# Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of KEYNOTE-158

Source: https://onco.cc/key-papers/paper-marabelle-keynote-158-tmb-lancet-oncol-2020/  
OnCo record `paper-marabelle-keynote-158-tmb-lancet-oncol-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In ten hard-to-treat cancer types, 29 in 100 people whose tumours carried at least 10 mutations per million DNA letters responded to pembrolizumab, against 6 in 100 below that line.

## Summary

KEYNOTE-158 was a multi-cohort, open-label, non-randomised phase 2 study of pembrolizumab 200 mg every three weeks in previously treated advanced anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid and vulvar cancers, at 81 sites in 21 countries. Tissue tumour mutational burden was measured with FoundationOne CDx and the prespecified high cut-off was at least 10 mutations per megabase.

Of 1,050 patients enrolled at least 26 weeks before the June 2019 cut-off, 790 (75 per cent) were evaluable for TMB. 102 (13 per cent) were TMB-high and 688 were not. Objective responses occurred in 30 of 102 (29 per cent, 95 per cent confidence interval 21 to 39) of the high group and 43 of 688 (6 per cent, 5 to 8) of the rest. Grade 3 to 5 treatment-related adverse events occurred in 15 per cent of the high group. This analysis underpins the tumour-agnostic approval of pembrolizumab for TMB-high solid tumours.

## Fields

- Kind: Key paper
- Last checked: 2026-10-20
- Tags: precision
- Journal: The Lancet Oncology
- Year: 2020
- DOI: 10.1016/S1470-2045(20)30445-9
- Authors: Marabelle A, Fakih M, Lopez J, et al.
- Findings: 13 per cent of 790 evaluable patients had tissue TMB of at least 10 mutations per megabase on FoundationOne CDx.; Objective response 29 per cent in the TMB-high group against 6 per cent in the rest.; A quarter of treated patients had no evaluable TMB result.
- What it means: It is the evidence for one cut-off across many cancers. It was gathered in ten selected cancer types, and later analyses question whether the line sits in the same place for every tumour.
- Caveats: Non-randomised, so response in the TMB-high group is not compared with another treatment.; Ten selected cancer types; breast, prostate, colorectal and brain tumours were not among them.; One assay; panels measure TMB differently.

## Sources

- Marabelle et al., Lancet Oncol 2020: https://doi.org/10.1016/S1470-2045(20)30445-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32919526/

## Connected records

- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [Tumour mutational burden testing](https://onco.cc/technologies/tmb-testing/)
- drugs: [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- trials: [KEYNOTE-158](https://onco.cc/trials/keynote-158/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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