RANGE study of Cyramza(ramucirumab) + docetaxel shows improvement in PFS in patients with urothelial carcinoma.- Eli Lilly.

At the European Society for Medical Oncology (ESMO) 2017 Congress Phase III RANGE data from Eli Lilly and Company were presented in the Presidential Symposium (abstract#: LBA4_PR). These are the first detailed results from the global, randomized, double-blinded, placebo-controlled RANGE study of Cyramza (ramucirumab), in combination with docetaxel, in patients with advanced or metastatic urothelial carcinoma whose disease progressed on or after platinum-based chemotherapy.

The data showed a statistically significant improvement in progression-free survival (PFS) in patients treated with ramucirumab plus docetaxel when compared to those who received placebo plus docetaxel, with a 46 percent prolongation in median PFS. Patients previously treated with a checkpoint inhibitor were allowed to enroll in the RANGE study. PFS is the trial's primary endpoint, and secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR) and patient-reported outcomes (PRO). Patients treated on the ramucirumab-plus-docetaxel arm (n=263) achieved a median PFS of 4.1 months compared to 2.8 months for patients on the placebo-plus-docetaxel arm (n=267). The PFS hazard ratio (HR) was 0.757 (95% CI, 0.607-0.943, p=0.0118), which corresponds to a 24 percent reduction in the rate of disease progression or death. These investigator-assessed PFS results were confirmed by a blinded central radiographic review (HR, 0.672; 95% CI, 0.536-0.842; p=0.0005). In addition, PFS results were consistent across pre-specified subgroups. Importantly, the PFS HR was consistent across three subgroups defined by poor prognostic factors (HR, 0.694-0.764)--patients with ECOG 1 performance status, liver metastases or a short interval of less than or equal to 3 months since prior therapy. The majority of patients (415 of 530) had at least one risk factor--44 percent had two or more.

The safety profile observed in the RANGE study at this data readout was consistent with what has previously been observed for ramucirumab. Grade greater than 3 adverse events were reported at a similar frequency in both arms. The grade greater than 3 adverse events occurring at a rate of five percent or greater, and that were higher on the ramucirumab-plus-docetaxel arm compared to the placebo-plus-docetaxel arm, were neutropenia (15.1% vs. 13.6%), febrile neutropenia (9.7% vs. 6.4%), and hypertension (5.8% vs. 1.9%). Grade greater than 3 cardiovascular events, including arterial or venous thromboembolism and congestive heart failure, were rare in both arms, affecting less than 2% of patients.

Comment: RANGE is the first and only Phase III study of any therapy to show superior PFS over chemotherapy in a post-platinum setting in urothelial cancer.

RANGE OS data are immature and final OS results are currently expected in mid-2018. Investigators, patients and Lilly study personnel involved in patient-level decision-making will remain blinded to patient-treatment assignments until that time.