Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial.

Abstract

BACKGROUND:

Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting.

METHODS:

PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx.

RESULTS:

Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx.

CONCLUSION:

We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.

• Authors: Marc Ychou, Michel Rivoire, Simon Thezenas, Rosine Guimbaud, Francois Ghiringhelli, Anne Mercier-Blas, Laurent Mineur, Eric Francois, Faiza Khemissa, Marion Chauvenet, Reza Kianmanesh, Marianne Fonck, Philippe Houyau, Thomas Aparicio, Marie-Pierre Galais, Franck Audemar, Eric Assenat, Evelyne Lopez-Crapez, Claire Jouffroy, Antoine Adenis, René Adam, Olivier Bouché
• Journal: British journal of cancer (Br J Cancer) Vol. 126 Issue 9 Pg. 1264-1270 (05 2022) ISSN: 1532-1827 [Electronic] England
• PMID: 34992255 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Bevacizumab
• Cetuximab
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (therapeutic use)
• Camptothecin (therapeutic use)
• Cetuximab (therapeutic use)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Liver Neoplasms (drug therapy, genetics, secondary)
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy)