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The routine gene panel used in clinic can estimate how many mutations a lung cancer carries almost as well as sequencing the whole exome can, and tumours with more mutations were more likely to benefit from immunotherapy, independently of the PD-L1 stain.
Detailed clinical annotation and response data were collected for 240 patients with advanced non-small-cell lung cancer treated with anti-PD-1 or anti-PD-L1 therapy and profiled with a targeted next-generation sequencing panel. Durable clinical benefit was defined as partial response or stable disease lasting more than six months. Panel-based tumour mutation burden correlated well with whole-exome estimates in 49 patients (rho 0.86). Burden was greater in patients with durable benefit than in those without (p = 0.006). Durable benefit was more common and progression-free survival longer above the 50th percentile of burden (38.6% against 25.1%; hazard ratio 1.38). The fraction of copy number-altered genome was highest in patients without durable benefit. Variants in EGFR and STK11 were associated with a lack of benefit. Burden and PD-L1 expression were independent, and a composite of the two enriched further for benefit.
It made tumour mutational burden measurable in routine practice and, in the same stroke, showed it is a second axis alongside PD-L1 rather than a replacement for it.
Shares Matthew D. Hellmann, Tumour mutational burden testing, PD-L1 TPS (tumour proportion score), TMB-high (tumour mutational burden >= 10 mutations per megabase).
Shares STK11 / KEAP1 co-mutations, Tumour mutational burden testing, PD-L1 TPS (tumour proportion score), STK11.
Shares STK11 / KEAP1 co-mutations, Tumour mutational burden testing, STK11, TMB-high (tumour mutational burden >= 10 mutations per megabase).
Shares Tumour mutational burden testing, TMB-high (tumour mutational burden >= 10 mutations per megabase), Neoantigen, The cancer-immunity cycle.
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), Tumour mutational burden (TMB), PD-1 / PD-L1 immune checkpoint & T-cell activation.
Shares STK11 / KEAP1 co-mutations, STK11, PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Tumour mutational burden (TMB), PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1.