An age-specific pooled analysis of trastuzumab deruxtecan (T‑DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.

person Ian E. Krop Yale Cancer Center, New Haven, CT info_outline Ian E. Krop, Hans Wildiers, Sara A. Hurvitz, Javier Cortes, Seock-Ah Im, Hiroji Iwata, Fabrice Andre, Cristina Saura, Shanu Modi, Sung-Bae Kim, Anton Egorov, Elton Mathias, Jillian Cathcart, Antonio Cagnazzo, Yingkai Cheng, Yeon Hee Park

Authors person Ian E. Krop Yale Cancer Center, New Haven, CT info_outline Ian E. Krop, Hans Wildiers, Sara A. Hurvitz, Javier Cortes, Seock-Ah Im, Hiroji Iwata, Fabrice Andre, Cristina Saura, Shanu Modi, Sung-Bae Kim, Anton Egorov, Elton Mathias, Jillian Cathcart, Antonio Cagnazzo, Yingkai Cheng, Yeon Hee Park Organizations Yale Cancer Center, New Haven, CT, University Hospital Leuven, Leuven, CA, Belgium, UCLA Hematology Oncology, Los Angeles, CA, International Breast Cancer Centre (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain, Seoul National University Hospital, Seoul, South Korea, Aichi Cancer Center Hospital, Aichi, Japan, Institut Gustave Roussy, Villejuif, France, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Memorial Sloan Kettering Cancer Center, New York, NY, Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center,, Seoul, Korea, Republic of (South), Daiichi Sankyo Inc., Basking Ridge, NJ, Samsung Medical Center, Seoul, South Korea Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Daiichi Sankyo Inc. and AstraZeneca Background: T-DXd is approved for use in pts with HER2+ unresectable or mBC after a prior anti-HER2-based regimen in the metastatic or (neo)adjuvant setting, based on the randomized phase 3 DESTINY-Breast03 study (Cortes et al. N Engl J Med 2022). Older pts with HER2+ mBC tend to have worse efficacy and safety outcomes, regardless of treatment (Evans et al. Cancer Res 2021). Outcomes of older pts treated with T-DXd have not been thoroughly examined. Here we report age-specific (<65 vs ≥65 years) efficacy and pooled safety analyses of T-DXd from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. Methods: DESTINY-Breast01 (data cutoff [DCO], March 26, 2021) and DESTINY-Breast02 (DCO, June 30, 2022) enrolled pts whose disease progressed on trastuzumab emtansine (T-DM1); DESTINY-Breast02 compared T-DXd to chemotherapy of physician’s choice. DESTINY-Breast03 (DCO, July 25, 2022) included pts previously treated with trastuzumab and taxane; pts received either T-DXd or T-DM1. Results: At baseline, there were 44 (23.9%), 85 (20.9%), and 49 (18.8%) pts ≥65 years of age who received T-DXd in DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, respectively. At DCO, median pooled treatment duration with T-DXd was 13.1 mo (range, 0.7-44.0) for pts <65 and 12.4 mo (range, 0.7-45.1) for pts ≥65. Key efficacy data are shown in the Table. Any-grade treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, and serious AEs were observed in 99.6%, 53.6%, and 24.3% of pts <65 and 100%, 65.5%, and 32.2% of pts ≥65, respectively. There were 125 (18.7%) and 45 (25.4%) TEAEs associated with T-DXd discontinuation in pts aged <65 and ≥65, respectively. Any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 11.8% of pts <65 and 17.5% of pts ≥65; grade 5 events occurred in 0.9% and 0.6% of pts <65 and ≥65, respectively. Additional efficacy and safety data will be presented. Conclusions: Results from this pooled analysis further demonstrate that T-DXd has a favorable benefit-risk profile in pts ≥65 years, with slightly increased toxicity, as expected. Clinical trial information: NCT03248492, NCT03523585, NCT03529110. DESTINY-Breast01 DESTINY-Breast01 DESTINY-Breast03 <65 (n=140) ≥65 (n=44) <65 (n=321) ≥65 (n=85) <65 (n=212) ≥65 (n=49) Median overall survival, mo (95% CI) 28.1 (23.3-36.1) 30.9 (21.9-NE) NR (35.5-NE) 30.2 (22.3-39.2) NR (40.5-NE) NR (26.3-NE) Median progression-free survival, mo (95% CI) 18.1 (13.8-NE) 19.4 (12.4-NE) 17.9 (14.1-20.8) 16.8 (12.7-NE) 30.4 (22.4-NE) 25.1 (14.1-37.3) Confirmed objective response rate by blinded independent central review, % (95% CI) 62.1 (53.6-70.2) 61.4 (45.5-75.6) 70.7 (65.4-75.6) 65.9 (54.8-75.8) 78.8 (72.6-84.1) 77.6 (63.4-88.2) Disease control rate, n (%) 136 (97.1) 43 (97.7) 296 (92.2) 82 (96.5) 205 (96.7) 47 (95.9) NE; not estimable; NR; not reached.