Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation

Background: STK11 mutation (STK11m) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown. Methods: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival. Results: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11m. 5/16 with STK11m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were not statistically different (STK11m vs. STK11w): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 >= 50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49). Conclusions: In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w. Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.