192MO - DESTINY-Breast04 subgroup analyses of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with human epidermal growth factor 2 (HER2)-low, estrogen-receptor (ER) expression immunohistochemistry (IHC) 0-10% metastatic breast cancer (mBC)

Background

In the phase III DESTINY-Breast04 trial (NCT03734029), T-DXd significantly improved progression-free survival (PFS) and overall survival (OS) vs TPC in pts with HER2-low mBC regardless of hormone receptor expression. Breast cancers with low ER expression (IHC 1-10%) represent a subset of pts that may mimic the clinical behavior of triple-negative breast cancer. Here, we report analyses of pts with ER IHC 0% and 1-10%.

Methods

Pts with HER2-low (HER2 IHC 1+ or IHC 2+/ISH−) mBC who had been previously treated with 1 or 2 lines of chemotherapy were randomly assigned (2:1) to either T-DXd or TPC (physician’s choice of chemotherapy). Exploratory analyses of efficacy and safety, using the primary analysis data cutoff (Jan 11, 2022), were conducted for pts with ER IHC 0-10%.

Results

110 pts were included (ER IHC 0% n = 58; ER IHC 1-10% n = 52). Efficacy results are shown in the table. Pts with ER IHC 1-10% treated with T-DXd had longer PFS (median PFS, 8.4 months with T-DXd vs 2.6 months with TPC; hazard ratio, 0.24 [95% CI, 0.12-0.48]) and OS (hazard ratio, 0.35 [95% CI, 0.16-0.75]) vs TPC. In ER IHC 0-10% pts, the most common any-grade treatment-emergent adverse events (TEAEs; ≥20% of pts in either arm) were nausea, vomiting, fatigue, decreased appetite, alopecia, constipation, anemia, diarrhea, transaminases increased, white blood cell count decreased, and neutrophil count decreased. 40 (53.3%) and 24 (75.0%) pts in the T-DXd and TPC groups, respectively, experienced grade ≥3 TEAEs.

Table: 192MO

Efficacy in ER IHC 0% and ER 1-10% subgroups

CI, confidence interval; cORR, confirmed objective response rate; NE, not evaluable.¹Reported as hormone receptor-negative cohort in Modi S et al. N Engl J Med. 2022;387:9-20.

Conclusions

Efficacy, including survival, of T-DXd over TPC in pts with HER2-low ER 1-10% mBC was consistent with the outcomes observed in pts with HER2-low ER 0% mBC. T-DXd safety in the ER IHC 0-10% subgroup was manageable and consistent with the primary analysis.

Clinical trial identification

NCT03734029.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Katie Henderson, PhD, and Rachel Hood, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., and AstraZeneca.

Disclosure

D.A.A. Cameron: Financial Interests, Personal, Advisory Role, Consultancy: Seagen, Daiichi Sankyo, AstraZeneca, Synthon, Novartis, GSK. 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, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. T. Yamashita: Financial Interests, Personal, Invited Speaker, Honoraria: Chugai, Taiho, Nippon Kayaku, Kyowa Kirin, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Novartis, Eli Lilly; Financial Interests, Institutional, Research Grant: Chugai, Taiho, Nippon Kayaku, Kyowa Karin. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation; Other, Spouse - Employee: Roche. F. Zagouri: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Consultancy: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, Roche. 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. N. Harbeck: Financial Interests, Personal, Invited Speaker, Honoraria: Seagen, Roche, Pfizer, Pierre-Fabre, Novartis, MSD, Lilly, Gilead, Daiichi Sankyo, AstraZeneca, Amgen; Financial Interests, Personal, Advisory Role: Gliead, Sandoz, Seagen; Non-Financial Interests, Personal, Leadership Role: West Germany Study Group. R. Yerushalmi: Financial Interests, Personal, Invited Speaker: Roche, Teva, Medison, MSD, Astra-Zeneca; Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Astra-Zeneca, Gilead. Y. Lu: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Daiichi Sankyo, MSD, Novartis, Roche, Eli Lilly, Pfizer, Europharma, Eisai; Non-Financial Interests, Personal, Leadership Role, Co-Chair: MONALEESA7 steering committee; Non-Financial Interests, Personal, Advisory Role, Chair: RIGHT Choice steering committee; Financial Interests, Personal, Research Grant: AstraZeneca, MSD, Novartis, Roche, Pfizer; Financial Interests, Personal, Invited Speaker, Travel Expenses: Novartis, Roche; Financial Interests, Personal, Royalties: Taiwan. A. Gombos: Financial Interests, Personal, Invited Speaker, Honoraria: Lilly, Novartis; Financial Interests, Personal, Advisory Role, Consultancy: AstraZeneca, Seagen; Financial Interests, Personal, Invited Speaker, Travel & Expenses: AstraZeneca. C.M.A. Orbegoso, F. Cheng, L. Yung, R. Rajagopalan: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Tsurutani: Financial Interests, Personal, Invited Speaker, Honoraria: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Travel and Expenses: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. S. Modi: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Genentech, AstraZeneca, Seagen, Macrogenics; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Genentech, AstraZeneca, Seagen. All other authors have declared no conflicts of interest.