Try our mobile app
First Approval for KEYTRUDA in the Breast Cancer Setting
KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-approved test. The approval is based on results from the Phase 3 KEYNOTE-355 trial, where KEYTRUDA in combination with chemotherapy – paclitaxel (pac), paclitaxel protein-bound (commonly known as nab-paclitaxel) or gemcitabine (gem) and carboplatin (carbo) – significantly reduced the risk of disease progression or death by 35% for patients whose tumors express PD-L1 (CPS ≥10) versus the same chemotherapy regimens alone (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012). Events were observed in 62% (n=136/220) of these patients receiving KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo versus 77% (n=79/103) with the same chemotherapy regimens alone. In the trial, 38% of patients had tumors expressing PD-L1 with CPS ≥10. This indication is approved under accelerated approval based on progression-free survival (PFS); continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
“Approximately 15-20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer,” said Dr. Hope Rugo, director of Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. “Notably, in KEYNOTE-355, KEYTRUDA was combined with three different chemotherapy regimens: paclitaxel, nab-paclitaxel or gemcitabine and carboplatin. The approval of KEYTRUDA in combination with chemotherapy gives physicians an important new option for appropriate patients.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.
“Today’s approval is a significant milestone, as it represents the first approval for KEYTRUDA in the breast cancer setting,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “In the study supporting this approval, KEYTRUDA in combination with paclitaxel, nab-paclitaxel or gemcitabine and carboplatin significantly improved progression-free survival for patients with advanced triple-negative breast cancer whose tumors express PD-L1 with CPS greater than or equal to 10 compared with the same chemotherapy regimens alone.”
Data Supporting the Approval
The accelerated approval was based on data from KEYNOTE-355 (ClinicalTrials.gov, NCT02819518), a multicenter, double-blind, randomized, placebo-controlled trial conducted in 847 patients with locally recurrent unresectable or metastatic TNBC, regardless of tumor PD-L1 expression, who had not been previously treated with chemotherapy in the metastatic setting. Patients were randomized (2:1) to receive either KEYTRUDA (200 mg on Day 1 every three weeks) or placebo (on Day 1 every three weeks) in combination with the following chemotherapy; all medications were administered via intravenous infusion:
Randomization was stratified by chemotherapy treatment (pac or nab-paclitaxel vs. gem and carbo), tumor PD-L1 expression (CPS ≥1 vs. CPS
