Cancers (Oct 2022)

Clinical and Molecular Features of KRAS-Mutated Lung Cancer Patients Treated with Immune Checkpoint Inhibitors

  • Dan Zhao,
  • Haiqing Li,
  • Isa Mambetsariev,
  • Tamara Mirzapoiazova,
  • Chen Chen,
  • Jeremy Fricke,
  • Prakash Kulkarni,
  • Victoria Villaflor,
  • Leonidas Arvanitis,
  • Stanley Hamilton,
  • Michelle Afkhami,
  • Raju Pillai,
  • Brian Armstrong,
  • Loretta Erhunmwunsee,
  • Erminia Massarelli,
  • Martin Sattler,
  • Arya Amini,
  • Ravi Salgia

DOI
https://doi.org/10.3390/cancers14194933
Journal volume & issue
Vol. 14, no. 19
p. 4933

Abstract

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Background: The molecular and clinical features of KRAS-mutated lung cancer patients treated with immunotherapy have yet to be characterized, which could guide the development of therapeutics targeting KRAS with potential immuno-oncology treatment combinations. Research Question: Do KRAS-mutated patients with different subtypes and comutations have different clinical responses and overall survival (OS) to checkpoint inhibitors? Study Design and Methods: 87 patients with NSCLC at the City of Hope who received immune checkpoint inhibitors were identified and analyzed retrospectively. Tumor genomic alterations were extracted from the clinical data with next-generation sequencing using various platforms. Demographic, clinical, molecular, and pathological information was collected with the approval of the institutional review board of the City of Hope. OS was calculated if it was available at the study time point, and responses were determined according to the RECIST v1.1. Results: Among 87 patients, 32 had a KRAS G12C mutation (36.8%), 19 had G12V (21.9%), 18 had G12D (20.7%), 6 had G12A (6.9%), 3 had G12R (3.45%), and 10 had amplification (11.49%) and other uncommon mutations. G12D had a statistically significant Odds Ratio (OR) between patients who had responses and progression of the disease (OR (95% CI) = 0.31 (0.09–0.95), p p = 0.185). The median OS was significantly worse with KRAS comutation CDKN2A/B loss (4.2 vs. 16.9 months, HR = 3.07 (1.09–8.69), p p < 0.01), which were included for the multivariate analysis. The OS with other KRAS comutations was not statistically significant, including STK11 and KEAP1. Conclusion: KRAS mutation subtypes such as G12D and comutations such as CDKN2/A and MET may modulate the immunotherapy responses and outcomes in lung cancer.

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