High Response Rate to Second-Line Combination Antiangiogenic Chemotherapy in Patients with Metastatic Melanoma

Abstract

Objectives: Despite the array of new treatment strategies for the management of metastatic melanoma, the prognosis remains poor when immune checkpoint inhibition and targeted therapy options are exhausted. The antiangiogenic monoclonal antibody bevacizumab has documented its efficacy in the treatment of several solid tumors, when used in combination with standard chemotherapy. Phase II studies and case series have led to the speculation that it may also improve the prognosis when used in stage IV melanoma. Therefore, we investigated the influence of bevacizumab, combined with a platinum-based chemotherapy, in the treatment of melanoma and sought to identify prognostic factors affecting the response. Methods: Eight patients with metastatic melanoma, with documented progress after at least one previous therapy, received bevacizumab (5 mg/kg intravenously every two weeks) in combination with cisplatin (100 mg/m 2 every four weeks) and carboplatin (200 mg/m 2 every four weeks). The therapy was continued until renewed disease progression occurred. The response rate, progression-free and overall survival, and toxicity were evaluated. Results: We observed complete remission in two patients (25%) and partial response in an additional four patients. In one patient, the disease remained stable (total disease control rate of 87.5%). Only one patient (12.5%) had progressive disease. The median progression-free survival was 6 months (range 3 - 37 months). The median overall survival time was 15.5 months (range 6 - 77 months). Every patient experienced at least one adverse event of grade 3 - 4, most commonly bleeding associated with severe thrombocytopenia. Conclusion: Our observations indicate that bevacizumab, in combination with cisplatin and carboplatin, may represent an effective treatment option for patients with metastatic melanoma and disease progression.