Dr LeVee on Limitations of the ASCENT-04 Trial of Sacituzumab Govitecan Plus Pembrolizumab in TNBC

“The trial included a small number of patients who [had] received prior PD-1 or PD-L1 therapy; the [number of] patients who had previously received pembrolizumab in the neoadjuvant or adjuvant setting was only [9].”

Alexis LeVee, MD, chief hematology and medical oncology fellow at City of Hope, discussed limitations of the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) findings in the context of patients with early-stage, locally advanced, unresectable or metastatic triple-negative breast cancer (TNBC) who had relapsed following prior PD-1 or PD-L1 therapy before receiving sacituzumab govitecan-hziy (Trodelvy), an antibody-drug conjugate (ADC), in combination with pembrolizumab (Keytruda).

The data generated in this specific patient subset remain inconclusive due to the small number of patients represented, LeVee began. Only 9 patients in ASCENT-04/KEYNOTE-D19 had previously received PD-1 or PD-L1–directed therapy in either the neoadjuvant or adjuvant setting, reflecting the increasing use of the phase 3 KEYNOTE-522 trial (NCT03036488) regimen of pembrolizumab plus chemotherapy as the standard of care for patients with early TNBC, she said. In forest plot analyses of ASCENT-04/KEYNOTE-D19, there was insufficient statistical power to meaningfully evaluate outcomes in this group, she noted. This limitation creates significant uncertainty regarding whether pembrolizumab should be reintroduced in the metastatic setting for patients who relapse after prior exposure, she added. The question of PD-1/PD-L1 inhibitor rechallenge remains open, and further data will be needed to clarify clinical decision-making in this scenario, according to LeVee.

The trial overall reinforced the growing role of ADCs in TNBC management, with sacituzumab govitecan demonstrating strong activity in combination with checkpoint inhibition, she stated. LeVee emphasized that ADCs are increasingly being tested earlier in the TNBC disease course, including in the neoadjuvant and adjuvant settings, where they may eventually displace or complement chemotherapy. Early signals suggest that ADC-based strategies may offer superior efficacy compared with traditional chemotherapy, aligning with broader efforts to refine and individualize treatment sequencing in breast cancer, she reported.