Survival outcomes with immune checkpoint inhibitor (ICI) treatment were improved among patients with non-small cell lung cancer (NSCLC) and SMARCA4 alterations compared with patients with STK11/KEAP1 comutations, according to results from a cohort study reported in a letter to the editor published in the Journal of Thoracic Oncology.

The letter was in reference to a study that reported poor outcomes among several patients with BRG1-deficient NSCLC with truncating SMARCA4 mutations who were treated with ICIs. “The results may have been influenced by the small sample size and comutations of STK11/KEAP1,” the authors wrote. The purpose of this analysis was to determine if there was an association between SMARCA4 mutations and outcomes with ICIs, without the confounding presence of STK11/KEAP1 mutations.

The study analyzed data from a publicly available cohort of 441 patients with NSCLC treated with ICIs at 2 different centers. SMARCA4 alterations included nonsense and frameshift mutations, insertions and deletions, and splice-site mutations that resulted in truncation. Baseline variables were similar between the SMARCA4-altered and wild-type groups.

In the cohort, 6.8% of patients (30) harbored a SMARCA4-truncating alteration, with 53% (16) patients also having STK11/KEAP1 comutations. Patients with SMARCA4 mutations had a median tumor mutational burden of 8.85 mut/Mb.  The majority of patients with SMARCA4 alterations received ICI monotherapy as first-line treatment (87%).

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Among the 296 patients with evaluable data, the objective response rate was higher in the SMARCA4-altered group at 53% compared with 20% in the wild-type group (P =.001).

Survival outcomes were prolonged in the SMARCA4-altered group with no STK11/KEAP1 comutations. Though not significant, there was a numerical improvement in overall survival, with a median not reached with SMARCA4 alterations alone compared with 5 months in the group with STK11/KEAP1 comutations (P =.06). Progression-free survival was significantly prolonged among patients with SMARCA4 alterations alone, with a median not reached compared with 1.8 months among patients with STK11/KEAP1 comutations (P =.01).

Efficacy outcomes were similar between the SMARCA4-altered and wild-type groups.

The authors concluded that “patients with pure SMARCA4 mutations were found to benefit more” from treatment with ICIs. They added that their findings could improve the management of patients with SMARCA4 mutations “according to the STK11/KEAP1 comutation status.”


Zhou H, Shen J, Liu J, Fang W, Zhang L. Efficacy of immune checkpoint inhibitors in SMARCA4-mutant NSCLC. J Thoracic Oncol. 2020;15:e133-e136. doi:10.1016/j.jtho.2020.03.030