Dr Schmid on Key Efficacy Findings With Dato-DXd in Metastatic TNBC

Peter Schmid, FRCP, MD, PhD, professor, cancer medicine, centre lead, Centre of experimental Cancer Medicine, director, Barts Breast Cancer Centre, discusses key findings from the phase 1/2 BEGONIA trial (NCT03742102) in patients with unresectable, metastatic or locally advanced triple-negative breast cancer (TNBC), highlighting the clinical significance of these findings.

The BEGONIA trial is evaluating various combinations of the PD-L1 inhibitor durvalumab (Imfinzi) with other novel agents in the frontline setting in patients with advanced or metastatic TNBC. Findings from arm 7 of the trial, which evaluated datopotamab deruxtecan (Dato-DXd; DS-1062a) plus durvalumab in this patient population, were presented at the 2023 ESMO Congress.

Dato-DXd plus durvalumab elicited an overall response rate (ORR) of 79% (95% CI, 66.8%-88.3%), including 6 complete responses and 43 partial responses. Notably, investigators observed antitumor responses in patients regardless of PD-L1 expression level. In total, 87% of patients on arm 7 of BEGONIA had PD-L1–low or –negative disease, Schmid notes. Previously conducted phase 3 trials of chemotherapy plus immunotherapy in the first-line, metastatic TNBC setting have shown ORRs of approximately 40% to 45% in patients with PD-L1–negative tumors, Schmid explains. Therefore, the response rate seen with an antibody-drug conjugate plus an immune checkpoint inhibitor in this patient population is encouraging and warrants further evaluation, Schmid emphasizes. It is the highest ORR ever reported in a group of patients with first-line, metastatic TNBC with predominantly PD-L1–negative tumors, Schmid says.

Furthermore, early data from the BEGONIA trial demonstrate that the responses seen with Dato-DXd plus durvalumab are durable, with a median duration of response of 15.5 months (95% CI, 9.92–not calculable [NC]) and a median progression-free survival of 13.8 months (95% CI, 11.0-NC). In the future, this combination should be investigated in a randomized clinical trial setting, Schmid concludes. Arm 8 of the BEGONIA trial is currently enrolling and will evaluate Dato-DXd plus durvalumab in patients with PD-L1–high metastatic TNBC.

Editor’s Note: Dr Schmid reports honoraria from AstraZeneca, Daiichi, Gilead, Merck, Novartis, Pfizer, Roche, Sanofi, and Seagen; consulting or advisory roles with AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Daiichi, Eisai, Genentech, Gilead, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sanofi, and Seagen; and institutional research funding from Astellas Pharma, AstraZeneca, Genentech, Gilead, Medication Inc, Merck, Novartis, OncoGenex, and Roche.