June 13, 2018—Yesterday, the U.S. Food and Drug Administration (FDA) granted accelerated approval of the PD-1 checkpoint inhibitor pembrolizumab for patients with recurrent or metastatic PD-L1–positive cervical cancer who’s disease progressed on or after chemotherapy. For this approval, PD-L1 positivity is defined as a combined positive score (CPS) of ≥1 as measured by an FDA-approved test.

Yesterday’s approval was based on results from the single cohort phase II KEYNOTE-158 study (NCT02628067) in which 98 patients with recurrent or metastatic cervical cancer were treated with pembrolizumab intravenously at a dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity. Of the 98 patients enrolled in this trial, 77 (79%) had PD-L1–positive disease as determined using the aforementioned test.
 
With a median follow-up time of 11.7 months, the objective response rate (ORR) in the 77 PD-L1–positive patients was 14.3%, including a complete response rate of 2.6% and a partial response rate of 11.7%. The median duration of response had not yet been reached (range 4.1, 18.6+ months). Overall, 91% of patients who responded had a response duration of at least 6 months. Further, no responses were observed in patients whose tumors did not express PD-L1.
 
In the KEYNOTE-158 study, pembrolizumab was discontinued due to adverse events (AEs) in 8% of patients. Serious AEs occurred in 39% of enrolled patients and included anemia (7%), fistula (4.1%), hemorrhage (4.1%), and infections (4.1%). Other common AEs included fatigue, pain, pyrexia, peripheral edema, musculoskeletal pain, diarrhea/colitis, abdominal pain, nausea, vomiting, constipation, decreased appetite, hemorrhage, UTI, other infections, rash, hypothyroidism, headache, and dyspnea.
 
The accelerated approval for pembrolizumab in this setting is contingent on the results of a confirmatory trial. Along with yesterday’s new indication, pembrolizumab has also been approved in melanoma, lung cancer, head and neck cancer, lymphoma, urothelial carcinoma, gastric cancer, and solid tumors with microsatellite instability–high (MSI-H) phenotype.
 
Updated prescribing information for pembrolizumab can be found here.
 
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Jonathan A. Bell
Published Online: Wednesday, June 13, 2018