KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer
Pembrolizumab shrank tumours in about a third of patients with mismatch repair-deficient cancers of many different organs, with responses that often lasted years; the pancreatic cancer group responded less often than most. It is the trial behind the tissue-agnostic approval for MSI-high cancer.
Overview
Phase 2 basket study of pembrolizumab 200 mg every three weeks in 233 patients with previously treated advanced non-colorectal MSI-high or mismatch repair-deficient cancer across 27 tumour types, endometrial, gastric, cholangiocarcinoma and pancreatic cancer among the largest cohorts.
The objective response rate was about 34 percent with a median duration of response not reached, median progression-free survival 4.1 months and median overall survival 23.5 months. In the 22 patients with pancreatic cancer the response rate was about 18 percent and median overall survival about 4 months, the lowest of the major cohorts. The data supported the FDA's tissue-agnostic approval of pembrolizumab for MSI-high cancer.
- Objective response about 34 percent across 27 non-colorectal tumour types; median overall survival 23.5 months.
- Pancreatic cohort of 22 patients: response about 18 percent, median overall survival about 4 months.
Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.
- Single-arm basket study; the pancreatic cohort was small and heavily pretreated.
- Some patients had MSI-high status assigned by PCR or immunohistochemistry alone, and misclassification is a known problem in pancreatic cancer.
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