| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer: The UNICANCER PRODIGE18 Randomized Clinical Trial |
| Creator | Bennouna et al. |
| Author | Jaafar Bennouna |
| Author | Sandrine Hiret |
| Author | Aurelie Bertaut |
| Author | Olivier Bouché |
| Author | Christian Borel |
| Author | Thierry Conroy |
| Author | François Ghiringhelli |
| Author | Gaëtan des Guetz |
| Author | Jean-François Seitz |
| Author | Pascal Artru |
| Author | Mohamed Hebbar |
| Author | Trevor Stanbury |
| Author | Marc G. Denis |
| Author | Antoine Adenis |
| Author | Christophe Borg |
| Abstract | Importance: Second-line treatment with chemotherapy plus bevacizumab or cetuximab is a valid option for metastatic colorectal cancer. Objective: To evaluate the progression-free survival (PFS) rate at 4 months with chemotherapy plus bevacizumab vs cetuximab for patients with progression of metastatic colorectal cancer after bevacizumab plus chemotherapy. Design, Setting, and Participants: A prospective, open-label, multicenter, randomized phase 2 trial was conducted from December 14, 2010, to May 5, 2015. The main eligibility criterion was disease progression after bevacizumab plus fluorouracil with irinotecan or oxaliplatin in patients with wild-type KRAS exon 2 metastatic colorectal cancer. All analyses were performed on the modified intent-to-treat population. Interventions: Patients were randomized to arm A (FOLFIRI [fluorouracil and folinic acid combined with irinotecan] or modified FOLFOX6 [fluorouracil and folinic acid combined with oxaliplatin] plus bevacizumab) or arm B (FOLFIRI or modified FOLFOX6 plus cetuximab); the second-line chemotherapy regimen was chosen according to first-line treatment (crossover). Main Outcomes and Measures: The primary end point was the 4-month PFS rate. Secondary end points included safety, objective response rate, overall survival, and PFS. Results: A total of 132 patients (47 women and 85 men; median age, 63.0 years [range, 33.0-84.0 years]; 74 patients with an Eastern Cooperative Oncology Group performance status of 0, 54 patients with a performance status of 1, and 4 patients with unknown performance status) were included at 25 sites. The 4-month PFS rate was 80.3% (95 CI%, 68.0%-88.3%) in arm A and 66.7% (95% CI, 53.6%-76.8%) in arm B. The median PFS was 7.1 months (95% CI, 5.7-8.2 months) in arm A and 5.6 months (95% CI, 4.2-6.5 months) in arm B (hazard ratio, 0.71; 95% CI, 0.50-1.02; P?=?.06), and the median overall survival was 15.8 months (95% CI, 9.5-22.3 months) in arm A and 10.4 months (95% CI, 7.0-16.2 months) in arm B (hazard ratio, 0.69; 95% CI, 0.46-1.04; P?=?.08). A central analysis of KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), and BRAF (V600) was performed for 95 tumor samples. Eighty-one patients had wild-type KRAS and wild-type NRAS tumors. Conclusions and Relevance: The results of the PRODIGE18 (Partenariat de Recherche en Oncologie DIGEstive) study showed a nonsignificant difference but favored continuation of bevacizumab with chemotherapy crossover for patients with wild-type RAS metastatic colorectal cancer that progressed with first-line bevacizumab plus chemotherapy. Trial Registration: ClinicalTrials.gov identifier: NCT01442649 and clinicaltrialsregister.eu identifier: EUDRACT 2009-012942-22. |
| Publication | JAMA oncology |
| Date | Oct 25, 2018 |
| Journal Abbr | JAMA Oncol |
| Language | eng |
| DOI | 10.1001/jamaoncol.2018.4465 |
| ISSN | 2374-2445 |
| Short Title | Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer |
| Library Catalog | PubMed |
| Extra | PMID: 30422156 |
| Tags | Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Biomarkers, Tumor, Cetuximab, clinic, Colorectal Neoplasms, Disease Progression, Female, Fluorouracil, Humans, Leucovorin, Male, Middle Aged, Neoplasm Metastasis, Progression-Free Survival, Prospective Studies, Proto-Oncogene Proteins p21(ras), Time Factors |
| Date Added | 2018/11/16 - 10:55:29 |
| Date Modified | 2020/01/28 - 09:49:58 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
