Triple combination of bevacizumab, gemcitabine and platinum salt in metastatic collecting duct carcinoma

Background: Collecting duct carcinoma (CDC) is a rare and aggressive subtype of kidney cancer that responds to platinum-based chemotherapy. Recent phase II trials have established enhanced antitumor activity on combining bevacizumab with chemotherapy in patients with metastatic urothelial carcinoma, a tumor that shares many features with CDC. Our aim was to investigate whether combining bevacizumab with platinum-based chemotherapy might not also show promise in metastatic CDC (mCDC) patients. Patients and methods: Five previously untreated patients diagnosed with mCDC received bevacizumab (15 mg/kg) in combination with gemcitabine (1250 mg/m2, D1-D8) and platinum salt (cisplatin 80 mg/m2 or carboplatin AUC 5 mg/ml/min) every 3 weeks for up to six cycles. This was followed by bevacizumab maintenance therapy (15 mg/kg). Results: All five patients (median age, 62 years; range 45-66 years) had an Eastern Cooperative Oncology Group PS of 0-1. They received the triple-drug combination for a median of four cycles (range, 2-6) and bevacizumab maintenance therapy for a median of three cycles (range, 0-17). There were three cases of partial response, one case of stable disease (20 months) and one case of complete remission after surgery of the only metastatic site. Median progression-free survival (PFS) was 15.1 months [95% confidence interval (CI) 5.6-20.4]. Median overall survival (OS) was 27.8 months(95% CI 12.4-unreached). Grades 3 or 4 adverse events were pulmonary embolism (n = 2), neutropenia (n = 2), thrombopenia (n = 1), asthenia (n = 1) and hypertension (n = 1). Conclusions: The addition of bevacizumab to platinum-based chemotherapy resulted in a longer PFS and longer OS than recorded in an earlier clinical trial of platinum-based chemotherapy alone. The triple combination was manageable. The French Collaborative Group (Groupe d'Etudes des Tumeurs Uro-Génitales) is planning a prospective multicenter phase II clinical trial of the triple combination in mCDC patients. Clinical Trial:: BEVABEL/MO28644 (EudraCT: 2013-001179-19).