FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial.

Abstract

PURPOSE:

5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab.

PATIENTS AND METHODS:

VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS).

RESULTS:

The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively.

CONCLUSIONS:

First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.

• Authors: Enrique Aranda, Jose Maria Viéitez, Auxiliadora Gómez-España, Silvia Gil Calle, Antonieta Salud-Salvia, Begoña Graña, Pilar Garcia-Alfonso, Fernando Rivera, Guillermo Alfonso Quintero-Aldana, Juan José Reina-Zoilo, Encarnación González-Flores, Mercedes Salgado Fernández, Carmen Guillén-Ponce, Rocio Garcia-Carbonero, María José Safont, Adelaida La Casta Munoa, Beatriz García-Paredes, Rafael López López, Javier Sastre, Eduardo Díaz-Rubio, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD)
• Journal: ESMO open (ESMO Open) Vol. 5 Issue 6 Pg. e000944 (11 2020) ISSN: 2059-7029 [Electronic] England
• PMID: 33148620 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Chemical References

• Organoplatinum Compounds
• Bevacizumab
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Antineoplastic Combined Chemotherapy Protocols
• Bevacizumab (adverse effects)
• Camptothecin (analogs & derivatives)
• Colorectal Neoplasms (drug therapy)
• Fluorouracil
• Humans
• Leucovorin (adverse effects)
• Neoplastic Cells, Circulating
• Organoplatinum Compounds