Aflibercept (VEGF Trap) in Inoperable Stage III or Stage IV Melanoma of Cutaneous or Uveal Origin
Mené sur 41 patients atteints d'un mélanome métastatique d'origine cutanée ou uvéale, cet essai de phase II évalue l'aflibercept, un inhibiteur de l'angiogenèse et du récepteur BEGF
Purpose: Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor with potent preclinical antitumor activity in melanoma. We conducted a multicenter phase II study in patients with inoperable stage III or IV melanoma and no prior chemotherapy. Experimental Design: A 2-stage design was adopted to evaluate 4-month PFS rate(PFSR) and response rate. Aflibercept was given at 4 mg/kg IV every 2weeks. Response was assessed every 8weeks. First stage accrual of 21patients was specified, and with an adequate 4-month PFSR accrual continued to a total of 41. Results: Forty-one patients of age 23-84(median 57) were enrolled. Thirty-nine had AJCC stage IV(5M1a, 7M1b, 27M1c) and 2 had inoperable stage IIIC(N3). ECOG PS was 0 (27patients), or 1(14patients). Ten patients had primary uveal melanoma, 28 cutaneous and 3 unknown primaries. A median of 7cycles were initiated (range 1-56). Grade 3/4 toxicities included hypertension in 9 patients(22%) and proteinuria in 6(15%). Among 40 patients evaluable for efficacy (those who initiated aflibercept), 3(7.5%) had a confirmed PR, and twenty had PFS of ≥4months. The predicted one year survival rate derived from the Korn meta-analysis model is 36%(N=39), while we observed a corresponding 56.4% survival at one year (95%CI43%-74%), p{less than}0.005. Median OS in this trial is 16.3 months, (95% CI 9.2mos-not reached). We observed a significant association between severity of hypertension following aflibercept and survival improvement. Conclusions: Aflibercept demonstrated promising activity in patients with metastatic melanoma of cutaneous or uveal origin. Further evaluation of aflibercept as a single agent and in combination is warranted.