FDA Approves Pembrolizumab in PD-L1–Expressing Squamous Cell Carcinoma of the Esophagus
Posted: Thursday, August 1, 2019
On July 30, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. The FDA also approved a new use for the PD-L1 IHC 22C3 pharmDx kit as a companion diagnostic device for selecting patients for this indication of pembrolizumab.
Efficacy was investigated in two clinical trials, KEYNOTE-181 (CliniclTrials.gov identifier NCT02564263) and KEYNOTE-180 (CliniclTrials.gov identifier NCT02559687). KEYNOTE-181 was a randomized, open-label, active-controlled trial that enrolled 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced or metastatic disease. The primary efficacy outcome measure of KEYNOTE-181 was overall survival in patients with , squamous cell carcinoma of the esophagus, patients with tumors expressing PD-L1 Combined Positive Score ≥ 10, and all randomized patients. Median overall survival was 10.3 months and 6.7 months in the pembrolizumab and control arms, respectively.
KEYNOTE-180 was a single arm, open-label trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease. With the exception of the number of prior lines of treatment, the eligibility criteria were similar to and the dosage regimen identical to KEYNOTE-181.
In the 35 patients with squamous cell carcinoma of the esophagus expressing PD-L1 Combined Positive Score ≥ 10, overall response rate was 20% and response durations ranged from 4.2 to 25.1+ months, with 71% (n = 5) having responses of 6 months or longer and 57% (n = 3) having responses of 12 months or longer.
Adverse reactions in patients with esophageal cancer were similar to those in 2,799 patients with melanoma or non–small cell lung cancer treated with single-agent pembrolizumab. Common adverse reactions reported in at least 20% of patients receiving pembrolizumab include fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.
The recommended pembrolizumab dose for esophageal cancer is 200 mg every 3 weeks.