FDA Approves Pembrolizumab for Platinum-Resistant Ovarian Cancer
The FDA approved pembrolizumab in combination with paclitaxel, with or without bevacizumab, for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1).
On February 10, the U.S. Food and Drug Administration approved the PD-1 inhibitor pembrolizumab (Keytruda) as well as pembrolizumab and the recombinant human enzyme, berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with paclitaxel, with or without bevacizumab. The indication is for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (combined positive score ≥ 1) as determined by an FDA-authorized test, and who have received one or two prior systemic treatment regimens. Pembrolizumab plus berahyaluronidase alfa is administered by subcutaneous injection.
Efficacy was evaluated in KEYNOTE-B96 (ClinicalTrials.gov identifier NCT05116189), a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 643 patients with platinum-resistant, epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who received one or two prior lines of systemic therapy. Patients were randomly assigned 1:1 to receive either pembrolizumab plus paclitaxel with or without bevacizumab or placebo plus paclitaxel with or without bevacizumab.
The major efficacy outcome measure was progression-free survival; an additional efficacy outcome measure was overall survival. Among the 466 patients with tumors expressing PD-L1 with CPS ≥ 1, median progression-free survival was 8.3 months (95% confidence interval = 7.0–9.4 months) in the pembrolizumab arm and 7.2 months (95% CI = 6.2–8.1 months) in the placebo arm (hazard ratio = 0.72, 95% CI = 0.58–0.89, P = .0014). Median overall survival was 18.2 months (95% CI = 15.3–21.0 months) in the pembrolizumab arm and 14.0 months (95% CI = 12.5–16.1 months) in the placebo arm (HR = 0.76, 95% CI = 0.61–0.94, P = .0053).
The overall safety profile of pembrolizumab in combination with paclitaxel with or without bevacizumab in KEYNOTE-B96 was similar to that observed in prior trials. The most common adverse reactions reported with pembrolizumab in combination with paclitaxel with or without bevacizumab were diarrhea, fatigue, nausea, alopecia, peripheral neuropathy, epistaxis, urinary tract infection, constipation, abdominal pain, decreased appetite, vomiting, hypothyroidism, cough, hypertension, and rash. Laboratory abnormalities included anemia, leukopenia, decreased neutrophil count, lymphopenia, hypoalbuminemia, hyponatremia, hypomagnesemia, increased aspartate aminotransferase, increased alanine aminotransferase, hypocalcemia, increased alkaline phosphatase, increased creatinine, hypokalemia, and neutropenia.
The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose of pembrolizumab and berahyaluronidase alfa is 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.
The FDA also approved the immunohistochemical assay PD-L1 IHC 22C3 pharmDx as a companion diagnostic device to identify patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS≥1) for treatment with pembrolizumab.