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Published on: September 30, 2016
Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer
Rona Yaeger1, Nataliya V Uboha2, Meredith S Pelster3
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
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.
Significance:
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. 897.
Insights
Adagrasib combined with cetuximab shows significant promise for treating KRASG12C-mutated colorectal cancer. This combination therapy demonstrated notable response rates and survival benefits in heavily pretreated patients.
Area of Science:
- Oncology
- Molecular targeted therapy
- Gastrointestinal cancer research
Background:
- KRASG12C mutations are prevalent in colorectal cancer (CRC).
- Targeted therapies for KRASG12C-mutated CRC are an active area of research.
- Adagrasib is a selective, irreversible KRASG12C inhibitor.
Purpose of the Study:
- To evaluate the efficacy and safety of adagrasib plus cetuximab in patients with previously treated KRASG12C-mutated metastatic colorectal cancer.
- To assess objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Analysis of the KRYSTAL-1 trial.
- Patients received adagrasib (600 mg twice daily) plus cetuximab.
- Primary endpoint: ORR by blinded independent central review.
- Median follow-up: 11.9 months.
Main Results:
- Objective response rate (ORR) was 34.0%.
- Disease control rate (DCR) was 85.1%.
- Median duration of response (DoR) was 5.8 months.
- Median progression-free survival (PFS) was 6.9 months.
- Median overall survival (OS) was 15.9 months.
- Treatment-related adverse events (TRAEs) occurred in all patients; 27.7% had grade 3-4 TRAEs.
Conclusions:
- Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with KRASG12C-mutated metastatic colorectal cancer.
- These findings support adagrasib plus cetuximab as a potential new standard of care.
- Circulating tumor DNA analysis may offer insights into treatment response and resistance mechanisms.
