KRAS is a gene that plays a key role in the growth and division of cells. Mutations in the KRAS gene can cause cancer, and one particular mutation called KRAS G12C occurs in about 1-2% of pancreatic cancers and 2-4% of colon cancers. These mutations make the cancer resistant to certain treatment options and are associated with a poorer prognosis. However, recent clinical trials published in NEJM January 2023 have reported promising results for two new drugs, Adagrasib and Sotorasib, that target the KRAS G12C mutation specifically.
Adagrasib is an oral small-molecule inhibitor that was tested in a phase 1-2 trial for the treatment of metastatic colorectal cancer with KRAS G12C mutations. The trial included 44 patients who received Adagrasib monotherapy and 32 patients who received Adagrasib in combination with cetuximab, a chemotherapy drug. The results showed that 46% of patients in the combination therapy group had a response, with a median response duration of 7.6 months and a median progression-free survival of 6.9 months. The percentage of grade 3 or 4 treatment-related adverse events was 16% in the combination therapy group and there were no grade 5 adverse events. These results suggest that Adagrasib may be a promising option for the treatment of KRAS G12C-mutated colon cancer, particularly when combined with cetuximab.
Sotorasib is a KRAS G12C inhibitor that was tested in a phase 1-2 trial for the treatment of pancreatic cancer in patients who had received at least one previous systemic therapy. The trial included 38 patients withKRAS G12C-mutated pancreatic cancer, all of whom received Sotorasib at a dose of 960 mg orally once daily. The results showed that 8 patients (21%) had a centrally confirmed objective response, with a median progression-free survival of 4.0 months and a median overall survival of 6.9 months. Treatment-related adverse events were reported in 42% of patients, with 6 patients (16%) experiencing grade 3 adverse events. No treatment- related adverse events were fatal or led to treatment discontinuation. These results suggest that Sotorasib may have anticancer activity and an acceptable safety profile in the treatment ofKRAS G12C-mutated pancreatic cancer.
These recent clinical trial results for Adagrasib and Sotorasib provide new hope for the treatment of KRAS G12C-mutated cancers, particularly pancreatic and colon cancer. These drugs target the KRAS G12C mutation specifically, which may make them more effective against cancers that are resistant to other treatments. Further research is needed to confirm the efficacy and safety of these drugs and to determine the optimal dosing and combination regimens. However, these initial results are encouraging and suggest that Adagrasib and Sotorasib may represent a promising new option for the treatment of KRAS G12C-mutated cancers.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.