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WASHINGTON -- The FDA on Friday to pembrolizumab (Keytruda) for treating triple-negative breast cancer (TNBC) patients with metastatic or locally recurrent unresectable disease.

TNBC becomes the astonishing 18th , which was first approved in 2014 for advanced or unresectable melanoma.

Pembrolizumab, a PD-1-directed immune checkpoint blocker, is approved in combination with chemotherapy and indicated for TNBC patients with a PD-L1 combined positive score (CPS) ≥10.

Approval was based on findings from KEYNOTE-355, a multicenter phase III trial that randomized 847 patients with metastatic or locally recurrent unresectable TNBC to chemotherapy plus either placebo or pembrolizumab. About 38% of patients had PD-L1 expression levels reaching CPS ≥10.

Median progression-free survival among the CPS ≥10 subgroup improved from 5.6 months in the placebo arm to 9.7 months with the addition of pembrolizumab (HR 0.65, 95% CI 0.49-0.86, one-sided P=0.0012). Data on overall survival were still immature.

"Approximately 15%-20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer," Hope Rugo, MD, of the University of California San Francisco, said in a from drugmaker Merck.

"Notably, in KEYNOTE-355, Keytruda was combined with three different chemotherapy regimens: paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin," said Rugo. "The approval of Keytruda in combination with chemotherapy gives physicians an important new option for appropriate patients."

The overall response rate (ORR) in the pembrolizumab arm was 53%, including complete responses in 17%, as compared to an ORR of 40% in the control arm, with complete responses in 13%. Median duration of response was 19.3 months versus 7.3 months, respectively.

In the trial, pembrolizumab was delivered intravenously at a dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, but the agent is also approved for TNBC at a dose of 400 mg every 6 weeks.

As a condition of the accelerated approval, further description of the drug's clinical benefit in this setting or confirmatory trials may be required, FDA noted.

Common adverse events (≥20%) of any grade with pembrolizumab plus chemotherapy in KEYNOTE-355 included alopecia, constipation, cough, decreased appetite, diarrhea, fatigue, headache, nausea and vomiting, and rash. Laboratory abnormalities (≥20%) in the pembrolizumab arm included anemia, elevated liver enzymes, hyperglycemia, hypoalbuminemia, hypocalcemia, hyponatremia, hypophosphatemia, hypokalemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia, and increased alkaline phosphatase.

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