The invited discussant of the BEGONIA trial,1 Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, called the activity of the combination of durvalumab and datopotamab deruxtecan (Dato-DXd) “notable,” with a 74% response rate overall, regardless of PD-L1 status. “It would be interesting to know whether response differs according to TROP2 expression,” she said, noting that such analyses are presumably under way.
Mafalda Oliveira, MD, PhD
The safety profile of this combination is similar to that reported for Dato-DXd as a single agent, she noted. Nevertheless, stomatitis was “a frequent event,” seen in 69% of patients and leading to dose reductions in 14%. “Interestingly, this is not a common adverse event with other anti-TROP2 drugs such as sacituzumab govitecan-hziy,” she pointed out.
Other frequent toxicities with the combination included alopecia, nausea, constipation, fatigue, rash, and vomiting, but none were grade ≥ 3 except for stomatitis. “Given this adverse-event profile, it is important to know whether prophylactic therapy for stomatitis will be implemented moving forward and whether there are additional plans to mitigate this adverse event,” Dr. Oliveira commented.
‘Strong Rationale’ for Combination
Dr. Oliveira said the rationale for combining antibody-drug conjugates with immune checkpoint inhibitors is “strong” and warrants testing in triple-negative tumors, as is being done not just with Dato-DXd and T-DXd (fam-trastuzumab deruxtecan-nxki), but, for example, with ladiratuzumab vedotin. Ladiratuzumab vedotin in combination with pembrolizumab produced tumor reductions in 90% of patients as front-line therapy for advanced or metastatic triple-negative breast cancer in a phase Ib/II trial.2
Additional ongoing trials for some of these regimens are shown in -Table 1. Dr. Oliveira made the following prediction: “I believe that in the coming years, antibody-drug conjugates will change the landscape of the treatment of triple-negative breast cancer.”
DISCLOSURE: Dr. Oliveira reported financial relationships with Roche, GSK, Gilead, Puma Biotechnology, AstraZeneca, iTeos Therapeutics, Pierre-Fabre, MSD Novartis, and Eisai.
REFERENCES
1. Schmid P, Jung KH, Wysocki PJ, et al: Datopotamab deruxtecan + durvalumab as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer: Initial results from BEGONIA, a phase 1b/2 study. ESMO Breast Cancer Congress 2022. Abstract 166MO. Presented May 4, 2022.
2. Han HS, Diab S, Alemany C, et al: Open-label phase 1b/2 study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer. 2019 San Antonio Breast Cancer Symposium. Abstract PD1-06. Presented December 11, 2019.
