The U.S. Food and Drug Administration approved the anti-PD-1 therapy as a monotherapy for patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 with disease progression after one or more previous lines of systemic therapy.
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Broadly, Merck’s checkpoint inhibitor Keytruda (pembrolizumab) has been approved for 21 indications. The U.S. Food and Drug Administration (FDA) approved the anti-PD-1 therapy as a monotherapy for patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 with 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,” stated Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories.
Cheng added, “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, providing an important new monotherapy option for physicians and patients in the United States.”
The FDA’s thumbs-up was based on data from KEYNOTE-181, a multicenter, randomized, open-label, active-controlled clinical trial with 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after a single previous line of systemic treatment. Patients who tested positive for HER2/neu esophageal cancer had to have received HER2/neu targeted therapy. All patients were tested for PD-L1 levels at a central laboratory using the PD-L1 IHC 22C3 pharmDx test kit.
Patients who had a history of non-infectious pneumonitis that required steroids, or who currently had pneumonitis, active autoimmune disease or any medical condition requiring immunosuppression treatment were ineligible.
The 628 patients were split randomly into even groups, one cohort receiving Keytruda 200 mg every three weeks or an investigator’s pick of several different chemotherapies, including paclitaxel, docetaxel, or irinotecan.
The major efficacy outcome measured was overall survival (OS) in several subpopulations. Additional efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR).
The approval also included data from KEYNOTE-180, a trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two previous systemic treatments.
Merck originally presented data on KEYNOTE-181 in January at the 2019 Gastrointestinal Cancer Symposium (ASCO GI). It was the first time an anti-PD-1 drug had shown a survival benefit in this patient population. There was a 31% decrease in the risk of death compared to a chemotherapy regimen of paclitaxel, docetaxel or irinotecan.
“The prognosis for patients diagnosed with esophageal cancer is poor, and for those who experience disease progression, there is no established standard of care, underscoring the need for improved therapies in the second-line setting,” stated Takashi Kojima, professor in the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, in January. “The significant improvement in overall survival observed with Keytruda in patients with squamous cell carcinoma or adenocarcinoma whose tumors expressed PD-L1 with a CPS of 10 or greater represents an important scientific advancement and has the potential to benefit patients who currently have limited treatment options.”
There are currently more than 1,000 clinical trials ongoing involving Keytruda in a variety of cancers and treatment settings. It is presently approved for a variety of indications in melanoma, non-small cell lung cancer, small cell lung cancer, head and neck cancer, classical Hodgkin Lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high (MSI-H) cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merckel Cell Carcinoma, and renal cell carcinoma.
