Adagrasib shows antitumour activity in KRAS G12C-mutant colorectal cancer

Adagrasib appears to have some effect against metastatic, KRAS G12C-mutated colorectal cancer when used in treatment-experienced patients either as oral monotherapy or in combination with cetuximab, according to the results of a phase I-II, open-label study.

A total of 76 heavily pretreated patients with metastatic colorectal cancer with KRAS G12C mutation were included. They were randomized to receive adagrasib 600 mg orally twice daily alone or in combination with intravenous cetuximab once a week (with an initial loading dose of 400 mg per square meter of body-surface area, followed by a dose of 250 mg per square meter) or every 2 weeks (with a dose of 500 mg per square metre).

Of the patients, 44 received adagrasib as a monotherapy while 32 received it in combination with cetuximab, with a median follow-up of 20.1 months and 17.5 months, respectively. In the monotherapy group (43 evaluable patients), 19 percent of patients (95 percent confidence interval [CI], 8–33) showed response to treatment with a median response duration of 4.3 months (95 percent CI, 2.3–8.3). The median progression-free survival (PFS) was 5.6 months (95 percent CI, 4.1–8.3).

In the combination-therapy group (28 evaluable patients), on the other hand, 46 percent of patients (95 percent CI, 28–66) responded to treatment with a median response duration of 7.6 months (95 percent CI, 5.7 to not estimable). The median PFS was 6.9 months (95 percent CI, 5.4–8.1).

In terms of safety, the frequency of grade 3 or 4 treatment-related adverse events was 34 percent in the monotherapy group and 16 percent in the combination therapy group. None of the patients developed grade 5 adverse events.