The US Food and Drug Administration has approved pembrolizumab (Keytruda, Merck), as well as its subcutaneous formulation pembrolizumab and berahyaluronidase (Keytruda Qlex, Merck), in combination with paclitaxel, with or without bevacizumab, for patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma that expresses PD-L1, after they’ve received one or two previous lines of systemic treatment.

The agency also approved the PD-L1 IHC 22C3 pharmDx test (Agilent Technologies) as a companion diagnostic to identify tumors with the required PD-L1 expression (combined positive score of 1 or higher).

The approval trial, KEYNOTE-B96, marked the first time that a checkpoint inhibitor-based regimen showed a survival benefit in platinum-resistant recurrent ovarian cancer, Merck said in a press release last October announcing the results. 

KEYNOTE-B96 randomly assigned 643 women equally to either pembrolizumab or placebo on a background of paclitaxel with or without bevacizumab. Patients must have received at least one line of platinum-based chemotherapy with radiographic evidence of progression within 6 months after the last dose.

Median progression-free survival was 8.3 months with pembrolizumab add-on vs 7.2 months with placebo (hazard ratio [HR], 0.72; P = .0014). Median overall survival was 18.2 months in the pembrolizumab arm vs 14 months (HR, 0.76; P = .0053). The benefit held regardless of the use of bevacizumab. 

Grade 3 or higher treatment-related adverse events occurred in 67.5% of patients in the pembrolizumab group and 55.3% in the placebo group, including three deaths in the pembrolizumab arm and five in the placebo group. 

Grade 3 or higher immune-mediated adverse events were reported in 11.6% of patients in the pembrolizumab arm and 3.5% of placebo patients; two of the three treatment-related deaths in the pembrolizumab arm were due to immune toxicities, pneumonitis, and colitis. The third death was due to intestinal perforation.

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks. The recommended dose of pembrolizumab and berahyaluronidase is 395 mg/4800 units every 3 weeks or 790 mg/9600 units every 6 weeks. Treatment continues until disease progression, unacceptable toxicity, or for up to 2 years.

Pembrolizumab should come before paclitaxel, with or without bevacizumab, if given the same day. 

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com