Background: KRAS p.G12C mutation accounts for ̃13% of non-squamous NSCLCs and recently became a druggable target. Prior standard of care (SOC) treatment options have been limited to checkpoint inhibitors and chemotherapies as a monotherapy or combination. This US-based study provides real-world clinicopathological characteristics and outcomes of patients with KRAS p.G12C mutant aNSCLC who received 2L+ docetaxel as SOC. Methods: We conducted a retrospective observational cohort study of adult aNSCLC patients with a KRAS mutation detected via molecular testing as part of real-world care, treated with 2L+ docetaxel in the nationwide, de-identified, EHR-derived Flatiron Health (FH) database and the FH-Foundation Medicine aNSCLC clinicogenomic database between January 1, 2011–March 31, 2021. Clinicopathological and treatment characteristics were described. Median real-world overall survival (rwOS) and progression-free survival (rwPFS) were separately estimated for second, third, and fourth lines of therapy, and as any line 2L+, among eligible patients (i.e., have a minimum of 6 months opportunity for follow-up and not on a clinical trial drug). Analyses were performed for cohorts of patients with KRAS p.G12C mutation and KRAS non-p.G12C mutation, separately. Results: 677 patients with KRAS mutant aNSCLC treated with 2L+ docetaxel were included, of which 295 (44%) had KRAS p.G12C mutation. Among the 295 patients with KRAS p.G12C, mean age (SD) at advanced diagnosis was 65 (+9) years and 59% were female. The majority were White (69%) and had a history of smoking (97%), an initial diagnosis with advanced disease (78%), non-squamous cell carcinoma (96%). In total, 259 patients with KRAS p.G12C mutation were eligible for outcomes assessment. Nearly 69% of these patients initiated docetaxel in 2017 or a later year. Overall, 47% received docetaxel as second line, 35% as third line, 15% as fourth line, and 6% as a fifth or later line, with 4% receiving docetaxel in more than one line. Most (59%) docetaxel regimens were combinations, primarily with ramucirumab, and 41% were monotherapy. Nearly 68% of patients received a PD-1/PD-L1 inhibitor prior to receiving docetaxel. Outcomes are summarized in the Table. Conclusions: Real-world outcomes are poor in patients with KRAS p.G12C mutant aNSCLC treated with docetaxel in 2L or beyond, with a median OS of only 6 months. Patients with aNSCLC harboring a KRAS p.G12C mutation may benefit from available targeted treatment.

Clinicopathological and treatment characteristics, and outcomes were similar in patients with KRAS non-p.G12C mutation.