Posted: Tuesday, July 18, 2023
A group of researchers evaluated the efficacy of the KRAS inhibitor adagrasib in the treatment of patients with an assortment of solid tumors, including biliary tract cancer, containing KRAS G12C mutations in the phase I/II KRYSTAL-1 trial. According to the study findings, which were presented during the April 2023 session of the American Society for Clinical Oncology (ASCO) Plenary Series (Abstract 425082), adagrasib was active in previously treated patients.
“Adagrasib monotherapy demonstrated clinically meaningful activity in a variety of KRAS G12C–mutated solid tumors, for which no standard-of-care treatment options are available,” stated Shubham Pant, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, in an article in The ASCO Post. “The clinical activity of adagrasib in patients with pancreatic and biliary tract cancers is noteworthy, as chemotherapy has limited clinical activity in these patient populations in the second-line setting.” For more from Dr. Pant on this agent, see this JNCCN 360 video.
The report here focused on a phase II cohort of patients with unresectable or metastatic KRAS G12C–mutated solid tumors receiving adagrasib monotherapy. This arm of the study followed 64 patients with various types of KRAS-mutated cancers, of whom 34% had received at least three prior lines of systemic therapy. The disease control rate after approximately 17 months was 86.0%, and the median duration of response was 5.3 months. The median progression-free survival was 7.4 months, and the median overall survival was 14.0 months.
Treatment-related adverse events were observed in 96.8% of patients but mostly consisted of symptoms such as nausea, diarrhea, fatigue, and vomiting. Some of these effects led to dose reductions and interruptions in certain patients, but no patient discontinued treatment as a result of toxicity, the investigators reported.
Disclosure: Dr. Pant has served as a consultant or advisor to Ipsen, Janssen, Novartis, and Zymeworks and has received institutional research funding from numerous sources.