A nationwide, prospective, observational cohort has been developed with a goal to characterize the treatment of patients with KRAS-mutant non-small cell lung cancer (NSCLC) before and after the likely future approval of KRAS inhibitors, according to a report published in Lung Cancer.1

 “Prospectively collected molecularly stratified outcome data from large cohorts in routine care are of high relevance,” the authors wrote. Multiple KRAS inhibitors have entered clinical trials and could enter the clinic in the near future. The aim of the CRISP registry was to develop a cohort to characterize the potential role of KRAS inhibitors and, if they are approved in the future, the treatment reality before and after their use.

The CRISP registry is a noninterventional, prospective, multicenter, observational cohort of 1039 patients with stage IIIB or stage IV NSCLC that is either wild type for actionable alterations or harbors KRAS mutations. Patients were recruited between 2015 and 2019 from multiple centers in Germany. Data collected include type of KRAS mutation, treatment, response, and outcomes.

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The cohort includes 39.6% of patients with a KRAS mutation, including 15.4% with the G12C mutation and 24.2% with other KRAS mutations such as G12V (21.2%), G12D (13.9%), and G12A (9.5%). The remaining patients had wild-type KRAS.

Among patients with wild-type KRAS, G12C mutations, and other KRAS mutations, tumor expression of programmed death-ligand 1 (PD-L1) was more than 50% among 28.0%, 43.5%, and 28.9%, respectively. The first-line treatment was an immune checkpoint inhibitor-based regimen for 68.8%, 89.3%, and 87.7% of patients with wild-type, G12C mutations, or other KRAS mutations, respectively. The majority of patients who received chemotherapy as first-line therapy were treated with an immune checkpoint inhibitor as their second-line treatment.

Clinical outcomes were similar among patients with differing KRAS status, with a median progression-free survival of 5.4 to 5.7 months. Among patients with wild-type KRAS, the median overall survival (OS) was 11.6 months for those with nonsquamous histology and 15.8 months for those with squamous histology. For patients with KRAS mutations, the median OS was 11.6 months with the G12C mutation and 10.4 months with other mutations.

Multivariate analysis demonstrated that better Eastern Cooperative Oncology Group performance status and PD-L1 expression greater than 50% were associated with lower risk of overall mortality.

The authors concluded that “the present data on 160 patients with KRAS G12C mutations recruited by the CRISP registry in routine care might be of major importance for the lung cancer therapists as well as historical controls on treatment and outcome of this patient subgroup.”


Sebastian M, Eberhardt WEE, Hoffknecht P, et al; the CRISP Registry Group. 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. doi:10.1016/j.lungcan.2021.02.005