Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA Phase 3 Randomized Trial
Mené en Italie sur 3 759 patients atteints d'un cancer du côlon de stade II et III à haut risque de récidive et ayant été réséqué, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans récidive et de la survie globale, et la toxicité d'une chimiothérapie adjuvante de type FOLFOX/CAPOX, dispensée pendant une durée de 3 ou 6 mois (durée médiane de suivi : 7 ans)
Background : Oxaliplatin-based adjuvant chemotherapy is the standard treatment for high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome (in terms of relapse-free survival [RFS]) to a longer duration. This study reports the overall survival (OS) analysis of the phase 3 Three or Six Colon Adjuvant (TOSCA) study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. Material and Methods : TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1:1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary endpoint. Overall survival was a secondary endpoint. Results : From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3 months vs. 6 months arms was 1.13 (95%CI 0.99-1.29, p for non-inferiority=0.380, p for superiority=0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3 months arm. The HR for OS of the 3 months vs. 6 months arms was 1.09 (95%CI 0.93-1.26, p for superiority=0.288). At the last follow-up analysis, the absolute OS difference between arms was less than 1%. Conclusions : The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660.
Annals of Oncology 2020