The FDA approved pembrolizumab as monotherapy for certain patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus.
The approval applies to use of pembrolizumab (Keytruda, Merck) for patients whose tumors express PD-L1 — with a combined positive score of 10 or higher — as determined by an FDA-approved test, and who experienced disease progression after one or more previous lines of systemic therapy.
“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” Jonathan Cheng, MD, vice president for oncology clinical research at Merck Research Laboratories, said in a company-issued press release. “With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment [for this patient population], providing an important new monotherapy option for physicians and patients in the United States.”
The FDA based the approval on results from the randomized controlled KEYNOTE-181 trial, which included 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced disease.
Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks or investigator’s choice of IV chemotherapy with paclitaxel, docetaxel or irinotecan. Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.
OS among three groups — patients with esophageal squamous cell carcinoma, those whose tumors express PD-L1 with a combined positive score of 10 or higher, and all randomly assigned patients — served as the key efficacy outcome.
Secondary outcomes included PFS, objective response rate and duration of response.
Researchers reported HRs for OS of 0.77 (95% CI, 0.63-0.96) among patients with esophageal squamous cell carcinoma; 0.7 (95% CI, 0.52-0.94) among patients whose tumors met the defined PD-L1 expression threshold; and 0.89 (95% CI, 0.75-1.05) among all randomly assigned patients.
Among patients with esophageal squamous cell carcinoma who met the defined PD-L1 expression threshold, those assigned pembrolizumab achieved longer median OS (10.3 months vs. 6.7 months; HR = 0.64; 95% CI, 0.46-0.9) and median PFS (3.2 months vs. 2.3 months; HR = 0.66; 95% CI, 0.48-0.92).
A higher percentage of pembrolizumab-treated patients achieved response (22% vs. 7%), complete response (5% vs. 1%) and partial response (18% vs. 6%). Median duration of response was 9.3 months in the pembrolizumab group and 7.7 months in the chemotherapy group.
Adverse reactions that occurred among pembrolizumab-treated patients with esophageal cancer appeared similar to those that have been observed among patients with melanoma or non-small cell lung cancer who received pembrolizumab monotherapy.
The FDA also considered data from the KEYNOTE-180 trial, a nonrandomized, open-label study that included 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease.
Thirty-five patients with esophageal squamous cell carcinoma expressed PD-L1 with a combined positive score of 10 or higher. Seven patients achieved response, equating to an ORR of 20%. The duration of response ranged from 4.2 months to more than 25.1 months. Five patients achieved responses that lasted 6 months or longer, and three patients achieved responses that lasted 12 months or longer.