Immunotherapy in GU Cancers: Combinations Are the Next Step

Immunotherapy is making landmark change in the treatment of patients with genitourinary (GU) cancers, with bladder cancer being the pioneer in the field, having five FDA-approved checkpoint inhibitors. But kidney cancer is not far behind, with a breakthrough therapy designation granted for a Keytruda (pembrolizumab) combination this past January.

Now, researchers are turning to the next set of questions for these agents: How are we going to continue to improve immunotherapy’s efficacy? Will that be in combinations with new or existing drugs?

“In bladder cancer and kidney cancer in particular, we’re seeing a wave of new therapies, such as how to use novel immunotherapies effectively. There are trials now that are addressing combination approaches that I believe will quickly lead to new standards of care, probably in the next one or two years,” Arjun V. Balar. M.D., assistant professor in the Department of Medicine, directory of Genitourinary Medical Oncology Program at NYU Langone’s Perlmutter Cancer Center, said in an interview with OncLive, a sister publication of CURE.

After seeing impressive durable responses with immunotherapy in the second-line setting of bladder cancer, Balar said that the obvious next step is to combine these agents and to look at other immune checkpoints (besides PD-1 and PD-L1), such as CTLA-4.

Ongoing studies are looking at the combination of Yervoy (ipilimumab) with Opdivo (nivolumab), and another randomized phase 3 trial is testing Imfinzi (durvalumab) with tremelimumab (a CTLA-4 plus PD-L1 inhibitor combination).

“It appears that this combination may actually lead to higher response rates, and hopefully these responses are durable,” Balar said.

However, just because immunotherapy is new and exciting in bladder cancer, that does not mean that chemotherapy is going anywhere considering since there is a group of about 5 to 10 percent of patients whose cancer is fast growing and highly symptomatic. These individuals typically do not response well to immunotherapy, and chemotherapy is often the better option.

“There is emerging evidence that certain forms of chemotherapy may combine well with immunotherapy, so we may also see combinatorial approaches. There are certainly phase 3 trials addressing that question, as well,” Balar said.

And while immunotherapy combinations continue to be investigated in the bladder cancer space, Balar predicted that they could make an even bigger splash in kidney cancer, which not only is an immune-responsive tumor, but VEGF-targeting therapy is already standard of care.

Early studies are showing that Inlyta (azitinib) — a VEGF inhibitor – plus Keytruda; Inlyta plus Bavencio (avelumab); and Keytruda plus Lenvima (lenvatinib) are showing response rates upwards of 70 percent, according to Balar.

“This demonstrates that there may be synergy between these agents to generate a more effective antitumor immune response,” he said. “Ultimately, I do believe that these agents will lead to new standards of care in the first-line setting. Ongoing randomized trials hope to demonstrate that this combinatorial approach will lead to durable responses and better overall survival.”