Induction chemotherapy (CT) with FOLFIRINOX or FOLFOX/FOLFIRI, plus cetuximab (CET) or bevacizumab (BEV) (by RAS status), in patients (pts) with primarily unresectable colorectal liver metastases (CRLM): Results of the randomized UNICANCER PRODIGE 14-ACCORD 21 (METHEP-2) trial.
2018; Lippincott Williams & Wilkins; Volume: 36; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2018.36.15_suppl.3535
ISSN1527-7755
AutoresMarc Ychou, Michel Rivoire, Simon Thézenas, Rosine Guimbaud, François Ghiringhelli, Anne Mercier Blas, Laurent Mineur, Éric François, Faïza Khemissa, Marion Chauvenet, Y. Bécouarn, Philippe Houyau, Thomas Aparicio, Marie Pierre Galais, Franck Audemar, Éric Assenat, Antoine Adenis, Claire Jouffroy-Zeller, René Adam, Olivier Bouché,
Tópico(s)MRI in cancer diagnosis
Resumo3535 Background: pts with unresectable CRLM who respond to induction CT allowing curative-intent liver surgery have longer overall survival (OS) than pts who do not. Triplet (3-) or doublets (2-) CT, combined with CET or BEV, are often used in this setting. However, the best CT regimen remains to be determined. Methods: METHEP2 assessed whether 3-CT (FOLFIRINOX) compared to 2-CT (FOLFOX or FOLFIRI), combined with CET or BEV (by KRAS/RAS status), would increase R0/R1 liver-resection rate in pts with initially unresectable CRLM. Randomization was stratified by KRAS (amended to RAS) status, meta- vs. synchronous CRLM, and reason for non-resectability (technical vs. oncological). It was designed to demonstrate a 20% increase in the R0/R1 liver-resection rate (2-CT arm, 50% vs. 3-CT arm, 70%; bilateral α-test, 5%; β, 10%). Results: 256 pts were included, 126 in the 2-CT arm (FOLFIRI, 56; FOLFOX4, 70) and 130 in the 3-CT arm. KRAS and RAS were mutated in 91 pts (35.5%) and in 109 pts (42.6%), respectively. After a median follow-up of 45.6 months (mo), R0/R1 liver resection was achieved in 74/130 pts (56.9%; 95%CI, 48-66) in the 3-CT arm vs. 61/126 pts (48.4%; 95%CI, 39-57) in the 2-CT arm (p = 0.17). The odds for R0/R1 resection were higher in the 3-CT than in the 2-CT arm (OR, 1.8; 95%CI, 1.1-2.7; p < 0.02) when using a logistic regression model adjusted on stratification factors. Median OS was 42.9 mo in the 3-CT arm vs. 37.6 mo in the 2-CT arm (HR = 0.80; 95%CI, 0.56-1.16). Efficacy by targeted agent was as follows: R0/R1 resection 86/153 (56.2%; 95%CI, 48-64) and 49/103 (47.6%; 95%CI, 38-58), objective response: 120/153 (78.4%; 95%CI, 71-85) and 58/103 (56.3%; 95CI, 46-66), mPFS: 12.8 mo (95%CI, 11.6-13.1) and 10.7 mo (95%CI, 9.7-13.1), OS: 43.6 mo (95%CI, 40.0-51.8) and 34.2 mo (95%CI, 27.8-40.4), for CET- and BEV-treated pts, respectively. Conclusions: Despite not reaching our primary objective, FOLFIRINOX tends to be superior to FOLFIRI/FOLFOX, combined with CET or BEV, in terms of R0/R1 liver-resection rate in pts with initially unresectable CRLM. Clinical trial information: NCT01442935.
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