Dr Vahdat on Recent Data on ADCs in Metastatic TNBC

Linda Vahdat, MD, MBA, professor of medicine, Geisel School of Medicine at Dartmouth, section chief, Medical Oncology, interim section chief, Hematology, Dartmouth Cancer Center, discusses recent clinical trial data for antibody-drug conjugates (ADCs) being evaluated in patients with metastatic triple-negative breast cancer (TNBC), highlighting sacituzumab tirumotecan (SKB264/MK-2870) and enfortumab vedotin-ejfv (Padcev).

Sacituzumab tirumotecan, an ADC targeting TROP-2, has a belotecan payload, which is a novel topoisomerase I inhibitor. The agent was evaluated vs physician’s choice of chemotherapy in the phase 3 OptiTROP-Breast01 study (NCT05347134) in patients with locally recurrent or metastatic TNBC that was relapsed/refractory to at least 2 chemotherapy regimens for unresectable, locally advanced, or metastatic disease.

Findings from the trial’s interim analysis presented at the 2024 ASCO Annual Meeting showed that at a median follow-up of 5.1 months, patients treated with sacituzumab tirumotecan (n = 130) achieved a median progression-free survival (PFS) of 5.7 months (95% CI, 4.3-7.2) compared with 2.3 months (95% CI, 1.6-2.7) for those in the chemotherapy group (n = 133) per blinded independent central review assessment (HR, 0.31; 95% CI, 0.22-0.45; P < .00001). In the final PFS analysis at the median follow-up of 10.4 months, the median PFS was 6.7 months (95% CI, 5.5-8.0) for the sacituzumab tirumotecan arm vs 2.5 months (95% CI, 1.7-2.7) for the chemotherapy arm (HR, 0.32; 95% CI, 0.22-0.44; P < .00001).

Additionally, an interim analysis for overall survival (OS) at a median follow-up of 10.4 months showed that the median OS was not reached (95% CI, 11.2–not evaluable [NE]) in the sacituzumab tirumotecan arm vs 9.4 months (95% CI, 8.5-11.7) in the chemotherapy arm (HR, 0.53; 95% CI, 0.36-0.78; P = .0005).

The phase 2 EV-202 study (NCT04225117) investigated enfortumab vedotin in patients with advanced solid tumors, including hormone receptor–positive, HER2-negative breast cancer and TNBC.

Findings from the TNBC cohort presented at the 2024 ASCO Annual Meeting showed that evaluable patients (n = 42) experienced an overall response rate of 19.0%; however, Vahdat acknowledges that the disease control rate (DCR) was 57.1%. At a median follow-up of 11.76 months, the median OS was 12.91 months (95% CI, 10.28-NE]. Vahdat emphasizes the need for further research on enfortumab vedotin, given its potential benefit in this challenging treatment landscape.