The US Food and Drug Administration (FDA) today approved pembrolizumab (Keytruda, Merck) for treatment of gastric or gastroesophageal junction cancer. Pembrolizumab becomes the first immunotherapy approved in the United States for gastric cancer.
The approval is limited to patients who have had at least two previous lines of chemotherapy for these recurrent locally advanced or metastatic adenocarcinomas that express programmed death receptor-ligand 1 (PD-L1). The PD-L1 expression must be determined by an FDA-approved test and have a combined positive score (CPS) ≥1.
Pembrolizumab is also now the first third-line therapy to be approved in this setting.
The new indication is approved under the FDA's accelerated approval regulations based on tumor response rate and duration of response.
More specifically, the approval is based on results from the open-label, nonrandomized KEYNOTE-059 study, which were presented at the American Society of Clinical Oncology annual meeting in June.
In the multinational trial, 259 heavily pretreated patients received single-agent pembrolizumab at a flat 200-mg dose every 3 weeks. Before enrolling, 51.7% of patients had received 2 prior lines of therapy, and 29% and 19.3% had received 3 or ≥ 4 prior lines of therapy, respectively. Median follow-up was 5.8 months.
In the study, 143 of 259 patients had PD–L1-positive tumors (CPS ≥ 1) and microsatellite stable tumor status or undetermined microsatellite instability or mismatch repair status. The objective response rate (ORR) in these patients was 13.3%, comprising 1.4% complete responses and 11.9% partial responses.
Among the 19 patients who were responders, the duration of response ranged from 2.8+ to 19.4+ months, with 58% having responses 6 months or longer and 26% having responses 12 months or longer.
"That's a relatively unprecedented duration of response in third-line gastric cancer," Charles Fuchs, MD, MPH, told Medscape Medical News this week, speaking about the 6- and 12-month responses. Dr Fuchs is director of the Yale Cancer Center in New Haven, Connecticut, and the global principal investigator of the KEYNOTE-059 trial.
The median duration of response in the first-line treatment of gastric cancer with standard cytotoxic chemotherapy is "a few months," said Dr Fuchs.
"There is no approved agent for the third-line treatment of gastric cancer, so in principle, these patients had no FDA approved treatment option," he added.
There is another outstanding take-away regarding use of pembrolizumab in gastric cancer, said Dr Fuchs: "The earlier the line of therapy, the higher the rate of response."
Among patients who received only 2 prior lines of therapy, the ORR was 16.4%, which was higher than the 11.6% rate for all of the trial's patients.
Pembrolizumab is well tolerated. The most frequently occurring treatment-related adverse events of all grades were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, and constipation. There were two treatment-related deaths.
Pembrolizumab is not the only immunotherapy evaluated in gastric cancer.
Dr Fuchs acknowledged that nivolumab has "compelling data" in ongoing studies that show "similar responses."
"At some point, I suspect that it [nivolumab] too will be available and FDA approved," he said.
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Cite this: First Immunotherapy Approved for Gastric Cancer - Medscape - Sep 22, 2017.