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JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.

Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Author information

1
University of California, San Francisco.
2
Department of Biostatistics and Bioinformatics and Alliance Statistics and Data Center, Duke University Medical Center, Durham, North Carolina.
3
University of Southern California, Los Angeles.
4
University of North Carolina at Chapel Hill.
5
Alliance Statistics and Data Center, Mayo Clinic Cancer Center, Rochester, Minnesota.
6
Dana-Farber/Partners CancerCare, Boston, Massachusetts.
7
Indiana University, Simon Cancer Center, Indianapolis.
8
National Surgical Adjuvant Breast and Bowel Project/NRG Oncology, and Southeastern Medical Oncology Center, Goldsboro, North Carolina.
9
Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada.
10
University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
11
Memorial Sloan Kettering Cancer Center, New York, New York.
12
Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus.
13
Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.
14
American Society of Clinical Oncology, Alexandria, Virginia.
15
Brigham and Women's Hospital, Boston, Massachusetts.
16
Lenoir Memorial Hospital/Kinston Medical Specialists PA, Kinston, North Carolina.
17
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
18
University of Wisconsin, Madison.
19
Southwest Oncology Group Chair's Office and Knight Cancer Institute, Oregon Health & Science University, Portland.

Abstract

Importance:

Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.

Objective:

To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer.

Design, Setting, and Participants:

Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015.

Interventions:

Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient.

Main Outcomes and Measures:

The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response.

Results:

Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13).

Conclusions and Relevance:

Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.

Trial Registration:

clinicaltrials.gov identifier: NCT00265850.

PMID:
28632865
PMCID:
PMC5545896
DOI:
10.1001/jama.2017.7105
[Indexed for MEDLINE]
Free PMC Article

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