# KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer

Source: https://onco.cc/key-papers/paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020/  
OnCo record `paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-21
- Journal: Journal of Clinical Oncology
- Year: 2020
- DOI: 10.1200/JCO.19.02105
- Authors: Marabelle A, Le DT, Ascierto PA, et al.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- J Clin Oncol 2020: https://doi.org/10.1200/JCO.19.02105
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31682550/

## Connected records

- cancers: [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)](https://onco.cc/trials/nct02628067/)
- people: [Aurélien Marabelle](https://onco.cc/people/aurelien-marabelle/), [Dung T. Le](https://onco.cc/people/dung-le/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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