Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane
Mené sur 770 patientes atteintes d'un cancer du sein de stade avancé récidivant ou réfractaire, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de la vinflunine à un traitement à base de capécitabine, après l'échec d'un traitement par anthracycline et par taxane
Background : Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting, and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods : Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine (825 mg/m2 twice daily [bid], days 1–14) every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 bid, days 1–14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results : Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone (hazard ratio 0.84, 95% confidence interval [CI] 0.71–0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively). Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio 0.98, 95% CI 0.83–1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions : Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic breast cancer.ClinicalTrials.govNCT01095003
Annals of Oncology 2018