Multinational phase 1b-2 trial of first-line durvalumab plus T-DXd for advanced HR-negative, HER2-low breast cancer: arm 6 of BEGONIA

More effective therapies are required for advanced breast cancer. In arm 6 of the mulitnational phase 1b-2 BEGONIA platform trial, 58 women with locally advanced unresectable or metastatic HR-negative, HER2-low breast cancer received durvalumab (1,120 mg) plus trastuzumab deruxtecan (T-DXd; 5.4 mg/kg) intravenously every three weeks as first-line treatment. Primary endpoints were objective response rate (ORR) and safety. The median duration of follow-up was 20.6 months (range 1-37). The median number of doses was 14.5 (range 1-43) for durvalumab and 13.0 (1-43) for T-DXd; median treatment duration was 11 months (1-32) and 10 months (1-32), respectively. The median ORR was 62.1% (95% CI 48.4-74.5), which did not meet the protocol-specified objective of 66.6%. Median duration of response was 15.2 months (95% CI 8.44-NC), whereas median progression-free survival and overall survival were 12.6 months (8.4-16.3) and 30.3 months (18.8-NC). The safety profile of the combination treatment was consistent with the known safety profiles of the individuals drugs. The authors conclude that durvalumab plus T-DXd demonstrated clinically relevant efficacy as first-line treatment of advanced HR-negative, HER2-low breast cancer.