Abstract 783: Impact of KRAS and TP53 co-mutations on outcomes following 1st-line therapy among patients with LKB1/STK11 mutated stage IV NSCLC
Authors: Bange Erin M. , Marmarelis Melina E. , Hwang Wei-Ting , Yang Yu-Xiao , Thompson Jeffrey C. , Bauml Joshua , Ciunci Christine A. , Alley Evan W. , Evans Tracey L. , Morrissette Jennifer J. , Cohen Roger B. , Langer Corey J. , Carpenter Erica L. , Aggarwal Charu 
Published: August 2018

* Authors E. M. B. and M. E. M. contributed equally

Introduction: LKB1/STK11 is a tumor suppressor and a negative regulator of mTOR signaling. NSCLC patients with STK11 mutations (MT) commonly also have other co-mutations. We evaluated the impact of STK11 MT on outcomes following chemotherapy for metastatic NSCLC, and the role of common co-existing MTs in KRAS and TP53.

Methods: We conducted a retrospective review of patients (pts) with NSCLC and STK11 MT treated at the University of Pennsylvania. STK11 MT was identified through next generation sequencing (NGS) in tissue or using the Guardant 360TM platform for plasma. Four treatment groups were analyzed: STK11 alone (A), and 3 co-MT groups: STK11/KRAS (B), STK11/TP53 (C), and STK11/KRAS/TP53 (D). Chi-square analysis was used to assess differences in baseline characteristics between the MT groups. Cox proportional hazard models (HR) were used to determine the relationship of STK11 co-MT to survival. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression-free survival (PFS).

Results: Between 2/14/13 and 12/1/16, 77 pts with STK11 MT who received systemic therapy were identified (56 tissue, 21 plasma): median age at diagnosis 66 yrs, 51.5% male, 85% ECOG PS of 0 or 1, 94% of pts received 1st-line chemotherapy. There were no significant differences in baseline characteristics among mutation groups. Pts with STK11/KRAS had a worse median PFS and OS vs. pts with STK11 alone (Table 1). Pts with STK11/TP53 had a significantly better OS compared to STK11/KRAS patients.

Conclusion: Among STK11 mutant NSCLC pts treated with chemotherapy, co-MT with KRAS was associated with a significantly worse PFS and OS compared to patients with STK11 alone. By contrast, co-MT with TP53 conferred a better prognosis. These results warrant further validation in a larger study.

Table 1: Outcomes by mutation statusA:STK11alone n=16 (24.2%)B:STK11/KRAS n=21 (31.8%)C:STK11/TP53 n=18 (27.3%)D:STK11/KRAS/TP53 n=11 (16.7%)Median PFS5.3 mo2.4 mo*9.9mo4.9 moMedian OS13.1 mo6.9 mo**22.2 mo***13.9 mo*compared to A, HR 2.8, 95% CI 1.1 to 6.9, p = 0.026**compared to A, HR 6.4, 95% CI 2.4 to 17.3, p&lt;0.001***compared to B, HR 0.12, 95% CI 0.04 to 0.31, p&lt;0.001

Citation Format: Erin M. Bange, Melina E. Marmarelis, Wei-Ting Hwang, Yu-Xiao Yang, Jeffrey C. Thompson, Joshua Bauml, Christine A. Ciunci, Evan W. Alley, Tracey L. Evans, Jennifer J. Morrissette, Roger B. Cohen, Corey J. Langer, Erica L. Carpenter, Charu Aggarwal. Impact of KRAS and TP53 co-mutations on outcomes following 1st-line therapy among patients with LKB1/STK11 mutated stage IV NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 783.