Randomised phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma
Mené sur 202 patients atteints d'un carcinome hépatocellulaire de stade localement avancé ou métastatique, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'axitinib
Background : Efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1–3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomised, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients and methods : Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomised (2:1) to axitinib/BSC (starting dose 5-mg twice daily) or placebo/BSC. The primary end point was overall survival (OS). Results : The estimated hazard ratio for OS was 0.907 (95% confidence interval [CI] 0.646–1.274; one-sided stratified P=0.287) for axitinib/BSC (n=134) versus placebo/BSC (n=68), with median (95% CI) of 12.7 (10.2–14.9) versus 9.7 (5.9–11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P<0.01) were observed in secondary efficacy end point analyses (progression-free survival [PFS], time to tumour progression [TTP], and clinical benefit rate [CBR]), and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhea (54%), hypertension (54%), and decreased appetite (47%). Baseline, serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. Conclusions : Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. Trial Registration : ClinicalTrials.gov, NCT01210495