Updated results from the KEYNOTE 059 phase II trial showed that pembrolizumab alone or in combination with chemotherapy has promising antitumor activity for patients with advanced gastric or gastroesophageal junction cancer.
Lead author Zev Wainberg, MD, co-director of the Gastrointestinal Oncology Program at University of California Los Angeles, presented results (abstract LBA28_PR) at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid.
The study included three patient cohorts: cohort 1 assigned 259 patients with two or more prior lines of therapy to pembrolizumab alone; cohort 2 assigned 25 patients to first-line pembrolizumab and cisplatin plus 5-fluorouracil or capecitabine; cohort 3 assigned 31 patients with PD-L1 positive tumors to first-line pembrolizumab alone. The primary endpoint was safety in all cohorts and overall response rate in cohorts 1 and 3.
The median follow-up for cohort 1 was 6 months. In cohort 1, the overall response rate was 12%. The response was 16% in patients with PD-L1–positive tumors and 6% in PD-L1–negative tumors. Grade 3 to 5 treatment-related adverse events occurred in almost one in five (18%) patients in cohort 1, and 3% of patients had to discontinue treatment as a result.
“The data shows that the tumors were sufficiently shrunk to warrant a response, particularly in those patients who had PD-L1 expression, and the drug was safe,” Wainberg said in a press release. “The expected response rate in these heavily pretreated patients was close to zero so the findings are encouraging.”
Patients treated with pembrolizumab as a first-line therapy also had promising results. Patients in cohort 2 had a median follow-up of 14 months. In cohort 2 the overall response rate was 60%. Similar to cohort 1, patients with PD-L1–positive tumors had a higher response rate than those with PD-L1–negative tumors (73% vs 38%). The median follow-up in cohort 3 was 18 months. In this cohort, which had only PD-L1–positive tumors, the overall response rate was 26%.
The median progression-free survival was 2 months, 7 months, and 3 months, for cohorts 1, 2, and 3, respectively.
Commenting on the results for ESMO, Ian Chau, MD, consultant medical oncologist, Royal Marsden Hospital, London and Surrey, United Kingdom, said: “There is currently no standard of care for metastatic gastric cancer treated in the third line or beyond. The KEYNOTE-059 cohort 1 results confirm that the efficacy previously reported for the PD-1–inhibitor nivolumab in patients from East Asia in the ONO-4538 randomized trial can be applied to Western populations.”
“The likelihood is that pembrolizumab will become a standard treatment option in this setting in the near future,” he added.
However, Chau cautioned that while the toxicity profile of pembrolizumab looked quite favorable in KEYNOTE-059, it could be that patients had not been treated long enough to experience side effects. He said: “Unlike with chemotherapy, toxicities from immunotherapy tend to occur later on. We need to await longer-term results from an ongoing clinical trial in an earlier line of treatment to know the full impact of this drug in metastatic gastric cancer.”