• Kathryn C Arbour, Hira Rizvi, Andrew J Plodkowski, Matthew D Hellmann, Andrea Knezevic, Glenn Heller, Helena A Yu, Marc Ladanyi, Mark G Kris, Maria E Arcila, Charles M Rudin, Piro Lito, and Gregory J Riely.
• Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. arbourk@mskcc.org.
• Clin Cancer Res. 2021 Apr 15; 27 (8): 2209-2215.

PurposeKRAS mutations are identified in approximately 30% of patients with non-small cell lung cancer (NSCLC). Novel direct inhibitors of KRAS G12C have shown activity in early-phase clinical trials. We hypothesized that patients with KRAS G12C mutations may have distinct clinical characteristics and responses to therapies.Experimental DesignThrough routine next-generation sequencing, we identified patients with KRAS-mutant NSCLC treated at Memorial Sloan Kettering Cancer Center (New York, NY) from 2014 to 2018 and reviewed tumor characteristics, overall survival, and treatment outcomes.ResultsWe identified 1,194 patients with KRAS-mutant NSCLC, including 770 with recurrent or metastatic disease. KRAS G12C mutations were present in 46% and KRAS non-G12C mutations in 54%. Patients with KRAS G12C had a higher tumor mutation burden (median, 8.8 vs. 7 mut/Mb; P = 0.006) and higher median PD-L1 expression (5% vs. 1%). The comutation patterns of STK11 (28% vs. 29%) and KEAP1 (23% vs. 24%) were similar. The median overall survivals from diagnosis were similar for KRAS G12C (13.4 months) and KRAS non-G12C mutations (13.1 months; P = 0.96). In patients with PD-L1 ≥50%, there was not a significant difference in response rate with single-agent immune checkpoint inhibitor for patients with KRAS G12C mutations (40% vs. 58%; P = 0.07).ConclusionsWe provide outcome data for a large series of patients with KRAS G12C-mutant NSCLC with available therapies, demonstrating that responses and duration of benefit with available therapies are similar to those seen in patients with KRAS non-G12C mutations. Strategies to incorporate new targeted therapies into the current treatment paradigm will need to consider outcomes specific to patients harboring KRAS G12C mutations.©2021 American Association for Cancer Research.

6 keywords...

hide…