New Combination Therapy for PD-L1 Positive TNBC Shows Promising Results in Clinical Trial Published in NEJM

New Combination Therapy for PD-L1 Positive TNBC Shows Promise

Gilead Sciences has announced significant results from the ASCENT-04/KEYNOTE-D19 trial published in the New England Journal of Medicine. The study evaluated the combination therapy of Trodelvy (sacituzumab govitecan) and Keytruda (pembrolizumab) for the first-line treatment of PD-L1 positive metastatic triple-negative breast cancer (TNBC). The results indicated a 35% reduction in the risk of disease progression or death compared to standard treatment with Keytruda and chemotherapy.

Trial Overview

The phase III ASCENT-04 trial included 443 patients with PD-L1 positive, unresectable locally advanced or metastatic TNBC, who were randomly assigned to receive either the combination of Trodelvy and Keytruda or standard chemotherapy with Keytruda. With a median progression-free survival (PFS) of 11.2 months for the combination therapy versus 7.8 months for the chemotherapy group, the new regimen demonstrated notable efficacy.

Expert Insights

Dietmar Berger, Chief Medical Officer of Gilead, emphasized the urgent need for effective treatment options in this challenging patient population, stating, "The results represent a vital advancement towards our goal of delivering Trodelvy to early-stage breast cancer patients and hold potential to become the foundational treatment for those in need."

The lead investigator of the ASCENT-04 trial, Dr. Sara Tolaney from Dana-Farber Cancer Institute, remarked on the significance of the findings, highlighting that current treatment options for PD-L1 positive metastatic TNBC remain limited. She noted the promising results could lead to a new standard of care in managing this aggressive disease.

Safety Profile

The safety profile of the Trodelvy and Keytruda combination therapy was consistent with the known profiles of both agents, with no new safety signals identified. Most common grade 3 adverse events included neutropenia (43%) and diarrhea (10%), while treatment discontinuation due to adverse events was lower in the combination group (12%) compared to the chemotherapy group (31%).

Trodelvy has already established its use among healthcare providers, being administered to over 60,000 patients across more than 50 countries, primarily for previously treated metastatic TNBC. It is the only antibody-drug conjugate (ADC) with significant evidence for survival benefit in patients with metastatic TNBC and specific cases of hormone receptor-positive breast cancer.

Future Implications

The announcement in NEJM follows the upcoming presentations planned for the 2025 annual meeting of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO). Gilead is also preparing to submit additional applications to the FDA and European Medicines Agency (EMA) regarding both indications.

Overall, the results from the ASCENT-04 trial not only offer hope to patients suffering from a challenging subtype of breast cancer but also pave the way for innovative treatment approaches that could redefine standards of care in oncology. As the research progresses, the landscape of TNBC treatment may witness a shift that incorporates these potentially more effective therapies.