2-ultralow (IHC 0 with membrane staining) mBC. Here, we report the effect of T-DXd vs TPC on PROs in intent-to-treat (ITT; HER2-low + -ultralow) and HER2-low.

Methods

Patients with progressive disease (PD) after endocrine-based therapy (ET) and no prior chemotherapy for mBC were assigned 1:1 to T-DXd 5.4 mg/kg Q3W or TPC (59.8% capecitabine; 24.4% nab-paclitaxel; 15.8% paclitaxel). PRO instruments included the European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaire (QLQ-C30) and breast cancer-specific module (QLQ-BR45). Changes from baseline (CFB) and time to deterioration (TTD) were assessed.

Results

QOL data were similar in ITT and HER2-low. Median treatment duration was 11.0 (T-DXd) vs 5.6 (TPC) months (mo). Mean CFB (over 7 mo or until PD, whichever was earlier) were similar for T-DXd vs TPC for QLQ-C30 global health status (GHS)/QOL and functional items. Differences in some symptoms were observed between groups: T-DXd was associated with less pain (adjusted mean difference −7.2 [95% CI −9.9, −4.5]) and, for QLQ-BR45 items, fewer skin mucosis symptoms (−9.5 [−11.5, −7.5]), but more nausea/vomiting (7.2 [5.3, 9.2]) and appetite loss (6.8 [3.6, 10.0]) vs TPC (ITT). T-DXd reduced the risk of clinically meaningful deterioration in physical/role functioning and pain vs TPC (Table). Table: LBA22

CI, confidence interval; HR, hazard ratio; m, median; NR, not reached

Conclusions

T-DXd preserved QOL while delaying deterioration in physical/role functioning and pain vs TPC, albeit with more gastrointestinal symptoms. QOL data complement the efficacy/safety of T-DXd after ≥1 ET in patients with hormone receptor–positive, HER2-low/-ultralow mBC.

Clinical trial identification

NCT04494425.

Editorial acknowledgement

Under the guidance of the authors, medical writing support was provided by Georgina Stooke-Vaughan, PhD, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP) guidelines (http://www.ismpp.org/gpp-2022).

Legal entity responsible for the study

AstraZeneca and Daiichi Sankyo.

Funding

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

Disclosure

G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Editor of Chief of ESMO Open: ESMO; Non-Financial Interests, Leadership Role, Until the end of 2024: EUSOMA. K. Yonemori: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Genmab, Gliad, MSD, Novartis, OncoXerna, Sanofi, Takeda, Henlius, Ono, Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Bayer, Boehringer Ingerheim, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Fuji Film Pharma, Jansen, MSD, Ono, PDR Pharma, Pfizer, Sanofi, Takeda, Asteras, Merk Biopharma; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Coordinating PI: Genentech, Novartis, Pfizer, Merck, Sanofi, Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly, Menarini; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. C.H.E. Barrios: Financial Interests, Personal, Advisory Board, Consulting scientific presentations: Novartis, Pfizer, Roche, MSD, AstraZeneca, Lilly; Financial Interests, Personal, Advisory Board, Scientific Presentations Consulting AD Board: Daiichi Sankyio; Financial Interests, Personal, Invited Speaker, Consulting Scientific presentations: Gilead; Financial Interests, Personal, Ownership Interest, Virtual APP: THUMMI; Financial Interests, Personal, Stocks/Shares, clinical research company: MEDSIR; Financial Interests, Personal, Ownership Interest, Clinical Research Company: Centro de Pesquisa em Oncologia - CPO; Financial Interests, Institutional, Research Grant, research funding to the institution: Pfizer, Amgem, GSK, Lilly, Sanofi, Merk, Biomarin, BMS, Medivation, Exelixis, Merck KGAA, Shangai Henlius Biothech, Polyphor, Pharmamar; Financial Interests, Institutional, Research Grant, research funding to the institution Steering Committee: Novartis, AstraZeneca, Daiichi; Financial Interests, Institutional, Research Grant, research funding to the institution Steering committee: Roche; Financial Interests, Institutional, Local PI, Research funding to the institution: Nektar, Regeneron, Janssen, OBI Pharma, Seagen, Checkpoint Therapeutics, Novocure, Aveo Oncology, Takeda, Celgene, TRIO, PPD, Syneos health, DOCS, Labcorp, IQIVIA, Parexel, Nuvisan, PSI, Medplace; Financial Interests, Institutional, Local PI, Research funding to the institution Steering committee: Myovant; Non-Financial Interests, Member of Board of Directors, Member of Executive Board up to March 2023: BIG International Group; Non-Financial Interests, Leadership Role, Latin American Cooperative Oncology Group: LACOG; Non-Financial Interests, Other, Chair, International Educational Steering Group: ASCO; Non-Financial Interests, Advisory Role, Member Compliance Committee: ESMO. 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. C. Levy: Financial Interests, Personal, Speaker, Consultant, Advisor: Seagen, Gilead Sciences, Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Gilead Sciences, Pfizer. 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, Coordinating PI: Roche, Daiichi Sankyo; Financial Interests, Local PI: Roche, Novartis, Daiichi Sankyo. J. Tsurutani: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Eisai Inc., Daiichi Sankyo, Taiho Inc.; Financial Interests, Personal, Member of Board of Directors: West Japan Oncology Group; Financial Interests, Institutional, Research Grant: Eisai, Eli Lilly, Ono; Financial Interests, Institutional, Funding: Daiichi Sankyo, West Japan Oncology Group; Financial Interests, Institutional, Coordinating PI: FSJD. A. Roborel de Climens: Financial Interests, Personal, Full or part-time Employment, IQVIA employee: IQVIA; Financial Interests, Personal, Stocks/Shares, Holding Sanofi stocks/ shares: Sanofi; Non-Financial Interests, Advisory Role, Consultant reviewer of the abstract: AstraZeneca. X. Wu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Begbie: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Z. Mbanya: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: AstraZeneca. R.A. Dent: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Pfizer, Merck, Lilly, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Pfizer, Merck, Lilly; Financial Interests, Personal and Institutional, Trial Chair: Roche; Financial Interests, Personal, Steering Committee Member: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, Investigator Initiated Trial: AstraZeneca. All other authors have declared no conflicts of interest.