Keytruda’s Triumph in Early-Stage Triple-Negative Breast Cancer: A New Standard of Care

Keytruda’s Triumph in Early-Stage Triple-Negative Breast Cancer: A New Standard of Care

Merck’s Keytruda (pembrolizumab) has achieved a significant milestone in the fight against early-stage triple-negative breast cancer (TNBC), with new data demonstrating a substantial improvement in overall survival rates. This development follows an earlier controversy over its approval based on preliminary endpoints.

At the European Society for Medical Oncology (ESMO) 2024 annual meeting, Merck unveiled compelling results from the KEYNOTE-522 trial, which assessed Keytruda in combination with neoadjuvant chemotherapy before surgery and continued with adjuvant Keytruda after surgery. The results revealed a 34% reduction in the risk of death compared to chemotherapy alone in patients with high-risk nonmetastatic TNBC. The data, derived from a median follow-up of over six years, showed that 14.7% of patients receiving Keytruda had died, compared to 21.8% in the control group. The five-year overall survival rates were 86.6% for Keytruda versus 81.7% for the control arm.

This latest evidence bolsters Keytruda’s position as a gold-standard therapy for early-stage TNBC. The drug initially gained FDA approval in 2021 based on event-free survival (EFS) data, which demonstrated a 37% reduction in the risk of disease recurrence or progression compared to chemotherapy alone. However, this approval came after a previous rejection due to reliance on premature endpoints, including pathological complete response (pCR) and immature EFS data.

Despite this initial setback, the latest KEYNOTE-522 findings validate the efficacy of Keytruda in improving overall survival, aligning with its earlier EFS benefits. “We had thought that breast cancer might not be particularly responsive to immunotherapy alone,” noted Dr. Alessandra Curioni-Fontecedro, Director of Oncology at the Hospital of Fribourg, Switzerland. “However, combining it with chemotherapy both before and after surgery has shown a significant improvement in overall survival.”

The success of Keytruda contrasts sharply with Roche’s Tecentriq (atezolizumab). Tecentriq’s IMpassion030 trial, which evaluated the PD-L1 inhibitor in a similar setting, was halted due to lack of efficacy, and subsequent data showed a higher risk of recurrence or death compared to chemotherapy alone. The IMpassion031 trial, which also combined Tecentriq with chemotherapy, failed to show statistically significant improvements in EFS or overall survival.

Looking forward, Merck is advancing its efforts with the TroFuse-012 trial, exploring the combination of Keytruda with sacituzumab tirapazamine (sacituzumab-tetraxetan), an antibody-drug conjugate, to further enhance treatment outcomes. The trial, which began in June 2024, aims to enroll 1,530 patients and has an estimated completion date in late 2030.

The latest data underscores Keytruda’s transformative role in managing early-stage TNBC, setting a new standard for patient care and offering renewed hope for those affected by this aggressive cancer.