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22-09-2022 | ESMO 2022 | Conference coverage | News

CodeBreaK 200 data support sotorasib for KRAS G12C-mutated NSCLC

Author: Laura Cowen


medwireNews: Patients with previously treated KRAS G12C-mutated advanced non-small-cell lung cancer (NSCLC) have significantly better progression-free survival (PFS) and objective response rates (ORRs) with sotorasib than with docetaxel, research shows.

The CodeBreaK 200 trial, which was the first randomized phase 3 trial of a KRAS G12C inhibitor, also showed that sotorasib “had a more favorable safety profile,” than docetaxel, reported Melissa Johnson (Sarah Cannon Research Institute, Tennessee, Nashville, USA) at the ESMO Congress 2022 in Paris, France.

She told delegates that the “findings support sotorasib as an important treatment option in this setting and reinforce the importance of [next-generation sequencing] testing for KRAS G12C.”

For the trial, 345 individuals with KRAS G12C-mutated NSCLC that had progressed after platinum-based chemotherapy and a checkpoint inhibitor were randomly assigned to receive oral sotorasib 960 mg/day (n=171) or intravenous docetaxel 75 mg/m2 every 3 weeks (n=174). Patients with active brain metastases were excluded from the study.

After a median 17.7 months of follow-up, median PFS was 5.6 months in the sotorasib group and 4.3 months in the docetaxel group, giving a statistically significant hazard ratio of 0.66 in favor of sotorasib.

At 1-year the PFS rate was 24.8% with sotorasib and 10.1% with docetaxel, and Johnson noted that the PFS benefit was consistent across subgroups.

The ORR was also significantly higher with sotorasib than with docetaxel, at 28.1% versus 13.2%, and the disease control rates were a corresponding 82.5% and 60.3%.

Furthermore, individuals in the sotorasib arm had a faster median time to response than those in the docetaxel arm (1.4 vs 2.8 months) and a longer median duration of response (8.6 vs 6.8 months).

Overall survival (OS) did not differ significantly between the two treatment arms, at medians of 10.6 and 11.3 months with sotorasib and docetaxel, respectively. However, Johnson pointed out that the study was not adequately powered to detect OS differences and that 34% of participants in the docetaxel group subsequently received a KRAS G12C inhibitor

Among the patient-reported outcomes analyzed, the researchers found that the time to deterioration in global health status, physical functioning, and cancer-related symptoms (dyspnea and cough) were significantly delayed with sotorasib relative to docetaxel.

Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 33.1% of participants who received sotorasib and 40.4% of those given docetaxel, with serious TRAEs reported in a respective 10.7% and 22.5%. There was one treatment-related death in the sotorasib arm and two in the docetaxel arm.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

ESMO Congress 2022; Paris, France: 9–13 September