FDA approved yet another indication for pembrolizumab (Keytruda, Merck) to treat patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC).
The indication is specifically for patients with ESCC whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), as determined by companion test PD-L1 IHC 22C3 pharmDx kit, with disease progression after one or more prior lines of systemic therapy.
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Keytruda is already indicated to treat refractory classical Hodgkin lymphoma (cHL), urothelial carcinoma, gastric cancer, esophageal cancer, cervical cancer, renal cell carcinoma (RCC), and several other cancers.
“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories, in a Merck statement. “With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment of previously-treated patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10), providing an important new monotherapy option for physicians and patients in the US.”
The recommended Keytruda dose for esophageal cancer is 200 mg every 3 weeks.
Efficacy was investigated in 2 clinical trials, KEYNOTE‑181 (NCT02564263) and KEYNOTE‑180 (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.
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The primary efficacy outcome measure of KEYNOTE-181 was overall survival (OS) in patients with ESCC, patients with tumors expressing PD-L1 CPS ≥10, and all randomized patients. Additional efficacy outcome measures were progression-free survival (PFS), overall response rate (ORR), and response duration. The hazard ratio for OS in patients with ESCC whose tumors expressed PD-L1 CPS ≥10 was 0.64. Median OS 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 2 prior systemic treatments for advanced disease. The major efficacy outcome measures of KEYNOTE-180 were ORR and response duration.
In the 35 patients with ESCC expressing PD-L1 CPS ≥10, ORR was 20% and response durations ranged from 4.2 to 25.1+ months, with 71% having responses of 6 months or longer and 57% having responses of 12 months or longer, according to FDA.
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