CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer
The first KRAS-blocking pill shrank tumours in about one in five patients with heavily pretreated pancreatic cancer carrying the G12C mutation and controlled the disease in most for a few months. Modest as that is, it was the first direct hit on the gene that drives nearly every pancreatic cancer.
Overview
Phase 1 and 2 single-arm cohorts of the CodeBreaK 100 trial in 38 patients with KRAS p.G12C-mutated metastatic pancreatic ductal adenocarcinoma who had received at least one prior systemic therapy (most had received two or more), treated with sotorasib 960 mg once daily.
The confirmed objective response rate was 21 percent and disease control about 84 percent; median progression-free survival was 4.0 months and median overall survival 6.9 months. Treatment-related grade 3 adverse events occurred in about one in six patients, mainly diarrhoea and fatigue, with no fatal events.
- Objective response 21 percent; disease control about 84 percent.
- Median progression-free survival 4.0 months and median overall survival 6.9 months.
Sotorasib is a guideline-listed later-line option for the 1 to 2 percent of pancreatic cancers with KRAS G12C, and the proof that KRAS in pancreatic cancer is druggable; the larger opportunity lies with inhibitors of G12D and pan-RAS drugs.
- A small single-arm cohort with no comparator; the response rate is far below that seen in lung cancer.
- Responses were short, and resistance mechanisms in pancreatic cancer are only partly described.
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