Two Large Trials Investigate Combination Immunotherapy in Bladder Cancer

With five immunotherapy drugs approved in the bladder cancer space, the next question researchers find themselves asking is whether these drugs would work better alone or as part of a combination for patients with metastatic disease. Two clinical trials — Imvigor130 and CheckMate-901 – may soon provide that answer.

“The takeaway from the first-line trials in metastatic bladder cancer is the questions that are being asked right now are very practical, straightforward questions, but they are questions that can only be answered in the context of a large, randomized clinical trial,” Matthew Galsky, M.D., said in an interview with OncLive, a sister publication of CURE.

“We can speculate about that all we want, but the only way to determine those answers definitively is through prospective clinical trials,” he added.

IMvigor130 is a randomized phase 3 study designed to evaluate Tecentriq (atezolizumab) alone and in combination with a platinum-based chemotherapy, compared with chemotherapy plus a placebo, in patients with locally advanced or metastatic bladder cancer in the first line setting.

CheckMate-901 is a randomized, open-label phase 3 trial designed to compare Opdivo (nivolumab) plus Yervoy (ipilimumab) and Opdivo plus standard of care chemotherapy versus standard of care chemotherapy alone in patients with unresectable or metastatic bladder cancer who have had no prior treatments.

“Now, five PD-1/PD-L1 inhibitors are approved for the second-line treatment of patients with metastatic bladder cancer, progressing despite first-line chemotherapy,” explained Galsky, who is professor of medicine, hematology and medical oncology at Mount Sinai Hospital. Therefore, in CheckMate-901, the primary endpoint of the study is based on the population of patients who are not eligible for treatment with cisplatin.

With this, many question whether these drugs should be introduced earlier in the course of treatment. “Since they seem not to be cross-resistant with chemotherapy and have nonoverlapping toxicity profiles, should we combine them with chemotherapy?” Galsky questioned.

He explained that traditionally the frontline treatment for patients with metastatic bladder cancer is chemotherapy, either cisplatin- or carboplatin-based. About 30 to 50 percent of these patients respond to therapy but, unfortunately, the majority experience disease progression.

However, chemotherapy’s role is likely to shift with the addition of immunotherapy agents.

“I see a potential scenario where chemotherapy plays a lesser role in the treatment of patients with bladder cancer, but I don’t suspect that it is going away,” Galsky said. “I suspect that in at least some patients, the combination of chemotherapy and immune checkpoint blockade — if the clinical trials will read out like we think they will – will be standard of care.”

This potential is just one of the major advances being made in the field of bladder cancer.

“Clearly, there is momentum in terms of drug development in this disease,” he added. “That momentum has almost certainly translated into patient benefit, and the hope is that this momentum will continue with additional therapies that are not cross-resistant to ultimately offer our patients even longer and better survival.”