Abstract #LBA10: Melissa L. Johnson presented the primaryanalysis of the P3 CodeBreaK 200 trial. The trial compared sotorasib (n=169) vs docetaxel(n=151) in KRAS G12C-mutated NSCLC patients who progressed after prior platinum-based chemotherapy and a checkpoint inhibitor.
Results: Met primary endpoint of a statistically significant improvement in PFS with sotorasib vs docetaxel. One-year PFS was 24.8% vs 10.1% forsotorasib vs docetaxel, respectively. Met key secondary endpoints:Sotorasib significantly improved ORR (28.1% vs 13.2%) and DCR (82.5%vs 60.3%) vs docetaxel. OS was not significantly different between treatment arms, though the trial was not powered for OS. Sotorasib had fewer Grade ≥3 AEs than docetaxel (33.1% vs 40.4%).
Thought leader opinions on these results are mixed.While the trial met its primary endpoint, many thought leaders consider sotorasib’s benefit in this trial modest
Several commentators were disappointed by the poor OSbenefit and felt it may prompt reimbursement challenges given the expense of this targeted therapy.
A few oncologists indicated that the trial provided no meaningful information, as sotorasib was already SOC in this patient population. Docetaxel is not preferred by physicians and there are other approved combination treatments that improve OS in this patient population.
Oncologists wanted to understand if observed toxicity was due to previous treatment or to sotorasib. Detailed guidelines for AE management were requested.
Summary: Preliminary data from the CodeBreaK 200 trial shows that sotorasib provides significant PFS, ORR, and DCR benefit over docetaxel with fewer AEs. However, thought leaders largely consider these results disappointing, as sotorasib was expected to perform better – for instance, no OS benefit was demonstrated. In addition, there are widespread concerns surrounding toxicity and cost.
Synthesis by Opus Strategy, LLC