The Impact of Real-World Data Analysis of Patients with Advanced NSCLC Harboring KRAS Mutations

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Globally, lung cancer is the most common cancer, accounting for more than 2 million cases in 2018. Non–small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, accounting for 85% of all lung cancer cases. Although there have been considerable advances in treatment for NSCLC, the overall 5-year survival rate for patients with advanced NSCLC is 15% to 21%. The Kirsten rat sarcoma (KRAS) gene is more commonly found in smokers than nonsmokers and is the most common oncogenic driver of NSCLC, occurring in up to 40% of all NSCLC cases. The KRAS G12C mutation is the most common mutation subtype and is found in approximately 11% of all NSCLC cases. At the time of this publication, there was no approved targeted therapy for KRAS mutations; however, 1 KRAS inhibitor is currently approved for use in the United States.

In an article in Lung Cancer, the results of an evaluation of a real-world cohort of German patients with KRAS G12C–mutated advanced NSCLC were released. Germany’s CRISP registry collects representative, nationwide data on NSCLC. In this analysis, the treatment regimen, current treatment status, best response, the PD-L1 expression, and the outcome of patients with the KRAS wild-type mutation, KRAS G12C mutation, and KRAS non-G12C mutations were presented. There were 1039 patients recruited to the registry from 98 centers in Germany. All patients were aged ≥18 years with stage IV or stage IIB histologically confirmed NSCLC and were ineligible for curative surgery and/or radiochemotherapy.

When the KRAS mutation was examined, the KRAS G12C mutation was found in 160 patients, non-G12C mutation was found in 251 patients, and KRAS wild-type mutation was found in 628 patients. High PD-L1 expression was documented in 43.5% of patients with the KRAS G12C mutation, 28.9% of patients with non-G12C mutation, and 28% of patients with KRAS wild-type mutation. Higher PD-L1 expression was associated with a significantly lower risk of mortality.

Treatment regimen analysis found 89.3% of patients with the KRAS G12C mutation, 87.7% of patients with a non-G12C mutation, and 68.8% of patients with KRAS wild-type mutation had first-line treatment combined with an immune checkpoint inhibitor during the study period. Median first-line treatment duration of patients who completed first-line treatment was 75 days for patients with G12C mutation, 94 days for patients with non-G12C mutation, 79 days for patients with wild-type nonsquamous mutation, and 86 days for those with wild-type squamous mutation. Disease progression was the most common cause for ending the treatment. Few patients (n = 7) experienced a complete response. There was no clinical outcome difference among the mutation subtypes.


Sebastian M, Eberhardt WEE, Hoffknecht P, et al. KRAS G12C-mutated advanced non-small cell lung cancer: a real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315). Lung Cancer. 2021;154:51-61.

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