Keytruda Receives Broader Indication for Stomach Cancer

New indication targets advanced cases with PD-L1 expression

Pembrolizumab (Keytruda, Merck) has received a new FDA approval for the treatment of certain patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

 The new indication covers patients whose tumors express programmed death ligand-1 (PD-L1) with a combined positive score of at least one as determined by an FDA-approved test. Under the approval, these patients should exhibit disease progression on or after two or more prior lines of therapy, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.

This indication received accelerated approval based on tumor response rate and durability of response.

 “Historically, advanced gastric cancer has been particularly challenging to treat, and new treatment options are needed for these patients,” said Charles S. Fuchs, MD, MPH, lead investigator and director of Yale Cancer Center. “The results observed in the diverse population of heavily pretreated advanced gastric or GEJ patients from the KEYNOTE-059 clinical trial demonstrate that pembrolizumab in the third-line setting has the potential to shift how we care for certain patients facing this difficult-to-treat disease.”

Immune-mediated adverse reactions occurred with pembrolizumab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered if appropriate. Pembrolizumab can also cause severe or life-threatening infusion-related reactions.

Pembrolizumab became the first PD-1 checkpoint inhibitor approved in the United States for previously treated advanced gastric or GEJ cancer, helping to address a recognized treatment gap, Merck said.

The multicenter, nonrandomized, open-label multicohort KEYNOTE-059 trial enrolled 259 patients with gastric or GEJ adenocarcinoma who progressed on at least two prior systemic treatments for advanced disease. Previous treatment must have included a fluoropyrimidine and platinum doublet; HER2/neu-positive patients must have previously received treatment with approved HER2/neu-targeted therapy. Patients with active autoimmune disease or a medical condition that required immunosuppression or with clinical evidence of ascites by physical exam were ineligible.

Patients received pembrolizumab at a dose of 200 mg every three weeks until unacceptable toxicity or disease progression that was symptomatic, rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at least four weeks later with repeat imaging. Patients without disease progression were treated for up to 24 months. Assessment of tumor status was performed every six to nine weeks. The major efficacy outcome measures were objective response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by independent central review, and duration of response.

Among the 259 patients, 55% (n = 143) had tumors that expressed PD-L1 with a combined positive score of at least one and microsatellite stable (MSS) tumor status or undetermined microsatellite instability (MSI) or mismatch repair (MMR) status.

For the 143 patients, the ORR was 13.3%, with a complete response rate of 1.4% and a partial response rate of 11.%. Among the 19 responding patients, the duration of response ranged from 2.8-plus to 19.4-plus months, with 11 patients (58%) having responses of six months or longer and five patients (26%) having responses of 12 months or longer.

Among the 259 patients, seven (3%) had tumors that were determined to be MSI-High. An objective response was observed in four patients, including one complete response. The duration of response ranged from 5.3-plus to 14.1-plus months.

Source: Merck; September 22, 2017.