Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab in colorectal cancer Journal Article
| Authors: | Saltz, L.; Badarinath, S.; Dakhil, S.; Bienvenu, B.; Harker, W. G.; Birchfield, G.; Tokaz, L. K.; Barrera, D.; Conkling, P. R.; O'Rourke, M. A.; Richards, D. A.; Reidy, D.; Solit, D.; Vakiani, E.; Capanu, M.; Scales, A.; Zhan, F.; Boehm, K. A.; Asmar, L.; Cohn, A. |
| Article Title: | Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab in colorectal cancer |
| Abstract: | Background: Cetuximab (C), alone or with irinotecan, demonstrates activity in irinotecan-refractory colorectal cancer (CRC). Activity of 5-fluorouracil (5-FU), leucovorin (L), and bevacizumab (B), and preliminary data of cetuximab + bevacizumab, and toxicity profiles suggests that FOLF-CB (5-FU, L, C+B) may have activity with a favorable toxicity profile as first-line therapy. Methods: Eligible patients were randomized at registration to either arm A (mFOLFOX6-B) (modified, 5-FU. L (folinic acid), oxaliplatin (O) + bevacizumab), administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg, oxaliplatin 85 mg/m 2, leucovorin 400 mg/m 2, and 5-FU 400 mg/m 2 then 1200 mg/m 2/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m 2 day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m 2. Results: Two hundred forty-seven patients (arm A/arm B 124/123) were enrolled, and 239 were treated (118/121). Twelve-month progression-free survival (PFS) was 45%/32%, objective response rates (ORR) (complete response [CR] + partial response [PR]) were 52%/41%, disease control rates (CR+PR+stable disease [SD]) were 87%/83%, and median overall survival (OS) was 21/19.5 months, respectively. Grade 3-4 neutropenia was higher in arm A (28%/7%), as was grade 3 fatigue (12%/3%), and grade 3 neuropathy (11%/< 1%), whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity, except in arm B patients with KRAS-mutated tumors, which resulted in inferior PFS. Patient satisfaction favored the control (mFOLFOX6-B). Conclusion: FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR, and was not more acceptable to patients. This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC. © 2012 Elsevier Inc. All rights reserved. |
| Keywords: | adult; controlled study; treatment response; aged; aged, 80 and over; disease-free survival; middle aged; patient satisfaction; major clinical study; overall survival; proto-oncogene proteins; fatigue; neutropenia; bevacizumab; fluorouracil; diarrhea; hypertension; anorexia; colorectal cancer; progression free survival; mucosa inflammation; nausea; neuropathy; randomized controlled trial; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; continuous infusion; cetuximab; colorectal neoplasms; antibodies, monoclonal; vein thrombosis; folinic acid; acne; phase 3 clinical trial; ras proteins; kras; oncogene k ras; disease control; oxaliplatin; hand foot syndrome; alopecia; organoplatinum compounds; leucovorin; hematologic disease; antibodies, monoclonal, humanized |
| Journal Title: | Clinical Colorectal Cancer |
| Volume: | 11 |
| Issue: | 2 |
| ISSN: | 1533-0028 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2012-06-01 |
| Start Page: | 101 |
| End Page: | 111 |
| Language: | English |
| DOI: | 10.1016/j.clcc.2011.05.006 |
| PROVIDER: | scopus |
| PUBMED: | 22055112 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 June 2012" - "CODEN: CCCLC" - "Source: Scopus" |
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