Combination Improves Responses, Misses Survival Endpoint in Bladder Cancer Trial

The combination use of Cyramza (ramucirumab) plus docetaxel showed improvements in objective response rate (ORR) and a positive trend in overall survival (OS) among patients with advanced bladder cancer, according to additional results from the phase 3 RANGE trial.

OS did not reach statistical significance; however, Lilly, the drug’s manufacturer, previously announced that the trial met its primary endpoint of investigator-assessed progression-free survival (PFS).

Of note, the RANGE study is currently the only one to demonstrate superior PFS compared to chemotherapy in a post-platinum chemotherapy setting in this patient population, and it is the first to show the benefit of targeting angiogenesis in bladder cancer, according to a Lilly press release.

The trial examined the efficacy of the combination in patients with locally advanced or unresectable metastatic bladder cancer who progressed on a platinum-based chemotherapy. The researchers randomized 530 participants to receive either Cyramza plus docetaxel or placebo plus docetaxel.

Most patients had poor prognoses, with 61 percent having two or more adverse prognostic risk factors at baseline, meaning that patients had a condition or health situation that made them more susceptible to cancer recurrence.

Although OS did not meet statistical significance, patients on the trial still experienced benefit from the combination. In fact, there was a 1.3-month improvement in OS and the ORR nearly doubled (24.5 percent vs. 14 percent) compared with placebo.

After a year on the trial, 11.9 percent of patients on the combination regimen were without progression, compared to 4.5 percent for those on docetaxel alone. Even better, complete response rates were three times that of the placebo group (4.2 percent vs. 1.4 percent).

Side effects for each arm of the clinical trial were not drastically different, with 16 percent on the combination regimen experiencing anemia compared with 24 percent on docetaxel alone. That included grade 3 or higher anemia (3 percent and 11 percent, respectively), as well.

The most common reason why patients on the trial stopped treatment was disease progression. This happened in 209 patients in the Cyramza/docetaxel arm and 229 patients in the placebo arm.

"People with advanced urothelial carcinoma who experience disease progression urgently need treatment options that can control the disease — to help stop or slow the cancer from growing and spreading," said Levi Garraway, M.D., Ph.D., senior vice president of global development and medical affairs at Lilly Oncology, said in the release.

"Although this study didn't reach statistical significance for overall survival, we are encouraged by the totality of the RANGE results and look forward to reviewing the data with internal and external experts to determine next steps."