Adagrasib improves PFS over docetaxel in previously treated KRAS G12C-mutated NSCLC

MedNet.nl: Treatment with adagrasib leads to a statistically significant and clinically meaningful improvement in progression-free survival and objective response rate compared with docetaxel in patients with previously treated KRAS G12C-mutated NSCLC. This is evident from the primary analysis of the KRYSTAL-12 trial. That adagrasib is an effective treatment for KRAS G12C-mutated NSCLC was previously suggested by the results of the phase 2 KRYSTAL-1 study. The phase 3 KRYSTAL-12 study aimed to confirm these findings. The study compared adagrasib with docetaxel in patients with advanced KRAS G12C-mutated NSCLC who had previously been treated with chemotherapy and immunotherapy. For the study, 453 patients were randomized 2:1 to adagrasib (n=301) and docetaxel (n=152). The primary endpoint was progression-free survival (PFS). After a median follow-up of 7.2 months, the PFS determined by an independent committee was significantly better when treated with adagrasib. The median PFS in the adagrasib and docetaxel arms was 5.5 versus 3.8 months (HR=0.58). After 6 months, 45% and 30% of patients were progression-free, respectively. In most subgroups, there was a clear advantage of adagrasib over docetaxel. The objective response rate (ORR) in both groups was 32% versus 9%, respectively, and the median duration of response was 8.3 versus 5.4 months. The depth of response was also markedly better with treatment with adagrasib, the researchers emphasized. The intracranial response rate in both groups was 24% versus 11%, respectively, with one complete response in the adagrasib arm. In a separate subgroup of patients with one target lesion in the brain and at least one post-baseline measurement, the intracranial ORR was 40%. In terms of adverse events, the incidence of adverse events of grade 3 or higher was similar, at 47% versus 46%. However, fewer patients discontinued adagrasib because of adverse events (8 vs 14%). The researchers state that adagrasib is an effective treatment option in patients with previously treated KRAS G12C-mutated locally advanced or metastatic NSCLC. Mok TSK, Yao W, Duruisseaux M, et al. KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation. ASCO 2024, abstract LBA8509. Jänne P, Riely GJ, Gadgeel SM, et al. Adagrasib in non-small-cell lung cancer harboring a KRAS G12C mutation. N Engl J Med 2022;387:120-31. This article was originally published in Dutch on MedNet.nl

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Adagrasib improves PFS over docetaxel in previously treated KRAS G12C-mutated NSCLC

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