No Improvement in Overall Survival Between Patients with KRAS G12C NSCLC and Patients with non-KRAS G12C NSCLC

Lung cancer is the most common cause of cancer-related mortality worldwide with non–small-cell lung cancer (NSCLC) accounting for 85% of all cases.¹ Kirsten rat sarcoma viral oncogene (KRAS) is a common mutation in NSCLC, accounting for 20% of all NSCLC cases. KRAS mutations are related to tobacco exposure, with only 5% of KRAS mutations found in light smokers or people who have never smoked.¹ NSCLC cancer which harbors the KRAS mutation has a poor response to chemotherapy as KRAS mutation has the ability to alter the tumor microenvironment.¹ The most common KRAS mutation occurs on codon 12.¹ These mutations are associated with a poor overall patient prognosis, but with the development and use of immunotherapy, clinical outcomes for patients with KRAS-mutant NSCLC has improved.¹

To evaluate the clinical outcomes of patients with KRAS-harboring NSCLC treated with immunotherapy, a retrospective study was performed using data from 120 patients treated at the Catalan Institute of Oncology in Badalona, Spain between 2013 and 2020. The cobas® KRAS mutation test was used to determine the KRAS status of these patients. This real-time PCR test detects mutations in codons 12, 13, and 61 of the KRAS gene. The cases in 2020 had KRAS status determined by next-generation sequencing. In addition to determining KRAS mutation, the patient’s PD-L1 status was determined and categorized as negative (<1%,) low (1%-49%), and high (50%-100%).

The median patient age at diagnosis was 63 years and 75% of all patients were male. Current or former smokers made up 96% of the patient cohort. Stage IV lung adenocarcinoma was present at first diagnosis for 74% of the patients and KRAS status was determined for 107 patients. When KRAS and PD-L1 were analyzed, 46% had KRAS G12C, 54% had non-G12C, and high PD-L1 was found in 37% of cases. The majority of the high PD-L1 cases were in KRAS G12C cases. Immunotherapy was instituted for 65 patients: 42% of these patients had immunotherapy as first-line therapy, 46% had it as second-line therapy, and 12% received immunotherapy as third-line therapy. Anti–PD-1 therapy was given to 81% of patients and 3% had anti–CTLA-4 therapy. Median progression-free survival to immunotherapy was 10.1 months for patients with KRAS G12C and 3.3 months for non-G12C (P = .07). Median overall survival for patients with KRAS G12C was 17.9 months and 18.6 months for patients with non-G12C KRAS (P = .13).

Source

Notario Rincon L, Pous A, López-Paradís A, et al. The immunotherapy role in patients (pt) with KRAS mutated metastatic non-small cell lung cancer (NSCLC): differences between KRAS G12C and non-G12C. Ann Oncol. 2022;33:s50.

Reference

1. Xie M, Xu X, Fan Y. KRAS-mutant non-small cell lung cancer: an emerging promisingly treatable subgroup. Front Oncol. 2021;11:672612.