TAS-102 plus bevacizumab: a new standard for metastatic colorectal cancer?
Mené au Danemark sur 93 patients atteints d'un cancer colorectal métastatique chimioréfractaire (durée médiane de suivi : 10 mois), cet essai randomisé multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement par TAS-102 seul ou en combinaison avec le bévacizumab
For patients with surgically unresectable metastatic colorectal cancer, a continuum of care is offered to improve their overall outcome. Few treatment options exist apart from oxaliplatin and irinotecan-based therapies; even fewer exist for patients with RAS mutations, who account for 30–60% of all patients with metastatic colorectal cancer. When the oral agent, TAS-102, was approved by the US Food and Drug Administration in 2017, it offered another potential option for patients with surgically unresectable, metastatic colorectal cancer. Often incorrectly touted as a modified oral fluorouracil, TAS-102 differentiates itself by being comprised of two components: trifluridine, a nucleoside analogue, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor, combined in a 1·0:0·5 ratio. Tipiracil prevents rapid degradation of trifluridine resulting in increased bioavailability. The phase 3 RECOURSE trial 3 randomly assigned patients (2:1) with metastatic colorectal cancer (n=800) to receive either TAS-102 (35 mg/m 2, days 1–5 and 8–12) or placebo. The primary endpoint of overall survival was met, with longer median overall survival in the TAS-102 group (7·1 months vs 5·3 months in the placebo group) with a hazard ratio (HR) of 0·68 (95% CI 0·58–0·81; p<0·001). Progression-free survival was also longer in the TAS-102 group than in the placebo group (2·0 months vs 1·7 months [0·48, 0·41–0·57; p<0·001]); and a response was achieved in 1·6% of patients in the TAS-102 group versus 0·4% in the placebo group (p=0·29). The duration of response with TAS-102 ranged from 0·1–78 weeks. The most common adverse event in the TAS-102 group was grade 3 or 4 neutropenia occurring, in 35·9% of patients.
The Lancet Oncology , commentaire, 2019