NEW YORK – In updated guidelines last week, the National Comprehensive Cancer Network (NCCN) added two KRAS inhibitors, Mirati Therapeutics' Krazati (adagrasib) and Amgen's Lumakras (sotorasib), as options for previously treated patients with KRAS G12C-mutated pancreatic cancer.
Both Krazati and Lumakras are presently approved in the US for patients with previously treated, locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations. The NCCN is now recommending these drugs for some pancreatic cancer patients after they showed promising activity in clinical trials in this setting.
In April, researchers presented data from the Phase II KRYSTAL-1 trial, in which there was a 33 percent response rate among 21 patients with KRAS G12C-mutant pancreatic cancer on Krazati. Amgen presented data last year from the Phase I/II CodeBreaK 100 trial, showing a 21 percent response rate among 38 evaluable KRAS G12C-mutant pancreatic cancer patients on Lumakras.
The NCCN's Clinical Practice Guidelines in Oncology are intended to help healthcare providers make cancer care decisions based on the latest evidence. The group noted in the latest update that both Krazati and Lumakras were useful in certain circumstances for advanced or metastatic patients who have good, intermediate, or poor performance status and are positive for a KRAS G12C mutation. The recommendations for patients with poor performance status were based upon lower-level evidence, but NCCN said there was expert consensus that the intervention is appropriate.
In March, the NCCN also added Krazati to its lung cancer treatment guidelines as an option for KRAS G12C-mutant NSCLC patients with central nervous system (CNS) metastases.