An immunotherapy drug receives FDA approval for stomach cancer treatment for the first time

On September 22, 2017, the American Food and Drug Administration FDA, for patients whose tumors are positive for PD-L1 and who have recurrent locally advanced or metastatic, gastric or gastroesophageal junction cancer, granted accelerated approval to the cancer immunotherapy pembrolizumab (brand name Keytruda). For the first time, stomach cancer received FDA approval for an immunotherapy drug.

Most cancers occurring in the stomach (gastric) and at the stomach–esophagus (gastroesophageal) junction are of the adenocarcinoma cell type. Cancer begins in the cells forming the mucosa, the innermost layer. Other, less common subtypes of stomach cancer (such as gastrointestinal stromal tumors, lymphoma and carcinoid tumors) are always referred to by their own names; unless otherwise specified, stomach cancer means gastric adenocarcinoma.

For immunotherapy to be used in these patients with gastric or gastroesophageal junction adenocarcinoma, prior fluoropyrimidine- and platinum-containing chemotherapy and, where appropriate, HER2-targeted therapy were included in the requirement to have received two or more previous systemic treatments.

Unlike conventional chemotherapy, cancer immunotherapies do not directly kill cancer cells; they trigger, strengthen and reorganize the immune system to fight cancer.

Approval is based on the results of an open-label, multicenter, noncomparative, multicohort study involving 259 patients with gastric or gastroesophageal junction adenocarcinoma, KEYNOTE 059. Of the 259 patients, % 55 had tumors positive for PD-L1 or microsatellite stable (MSS), or had undetermined microsatellite instability (MSI) or mismatch repair (MMR) status.

For PD-L1-positive patients, the group of 143 patients with MSS or undetectable MSI or dMMR had an objective response rate of % 13.3. Patients had a complete response in % 1.4 of cases and a partial response in % 11.9. Among the 19 responding patients, response duration ranged from 2.8 to 19.4 months, with 11 patients (% 58) having responses lasting 6 months or longer and 5 patients (% 26) having responses lasting 12 months or longer.

Among patients enrolled in KEYNOTE 059, out of 259 patients, 7 (% 3) had tumors identified as MSI-high. Of these 7 patients, 4 responded (one complete response). Response duration ranged from 5.3 to 14.1 months.

The interaction of PD-1 with PD-L1 is blocked by pembrolizumab, a cancer immunotherapy in the anti-PD-1 class . Side effects observed in stomach cancer patients receiving it were similar to the previously described immunotherapy side effects . The most common were fatigue, musculoskeletal pain, decreased appetite, rash, diarrhea, nausea, flushing, fever, cough, shortness of breath (dyspnea) and constipation.

The recommended pembrolizumab dose for stomach cancer is an intravenous infusion (through a vein with an IV solution) every 3 weeks over 30 minutes, at 200 mg, until disease progression or unacceptable side effects develop. It is administered for up to 24 months in patients whose cancer does not progress.

On the same day as this approval, the FDA also approved the test named PD-L1 IHC 22C3 pharmDx to select stomach cancer patients eligible for pembrolizumab treatment. If an old tissue sample tested for PD-L1 does not yield a positive result, the FDA recommended obtaining a new tumor biopsy if possible.