ASCO Expert Perspective
“This single-agent phase 1/2 data from the KRYSTAL-1 study suggests that, in patients with previously treated pancreatic or biliary tract cancers, adagrasib showed a promising response rate and progression-free survival with good tolerance of therapy. This phase 1/2 study will need to be validated in a larger sample size.”
– Cathy Eng, MD, FACP, FASCO, ASCO Expert in Gastrointestinal Cancers
In patients with KRASG12C mutated cancers, adagrasib, an oral drug that targets KRASG12C, may be an effective treatment, according to research that will be presented during the April 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series.
KRAS is a gene that makes a protein that regulates cell growth and is one of the most frequently mutated genes known to cause cancer. When a mutation - or error - in this gene occurs, cells can grow uncontrollably leading to cancer growth and metastases. A common KRAS mutation, G12C (KRASG12C), occurs in 2% of pancreatic cancers, and 1% of biliary tract cancers.1 There are currently no approved targeted treatment options are available for KRASG12C-driven solid tumors other than NSCLC.
In the phase 1/2 KRYSTAL-1 study, 63 patients with KRASG12C-mutated solid tumors – including pancreatic ductal adenocarcinoma, biliary tract cancers, other gastrointestinal (GI), and non-GI tumors – were treated with adagrasib. Among 57 patients with measurable disease, overall response rate (ORR) was 35.1%, disease control rate was 86%, median duration of response was 5.3 months, median progression-free survival (PFS) was 7.4 months, and median overall survival (OS) was 14 months. Among 21 patients with pancreatic ductal adenocarcinoma, ORR was 33.3%, disease control rate was 81.%, median PFS was 5.4 months, and median OS was 8 months. Among 12 patients with biliary tract cancers, ORR was 41.7%, disease control rate was 91.7%, median PFS was 8.6 months, and median OS was 15.1 months. Approximately 97% of patients experienced treatment-related adverse events, with grade 3 events observed in 25.4% of patients and grade 4 events in 1.6% of patients. No grade 5 events occurred.
The authors note that biomarker testing in tumors is important to identify certain mutations that can cause the tumor to grow and help physicians determine the best treatment for a patient.
“Our study demonstrates that adagrasib has clinical activity across a broad range of KRASG12C-mutated tumors, including pancreatic and biliary tract cancers, and observed a response rate of 35% in patients who have no standard-of-care treatment available to them or have declined available therapies,” said Shubham Pant, MD, MBBS, from the University of Texas MD Anderson Cancer Center and lead author of the study.
Abstract and presentation will be available here on April 20, 2023 at 3:00 PM (ET).
View the author disclosures: https://coi.asco.org/Report/ViewAbstractCOI?id=425082
View the disclosures for Dr. Eng: https://coi.asco.org/share/U5V-NT84/Eng%2c%20Cathy
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