A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC).

Abstract

307 Background: Translational studies have shown that shed MET levels in serum and urine of pts with UC correlate with stage and visceral metastases and that cabozantinib reverses HGF-driven UC cell growth and invasion. These data support the evaluation of cabozantinib in pts with mUC. Methods: In this phase II study, pts receive cabozantinib 60 mg daily in 28-day cycles. There are 3 study cohorts (1) mUC, (2) bone only mUC (3) metastatic rare bladder histology. The primary objective is to determine the response rate (RR) by RECIST. Response is assessed every 2 cycles. Tissue, blood, and urine were collected on all pts to test for MET/HGF and immune subsets. Results: 26 out of 55 pts have enrolled (19 M, 7 F): median age 62 (42-82) and median KPS of 80%. Primary sites include bladder (77%) and upper tract UC (23%). Prior therapy includes 30% pts with 1 regimen, 39% with 2, 15% with 3, 8% with 4 and 8% with 6. 81% of pts had visceral metastases (lung, liver and bone) and 19% lymph node only metastases. 23 pts (19 in cohort 1, 3 in cohort 2 and 1 in cohort 3) were evaluable for response after completing at least 4 weeks of therapy. In cohort 1, 2 pts achieved PR (1 remained on study for 10 months and 1 remains on study after >12 months of therapy); 7 pts had SD for at least 16 weeks (1 remained on study for 11 months); 10 had PD; 1 is too early to assess for response; 1 was removed before restaging for toxicity and 1 was removed for not meeting eligibility. The objective RR is 11% and SD 37% for a clinical benefit of 48%. In cohort 2, 1 of 3 pts had a near resolution of bone lesions on NaF PET/CT for 11 months. In cohort 3, only pt enrolled (squamous cell carcinoma of the bladder) achieved SD for 16 weeks. Mixed responses with regression of lung, bone or lymph nodes were observed in 30% of pts with PD. Grade 3/4 toxicities included: fatigue (8%), hyponatremia (8%), hypophosphatemia (8%) diarrhea (4%), thromboembolism (4%), transaminitis (4%), hypothyroidism (4%), thrombocytopenia (4%), dysphonia (4%), hypomagnesemia (4%), creatinine increase (4%) and proteinuria (4%). Conclusions: Cabozantinib has clinical activity in pts with relapsed or refractory mUC with manageable toxicities. Further studies are underway to correlate response to therapy with MET expression. Clinical trial information: NCT01688999.