NCCN Recommends Krazati for Treatment of Pancreatic Cancer Subset


The National Comprehensive Cancer Network updated its recommendations to include Krazati for patients with KRAS G12-mutant pancreatic cancer.


The NCCN now recommends Krazati for certain patients with pancreatic cancer.

The National Comprehensive Cancer Network (NCCN) now recommends Krazati (adagrasib) for the treatment of patients with KRAS G12-mutant pancreatic cancer.

“The NCCN Guidelines are the most thorough and frequently updated clinical practice guidelines available in any area of medicine, and updates are intended to reflect rapid advancements in the field of cancer research and management,” Dr. Shubham Pant, associate professor in the department of gastrointestinal medical oncology with a joint appointment in the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, said in an interview with CURE®, noting that medications that are recommended by the NCCN are more likely to be covered by health insurance.

Pant gave CURE an overview of the use of Krazati for this subset of patients, and the promising research behind the drug.

Can you give a bit of background on the use of Krazati for KRAS G12C-mutant pancreatic cancer?

Pancreatic cancer is an aggressive form of cancer that is notoriously resistant to treatment and the growth of pancreatic cancer may be driven by a mutated gene called KRASG12C. (Krazati) is a targeted therapy that inhibits the KRAS G12C mutation and was recently approved for use in previously treated adults with advanced non-small cell lung cancer (NSCLC) with the KRASG12C mutation.

(Krazati) is currently being evaluated in a phase 2 KRYSTAL-1 trial for use in KRASG12C-mutated unresectable or metastatic pancreatic cancer and other solid tumors.

At the (American Society of Clinical Oncology) Plenary Series session, we presented updated clinical data from the largest phase 2 dataset evaluating unresectable or metastatic KRAS G12C mutated solid tumors excluding NSCLC and colorectal cancer. These data represent an investigational use of (Krazati) and so the efficacy and safety of (Krazati) for this investigational use has not been approved by the FDA. The (57) patients with measurable disease at baseline reported an objective response rate (percentage of patients whose disease shrinks or disappears from treatment) of 35% for the overall cohort. In patients with pancreatic cancer, (objective response rate) was 33% (seven of 21 patients). The historically reported standard of care for previously treated, advanced (pancreatic ductal adenocarcinoma) has a reported objective response rate of 3 to 17%.The safety profile of (Krazati) was consistent with previously reported data in patients with pretreated advanced KRASG12C-mutated NSCLC and CRC.

The most common treatment-related (side effects) that occurred with (Krazati) in this study included nausea, diarrhea, fatigue and vomiting, which were generally low grade. Results were also published in the Journal of Clinical Oncology as a Rapid Communication which are reserved for publications deemed to represent timely and late-breaking research that may have an immediate impact on patient care.

What are the NCCN Guidelines, and how are they crafted?

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) provide recommendations for the prevention, diagnosis and management of cancer care and are intended to assist all individuals who impact decision-making in cancer care including physicians, nurses, pharmacists, payers, patients and their families, and many others.

What do patients with pancreatic cancer need to know about (Krazati)?

Patients with pancreatic cancer and their oncologists should know that (Krazati) is being studied as a potential therapy targeted for KRASG12C-mutated cancers and, based on phase 2 data from the KRYSTAL-1 trial, appears to exhibit clinical activity. Biomarker testing is necessary to identify potential treatment targets, and testing for KRAS G12C mutation is critical to identify patients who may benefit from treatment with (Krazati).

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