Efficacy and safety of adagrasib plus cetuximab in patients with KRAS(G12C)-mutated metastatic colorectal cancer Journal Article
| Authors: | Yaeger, R.; Uboha, N. V.; Pelster, M. S.; Bekaii-Saab, T. S.; Barve, M.; Saltzman, J.; Sabari, J. K.; Peguero, J. A.; Paulson, A. S.; Jänne, P. A.; Cruz-Correa, M.; Anderes, K.; Velastegui, K.; Yan, X.; Der-Torossian, H.; Klempner, S. J.; Kopetz, S. E. |
| Article Title: | Efficacy and safety of adagrasib plus cetuximab in patients with KRAS(G12C)-mutated metastatic colorectal cancer |
| 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 inter-val [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 analy-ses 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. © 2024, American Association for Cancer Research Inc.. All rights reserved. |
| Keywords: | adult; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; major clinical study; genetics; mutation; clinical trial; drug efficacy; drug safety; drug withdrawal; monotherapy; nuclear magnetic resonance imaging; follow up; antineoplastic agent; genetic analysis; metastasis; progression free survival; computer assisted tomography; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; pathology; pyrimidines; oncology; cetuximab; irinotecan; colorectal neoplasms; tumor suppressor gene; multicenter study; colorectal tumor; neoplasm metastasis; phase 3 clinical trial; pathogenicity; piperazines; drug therapy; point mutation; toxicity; oxaliplatin; piperazine derivative; pyrimidine derivative; protein p21; proto-oncogene proteins p21(ras); fluoropyrimidine; b raf kinase; kras protein, human; brain derived neurotrophic factor receptor; adverse event; metastatic colorectal cancer; estimated glomerular filtration rate; very elderly; humans; human; male; female; article; droplet digital polymerase chain reaction; sodium glucose cotransporter 2 inhibitor; adagrasib; acetonitriles; acetonitrile derivative; kras mutated metastatic colorectal cancer |
| Journal Title: | Cancer Discovery |
| Volume: | 14 |
| Issue: | 6 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-06-01 |
| Start Page: | 982 |
| End Page: | 993 |
| Language: | English |
| DOI: | 10.1158/2159-8290.Cd-24-0217 |
| PUBMED: | 38587856 |
| PROVIDER: | scopus |
| PMCID: | PMC11152245 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
