posted on 2024-08-03, 19:00authored byRona Yaeger, Nataliya V. Uboha, Meredith S. Pelster, Tanios S. Bekaii-Saab, Minal Barve, Joel Saltzman, Joshua K. Sabari, Julio A. Peguero, Andrew Scott Paulson, Pasi A. Jänne, Marcia Cruz-Correa, Kenna Anderes, Karen Velastegui, Xiaohong Yan, Hirak Der-Torossian, Samuel J. Klempner, Scott E. Kopetz
Supplementary Figure S1. Changes from baseline in sum of target lesion diameters over time for patients continuing treatment after progression, either with adagrasib plus cetuximab (n = 38), adagrasib only (n = 10), or cetuximab only (n = 1). Only patients with available post-progression scans are included in the plot (n = 33 for adagrasib plus cetuximab; n = 1 for adagrasib only).
Funding
Mirati Therapeutics (Mirati Therapeutics Inc)
National Institutes of Health (NIH)
History
ARTICLE ABSTRACT
Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2–7.6). Median progression-free survival was 6.9 months (95% CI, 5.7–7.4) and median overall survival was 15.9 months (95% CI, 11.8–18.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3–4 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance.
Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer.This article is featured in Selected Articles from This Issue, p. 897See co-corresponding author Rona Yaeger discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606282/f27a6e46f4