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In a large randomised trial of immunotherapy given alone, patients whose tumours carried more mutations did better on the drug than on chemotherapy, and patients with fewer mutations did not.
This retrospective exploratory analysis of the phase 3 KEYNOTE-042 trial assessed tissue tumour mutational burden and STK11, KEAP1 and KRAS mutations, determined by whole-exome sequencing of tumour and matched normal DNA, in patients with PD-L1-positive advanced non-small-cell lung cancer without EGFR or ALK alterations. Of 793 patients, 345, 43.5%, had a burden of 175 or more mutations per exome. No association was observed between PD-L1 expression and burden. Continuous burden was associated with improved overall and progression-free survival among patients receiving pembrolizumab but not chemotherapy. A burden of 175 or more favoured pembrolizumab over chemotherapy (overall survival hazard ratio 0.62) where a burden below 175 did not (1.09). Improved overall survival with pembrolizumab was seen regardless of STK11, KEAP1 or KRAS mutation status.
It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, Tumour mutational burden testing, KEAP1.
Shares STK11 / KEAP1 co-mutations, Tumour mutational burden testing, PD-L1 TPS (tumour proportion score), STK11.
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Tumour mutational burden testing, PD-L1 TPS (tumour proportion score), TMB-high (tumour mutational burden >= 10 mutations per megabase), The cancer-immunity cycle.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1, STK11.
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), Tumour mutational burden (TMB), PD-1 / PD-L1 immune checkpoint & T-cell activation.