Loading
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.
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.
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.
Shares Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, KRAS G12C-mutant pancreatic ductal adenocarcinoma, Sotorasib, KRAS & RAS inhibitors.
Shares KRAS G12C, RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, KRAS mutation subtypes (G12C, G12D, G12V), KRAS & RAS inhibitors.
Shares Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable, KRAS mutation subtypes (G12C, G12D, G12V), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, RAS / RAF / MEK / ERK (MAPK).
Shares KRAS G12C, KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS & RAS inhibitors, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares KRAS G12C, Sotorasib, KRAS & RAS inhibitors, RAS / RAF / MEK / ERK (MAPK).
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, KRAS G12C-mutant pancreatic ductal adenocarcinoma, KRAS & RAS inhibitors, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question.
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, KRAS & RAS inhibitors, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, RAS / RAF / MEK / ERK (MAPK).
Shares RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, RAS / RAF / MEK / ERK (MAPK), KRAS.