KRAS is a commonly mutated gene in pancreatic cancer and is known as an impregnable gene for cancer therapy. KRAS mutations are very common in many gastrointestinal cancers, including colorectal, biliary, and other GI cancers, but no targeted therapies have been developed for decades.

But times are changing. Recently, therapies targeting specific mutations in KRAS have been developed and are actively in clinical trials. One example is sotorasib, a KRAS G12C inhibitor. Because KRAS G12C is not frequently seen in pancreatic cancer, only phase 1/2 studies have been conducted, but the results have been encouraging.

In the codeBreaK100 study, which enrolled 38 patients, sotorasib showed a 21% objective response rate in pancreatic cancer patients with KRAS G12C, meaning that 21% of patients had a reduction in tumor size of 30% or more. This is an excellent response rate considering that the study enrolled patients who had received two or more prior therapies, and therefore had little hope with standard of care. Median progression-free survival was 4 months and median overall survival was approximately 7 months. There were no serious adverse events requiring treatment discontinuation.

While still limited, it is good to see that a targeted therapy has been developed that targets the KRAS G12C mutation. We look forward to seeing how this translates into the clinic.