CONTRADICTING EVIDENCE: In terms of prognostic effect with ICIs therapy, TGFBR2mut were significantly associated with the overall survival (OS) of NSCLC (median, 2 months vs 11 months; HR = 3.46; 95% CI, 1.63-7.35; P ＜0.001) in OAK and POPLAR cohort, same as MSKCC cohort (median, 3 months vs 10 months; HR = 2.21; 95% CI, 1.04-4.71; P = 0.034). Interestingly, In the MSKCC cohort, opposite with NSCLC, majority tumors with TGFBR2mut had a longer survival value, showing a trend toward longer survival....The TGFBR2 might a potential biomarker for ICIs therapy in NSCLC, and the immune microenvironment may be a factor affecting of it.

In the discovery cohort, patients with TGFBR2 mutations had shorter progression-free survival (PFS, median, 1.3 months vs 2.7 months; HR = 2.83; 95% CI, 1.33–6; p = 0.0046) and dramatically shorter overall survival (OS, median, 2.4 months vs 11.1 months; HR = 3.46; 95% CI, 1.63–7.35; p = 0.00058) than those with wild-type TGFBR2....TGFBR2 gene mutations are associated with shorter survival in NSCLC patients treated with ICIs...

In the POPLAR/OAK cohort, patients with mutated TGFBR2 had shorter progression-free survival (P = 0.004; HR, 2.83; 95% CI, 1.34-6.00) and overall survival (OS) (P = 0.0006; HR, 3.46; 95% CI, 1.63-7.35) than patients with wild-type TGFBR2 when treated with ICIs....TGFBR2 mutation as a negative predictor for ICIs in NSCLC and the clinical use of ICIs needs to be cautious in those patients, highlighting the importance of genomic profiling in the treatment of ICIs.