Treatment outcomes and clinical characteristics of patients with KRAS-G12C-mutant non-small cell lung cancer Journal Article


Authors: Arbour, K. C.; Rizvi, H.; Plodkowski, A. J.; Hellmann, M. D.; Knezevic, A.; Heller, G.; Yu, H. A.; Ladanyi, M.; Kris, M. G.; Arcila, M. E.; Rudin, C. M.; Lito, P.; Riely, G. J.
Article Title: Treatment outcomes and clinical characteristics of patients with KRAS-G12C-mutant non-small cell lung cancer
Abstract: PURPOSE: KRAS 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 DESIGN: Through 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. RESULTS: We 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). CONCLUSIONS: We 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.
Journal Title: Clinical Cancer Research
Volume: 27
Issue: 8
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2021-04-15
Start Page: 2209
End Page: 2215
Language: English
DOI: 10.1158/1078-0432.Ccr-20-4023
PUBMED: 33558425
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Glenn Heller
    368 Heller
  2. Helena Alexandra Yu
    160 Yu
  3. Piro Lito
    31 Lito
  4. Marc Ladanyi
    1124 Ladanyi
  5. Gregory J Riely
    458 Riely
  6. Maria Eugenia Arcila
    517 Arcila
  7. Mark Kris
    766 Kris
  8. Matthew David Hellmann
    326 Hellmann
  9. Charles Rudin
    294 Rudin
  10. Kathryn Cecilia Arbour
    51 Arbour
  11. Hira Abbas Rizvi
    79 Rizvi