STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world

Background Mutations inSTK11(STK11m) and frequently co-occurringKRASmutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. Methods This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence ofSTK11m andKRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). Results Of 2407 patients with mNSCLC,STK11m andKRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients withSTK11m versusSTK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends.KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versusKRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vsSTK11wt) findings. Conclusions This large observational genomic study among patients receiving routine care highlights the negative prognostic impact ofSTK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.