Arjun V. Balar, MD
Over the last few years, immunotherapy has taken center stage in the landscape of bladder cancer, with the approval of 5 PD-1/PD-L1 agents: atezolizumab (Tecentriq) and pembrolizumab (Keytruda)—both as first- and second-line therapies—and avelumab (Bavencio), durvalumab (Imfinzi), and nivolumab (Opdivo) in the second-line setting. Next steps in this field, experts have noted, are to study these agents in combination with other novel or existing therapies.
Additionally, kidney cancer has also seen an emergence of immunotherapy approaches, especially as combinations. For example, a breakthrough therapy designation was granted by the FDA in January 2018 to the combination of pembrolizumab and the VEGF/FGF inhibitor lenvatinib (Lenvima) for the treatment of patients with advanced and/or metastatic disease. Moreover, in December 2017, the FDA granted avelumab plus the VEGF inhibitor axitinib (Inlyta) a breakthrough therapy designation in treatment-naïve patients with advanced disease.
“There are many advances taking place in the management of genitourinary cancers,” said Arjun V. Balar, MD. “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 1 or 2 years. It’s critical to follow along with these studies to maintain an updated standard of care.”
In an interview during the 2018 OncLive® State of the Science SummitTM on Genitourinary (GU) Cancers, Balar, assistant professor, Department of Medicine, director, Genitourinary Medical Oncology Program, NYU Langone’s Perlmutter Cancer Center, and chair of the meeting, discussed the landscape of current and future standards of care for immunotherapy in bladder and kidney cancer.
OncLive: What is the state of immunotherapy in GU cancers?
Balar: At the State of the Science SummitTM on GU Cancers, we spoke about advances in the management of GU cancers and, specifically, my area of focus on the talk was a focus on patients who were treated with metastatic kidney and bladder cancers. In advanced bladder cancer, we have seen a wave of new therapies being approved. These include agents targeting the PD-1 pathway. We have 5 agents approved in the second-line setting, and we have 2 agents approved in the first-line setting. This has been a very active year in terms of drug development. I’ve covered all of the data that supported the approvals of these agents.
Then, I turned my attention toward the management of kidney cancers, where we have also seen a great deal of activity in terms of new therapies. I reviewed the data with respect to immunotherapy in the second-line setting, as well as emerging agents that include combinations in the first-line setting.
Can you expand on some of these new therapies?
Immune checkpoint inhibitors, in particular PD-1 pathway inhibitors in bladder cancer, have led to rapid and durable responses in the second-line setting. What we have seen, as a summary of the phase II and phase III trials, is response rates between 15% and 20%. In the second-line setting, these responses have been durable. The longest-term follow-up shows that some of these responses are going into multiple years—2 and 3 years after starting treatment, which is quite promising.
Even more [impressive] are the data that we’re seeing in the first-line setting for patients with cisplatin-ineligible disease. Two agents are currently approved [in that setting]. The median survival for 1 of the agents has been reported at 15.9 months. This appears to be much better than what we would typically expect for this patient population, which is approximately 9 months when they are treated with carboplatin-based therapy.
Will we start looking at more combination regimens of immunotherapy plus targeted therapy in bladder cancer?
In bladder cancer, the next step is obviously to combine agents. One of the interesting things to look at is other immune checkpoints, such as CTLA-4. We are seeing ongoing studies that are looking at combining ipilimumab (Yervoy) with nivolumab. Also, another randomized phase III trial is testing durvalumab with tremelimumab, which is a CTLA-4 antibody and PD-L1 combination. It appears that this combination may actually lead to higher response rates, and hopefully these responses are durable.