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FDA Approves Merck's Keytruda, Agilent CDx in PD-L1-High Triple-Negative Breast Cancer

NEW YORK – The US Food and Drug Administration on Friday granted accelerated approval to pembrolizumab (Merck's Keytruda) plus chemotherapy as a treatment for locally recurrent, unresectable, or metastatic triple-negative breast cancer patients with high PD-L1-expressing tumors.

Advanced TNBC patients must have a PD-L1 combined positive score of at least 10, as determined by an FDA-approved test, in order to receive the drug. On the same day, the agency also approved Agilent/Dako's PD-L1 IHC 22C3 pharmDx test as a companion diagnostic to identify those with PD-L1-high TNBC.

This is the first time pembrolizumab has been approved for treating breast cancer.

The agency approved this latest indication based on the Keynote-355 randomized study in which 847 chemotherapy-treated TNBC patients with recurrent, unresectable, or metastatic tumors received pembrolizumab and chemo or a placebo and chemo. In the subgroup of patients with a PD-L1 combined positive score of at least 10, median progression-free survival was 9.7 months in the pembrolizumab arm and 5.6 months in the placebo arm. The pembrolizumab-chemo combination improved PFS over just chemo in this subset of patients in the trial. 

Some common adverse events in pembrolizumab-treated patients were fatigue, nausea, diarrhea, and constipation, and 20 percent or more patients in the trial also had lab abnormalities indicative of anemia, leukopenia, and neutropenia.

For example, in 2019, the US Food and Drug Administration granted accelerated approval to atezolizumab (Genentech's Tecentriq) in combination with nab-paclitaxel for triple-negative breast cancer patients with PD-L1 positive tumors on the basis of a progression-free survival benefit. However, in a similarly designed study presented this fall, in which atezolizumab was combined with paclitaxel as opposed to nab-paclitaxel, the regimen failed to benefit the same patient population. Neither study used biomarkers other than PD-L1 to further home in on a best responder population.

The FDA last year granted accelerated approval to atezolizumab (Genentech's Tecentriq) in combination with paclitaxel protein-bound (Celgene's Abraxane) for PD-L1-expressing, metastatic TNBC. The agency also recently alerted healthcare professionals that atezolizumab plus paclitaxel, which is different than paclitaxel protein-bound, did not benefit TNBC patients enrolled in the Phase III IMpassion131 trial.