295 Background: Patients (pts) with metastatic urothelial carcinoma (UC) progressing after first-line chemotherapy have limited treatment options. Ramucirumab (Ram), a human VEGFR2-targeted mAb, has demonstrated clinical activity in several solid tumors. Preclinical testing supports a role for Ram-taxane combinations in UC. Study JCDC is an open-label, multicenter, randomized phase 2 study of docetaxel (Doc) alone or combined with Ram or icrucumab (Icr) in locally advanced or metastatic platinum-resistant UC. We report on a planned interim analysis for Doc + Ram vs Doc; Icr results will be reported later. Methods: Eligible pts with advanced UC and ECOG PS 0-1 who relapsed ≤ 1 year from a platinum-regimen were randomized to receive Doc 75 mg/m2IV alone or with Ram 10mg/kg IV on Day 1 of repeating 21-day cycles. A sample size of 46 pts per arm enabled 71% power to demonstrate statistical significance of 4.5 mo (Doc + Ram) vs 3 mo (Doc) at a 1-sided α= 0.1. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed PFS with RECIST v1.1, analyzed by K-M methods. A planned interim analysis was performed after 75% of the PFS events. Results: 44 pts received Doc and 46 received Doc + Ram. Study arms were well matched with a mean age of 67 yr (29-84), and a 4:1 male to female ratio. 58.7% (Doc + Ram) vs 61.4% (Doc) had ECOG PS 1. 58.7% (Doc + Ram) vs 52.3% (Doc) had visceral metastases. Doc + Ram reduced the risk of disease progression, stratified HR = 0.388; 95% CI: 0.222, 0.677; log-rank p = 0.0005, improving median PFS (5.1 vs 2.4 mo). The ORR for Doc + Ram was 19.6 vs 4.5% for Doc (p= 0.0502), and the disease control rate was 67.4 vs 43.2%. OS maturity is pending. The most common adverse events in the Doc + Ram arm (all grades) were fatigue (80.4% Doc + Ram v 75.0% Doc), decreased appetite (54.3 v 43.2%), nausea (54.3 v 25.0%), and neuropathy (50.0 v 38.6%). Grade (G) ≥3 febrile neutropenia (19.6 v 11.4%), pneumonia (13 v 9.1%), hypertension (4.3 v 0%) were higher with Doc + Ram. One G3 hematuria was observed in each arm. Conclusions: Results support a statistically significant improvement in PFS for Doc + Ram in second-line UC. Final results are expected in 2015. Clinical trial information: NCT01282463.
Phase 2 study of pembrolizumab alone or combined with acalabrutinib in platinum-refractory metastatic urothelial carcinoma (mUC)