Anti–PD-1 Immunotherapy in Previously Treated Gastric Cancer


Key Points

  • The objective response rate was 11.6%, with median response duration of 8.4 months.
  • In PD-L1–positive patients, the response rate was 15.5%, with median response duration of 16.3 months.

As reported in JAMA Oncology by Fuchs et al, pembrolizumab (Keytruda) showed activity in patients with previously treated advanced gastric and gastroesophageal junction cancer in the phase II KEYNOTE-059 trial.

Study Details

In the study, 259 patients from sites in 16 countries who had disease progression after two or more prior chemotherapy regimens that included a fluoropyrimidine and a platinum doublet as adjuvant treatment or for metastatic disease were enrolled between March 2015 and May 2016 and treated with pembrolizumab 200 mg every 3 weeks until disease progression, patient withdrawal, or unacceptable toxicity.  Tumors were considered programmed cell death ligand 1 (PD-L1)–positive if the combined expression score for tumor cells, macrophages, and lymphocytes was ≥ 1%. Overall, 148 patients (57.1%) were PD-L1–positive.

The primary endpoint was objective response on central review using RECISTv1.1 criteria.

Response Rates

Median follow-up was 5.8 months (range = 0.5–21.6 months). Objective response was observed in 30 patients (11.6%), with complete response in 6 (2.3%). Median duration of response was 8.4 months (range =1.6+–17.3+ months). Response rates were 15.5% and 6.4% in patients with PD-L1–positive and PD-L1–negative disease, with median response durations of 16.3 months (range = 1.6+ to 17.3+ months) and 6.9 months (range = 2.4 to 7.0+ months). 

Adverse Events

Grade ≥ 3 treatment-related adverse events occurred in 46 patients (17.8%), with the most common being anemia (2.7%) and fatigue (2.3%). Treatment-related adverse events led to treatment discontinuation in 2 patients (0.8%). Immune-related adverse events of any grade occurred in 46 patients (17.8%, grade 3 or 4 in 4.6%), with the most common being hypothyroidism (8.9%), hyperthyroidism (3.5%), and colitis (2.3%). Two patients (0.8%) died from adverse events considered related to treatment (acute kidney injury and pleural effusion).

The investigators concluded, “Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted.”

The study was supported by Merck & Co.

Charles S. Fuchs, MD, MPH, of Yale Cancer Center, Yale School of Medicine, is the corresponding author for the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.