Immune Checkpoint Inhibitors (Ici) Response In Metastatic Non-Small Cell Lung Cancer (Nsclc) Patients With Wnt Pathway Mutations (Apc/Ctnnb1).

e15137 Background: APC and CTNNB1 mutations (mut) lead to an aberrant activation of the WNT pathway which has been linked to lack of benefit of immunotherapy in patients (pts) with lung cancer. Our aim is to describe the pts’ characteristics of a NSCLC cohort with APC or CTNNB1 mut and their association with outcomes (Overall survival [OS] and Progression-Free-Survival [PFS]) when treated with ICI. Methods: We selected NSCLC pts with mut in APC or CTNNB1 by targeted NGS (tissue), whole exome sequencing (tissue) or Guardant 360(plasma) between January 2014 and October 2019. Functionality of mut and β-catenin protein expression by immunohistochemistry (IHC) were correlated with outcome. Results: We identified a total of 37 patients with 44 mutually-exclusive mutations in APC (31) or CTNNB1 (6), 25 adenocarcinomas (68%). Of APC mut cohort, 16 had pathogenic mut (52%) and 15 of unknown significance (48%). All 6 CTN NB1 mut were known pathogenic. Median OS (mOS) in metastatic setting was 21.6 months (m) (CI95% 14.9-NR), without differences between APC and CTNNB1 groups (HR 1.5, p = 0.4) or when stratified by mut functionality (HR 1.1, p = 0.8). Globally, 21 pts received treatment with ICI (57%, 19 APC, 2 CTNNB1), median PFS (mPFS) was 5.43m (1.8-21.7), with trend for shorter mPFS in CTNNB1 mut (mPFS 1.7m) vs. APC mut (mPFS 6.6m, HR 1.5, p = 0.1). Among patients treated with ICI, 8 (38%) had coexisting driver targetable alterations ( EGFR, ERBB2 or MET) and 13 (62%) other functional mut were found ( TP53, KRAS, STK11, BRCA2, ATM). mPFS was 3.9m (1.8-NR) in the subgroup with driver mut vs. 6.6m (1.4-NR) for remaining pts (HR 1.36, p = 0.5). In 15 pts β-catenin IHC was performed, being positive in 7 cases (47%), 4 of them received ICI with a mPFS 12.1m. Conclusions: In our experience, benefit with ICI is not influenced by the presence of APC mut, and small numbers of CTNNB1 cohort limit conclusive statements. Additional studies are required to assess WNT pathway activation on top of genomics and correlate with the ICI efficacy.