Co-mutational status and PD-L1 expression in KRAS mutant non-small cell lung cancer (NSCLC): Role in treatment selection and association with clinical outcomes.
Hina Khan, Julia Judd, Joanne Xiu, Asad Ullah, Girindra Raval, Patrick Ma, Jorge Nieva, Milan Radovich, Matthew Oberley, So Yeon Kim,
Hirva Mamdani, Luis Raez, Ari Vanderwalde, Balasz Halmos, Hossein Borghaei, Stephen Liu, Nagla Abdel Karim
We report a large real-world dataset evaluating outcomes with check-point inhibitors in NSCLCs withKRAS and specific co-mts. Across the subgroups, KKL (KRAS mt/STK-11 mt/KEAP-1 mt) demonstrated universally poor outcomes in all KRASsubtypes; irrespective of PD-L1 expression.
Among all KRAS co-mutant groups, K-only NSCLC tumors showed the best prognosis, followed by KL and KP groups while KKL showed the worst outcome.
In the PD-L1 <1% group, KP group showed worse outcome than K-only however comparable outcomes to K-only in PD-L1 positive (TPS ≥1%).
Interestingly, positive TPS score was not associated with significantly improved outcome in the molecular groups investigated and was in fact, associated with worse outcome in KKL. Pts with KKL co-mts have adverse post-IO outcomes in TPS ≥1% but favorable in TPS <1%.
These observations emphasize that co-mutation patterns have a clear association with clinical outcomes inKRAS-mt NSCLC and must be used in predictive models for individualized therapy while the role of PD-L1 score may be limited in KRAS-mt NSCLC.