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Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis / Lung Cancer Treatments and Mutations · Journal article
Cancers · September 4, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective real-world study describes treatment patterns and outcomes in 1227 US patients with KRAS G12C-mutant advanced NSCLC initiating first-line therapy between August 2018 and December 2022. Median OS was 17.0 months overall; platinum-based chemotherapy plus pembrolizumab yielded median rwPFS of 5.3 months and OS of 12.8–15.6 months, while high PD-L1 patients on pembrolizumab monotherapy achieved median OS of 20.4–22.1 months. The data provide contemporary outcome benchmarks but lack randomised comparison and do not establish treatment superiority.
Retrospective cohort study using two linked US nationwide databases (EHR and CGDB). Patients with advanced NSCLC, KRAS G12C mutation identified by testing, and first-line therapy initiated August 2018–December 2022 in the United States. Cohort included 1227 in the EHR database and 447 in the CGDB.. Intervention: First-line therapy for advanced NSCLC; primary regimens were platinum-based chemotherapy plus pembrolizumab (46% of patients) and pembrolizumab monotherapy (20% of patients).. n = 1,227. United States (nationwide databases).
Median OS for KRAS G12C-mutant NSCLC in EHR cohort: 17.0 (95% CI 15.2–18.9) months Platinum-based chemotherapy plus pembrolizumab: median rwPFS 5.3 (4.5–7.3) months in CGDB; OS 12.8 (11.1–17.3) months in CGDB and 15.6 (12.5–18.6) months in EHR Pembrolizumab monotherapy in PD-L1 ≥50% patients: median rwPFS 4.6 (3.0–15.6) months in CGDB; OS 20.4 (10.3–38.5) months in CGDB and 22.1 (18.7–30.7) in EHR
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Clinicians treating KRAS G12C-mutant advanced NSCLC may use these real-world OS and rwPFS ranges as contemporary outcome benchmarks for patients receiving chemotherapy plus immunotherapy or single-agent immunotherapy. However, the retrospective and non-comparative design precludes firm guidance on which strategy is superior; prospective randomised trials of emerging KRAS G12C inhibitors and immunotherapy combinations are needed to improve first-line outcomes.
Retrospective real-world observational study without randomisation or concurrent control arms; provides outcome descriptors and treatment patterns but cannot establish comparative efficacy or causality for treatment strategies.
As stated by the source record.
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Clinicians treating KRAS G12C-mutant advanced NSCLC may use these real-world OS and rwPFS ranges as contemporary outcome benchmarks for patients receiving chemotherapy plus immunotherapy or single-agent immunotherapy. However, the retrospective and non-comparative design precludes firm guidance on which strategy is superior; prospective randomised trials of emerging KRAS G12C inhibitors and immunotherapy combinations are needed to improve first-line outcomes.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background: Approximately 13% of NSCLC cases have KRAS G12C mutations. As therapeutic strategies targeting KRAS G12C-mutant NSCLC evolve, it is important to understand clinical presentation and current outcomes for these patients. Methods: This retrospective study used data from two US nationwide databases, an electronic health records (EHR) database and a clinico-genomic database (CGDB) of EHR data linked to data from comprehensive genomic profiling tests. Eligible patients had advanced NSCLC, initiated first-line therapy from August 2018 to December 2022, and had KRAS test results. Clinicopathologic characteristics, treatments, real-world progression-free survival (rwPFS), and overall survival (OS) were analyzed. Results: There were 1227 patients with KRAS G12C-mutant NSCLC in the EHR database and 447 in the CGDB. First-line regimen was platinum-based chemotherapy plus pembrolizumab for 46% and pembrolizumab monotherapy for 20%. Less than 40% of patients received second-line therapy. Median (95% CI) OS for KRAS G12C-mutant NSCLC patients in the EHR was 17.0 (15.2–18.9) months. Variables significantly associated with shorter OS included PD-L1 <1%, brain metastases, STK11 co-mutation, and poor performance status. Patients treated with platinum-based chemotherapy plus pembrolizumab had median rwPFS of 5.3 (4.5–7.3) months and OS of 12.8 (11.1–17.3) months in the CGDB; median OS was 15.6 (12.5–18.6) months in the EHR. Patients with PD-L1 ≥ 50% treated with pembrolizumab monotherapy had median rwPFS of 4.6 (3.0–15.6) months and OS of 20.4 (10.3–38.5) months in the CGDB; median OS was 22.1 (18.7–30.7) in the EHR. Conclusions: These data provide a real-world benchmark of outcomes for patients with KRAS G12C-mutant NSCLC receiving the current standard of care and indicate an unmet need for more effective first-line therapies.
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