The US Food and Drug Administration has approved pembrolizumab (Keytruda) and pembrolizumab plus berahyaluronidase alfa-pmph (Keytruda QLEX), each in combination with sacituzumab govitecan-hziy (Trodelvy), for the first-line treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express programmed death ligand 1 with a Combined Positive Score of 10 or greater, according to a press release from Merck. The company said the approval is the first for a programmed death receptor-1 inhibitor combined with a Trop-2-directed antibody-drug conjugate in advanced triple-negative breast cancer.
The approval was based on the phase 3 KEYNOTE-D19/ASCENT-04 trial, which enrolled 443 patients with programmed death ligand 1 (PD-L1)-positive unresectable locally advanced or mTNBC who had not previously received systemic therapy for advanced disease. Patients were randomly assigned to receive pembrolizumab plus sacituzumab govitecan-hziy or pembrolizumab plus investigator's choice of chemotherapy, including paclitaxel, nab-paclitaxel, or gemcitabine with carboplatin. The primary endpoint was progression-free survival assessed by blinded independent central review.
According to Merck, pembrolizumab plus sacituzumab govitecan-hziy reduced the risk of disease progression or death by 35% compared with pembrolizumab plus chemotherapy. Median progression-free survival was 11.2 months compared with 7.8 months, respectively. The objective response rate was 61% in the pembrolizumab plus sacituzumab govitecan-hziy group and 55% in the pembrolizumab plus chemotherapy group. Complete responses occurred in 12% and 8% of patients, respectively. Merck said approval of pembrolizumab plus berahyaluronidase alfa-pmph was supported by data from pembrolizumab studies and the MK-3475A-D77 trial, which evaluated pharmacokinetic, efficacy, and safety outcomes.
“These approvals are heartening news for patients and the clinical community, and I believe offer practice-changing first-line treatment options," stated Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and a principal investigator of Merck’s KEYNOTE-D19 and Gilead’s ASCENT-04 study in the press release.
According to the press release, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend pembrolizumab plus sacituzumab govitecan-hziy as a category 1 preferred first-line treatment option for certain patients with recurrent unresectable or stage IV PD-L1-positive triple-negative breast cancer. Common adverse reactions included decreased neutrophil count, decreased hemoglobin, decreased leukocyte count, diarrhea, nausea, fatigue, alopecia, constipation, rash, and vomiting. Serious adverse reactions occurred in 38% of patients, and fatal adverse reactions occurred in 3.2% of patients.
Source: Merck