Guru P. Sonpavde, MD, is the medical director for Genitourinary (GU) Oncology, assistant director of the Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute.

Guru P. Sonpavde, MD, director, Bladder Cancer, and physician, Dana-Farber Cancer Institute, discusses emerging immunotherapy approaches in bladder cancer.

Data from several confirmatory phase III trials with FGFR inhibitors are eagerly anticipated in the bladder cancer space. Furthermore, immunotherapy is under investigation—specifically, looking at PD-1/PD-L1 inhibitors as adjuvant therapy after radical cystectomy to improve cure rates. Perhaps more exciting, says Sonpavde, is neoadjuvant therapy. Phase III trials combining platinum-based chemotherapy plus PD-1/PD-L1 inhibition are ongoing. There are also trials that are being planned in the setting of cisplatin ineligibility in the neoadjuvant space, an area of great unmet need. Right now, the standard of care in this setting is radical cystectomy.

In the neoadjuvant space, several phase II trials evaluating pembrolizumab (Keytruda) or atezolizumab (Tecentriq) alone look promising. Data from those trials showed pathologic complete responses ranging from 30% to 40%, says Sonpavde. Based on these data, phase III trials are being planned to assess the activity of these agents in a larger cohort of patients.

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Dr. Sonpavde on Emerging Immunotherapy Approaches in Bladder Cancer

Guru P. Sonpavde, MD, director, Bladder Cancer, and physician, Dana-Farber Cancer Institute, discusses the biggest challenges in the field of bladder cancer.

Bladder cancer is a heterogeneous disease driven by many pathways and molecules, explains Sonpavde. As such, there is no predominant target. This has been an impediment to improving cure rates. However, these challenges have, in part, been addressed with immunotherapy. Bladder cancer has a high mutation burden, which has enabled advances with this approach.

Combinations of immunotherapy drugs might further enhance the benefit that has been observed to date. There are many ongoing phase I trials looking at these combinations, many of which are open at Dana-Farber Cancer Institute. Sonpavde is hopeful that these combinations will take treatment of the disease to the next level.

Dr. Sonpavde on the Biggest Challenges in Bladder Cancer

Guru P. Sonpavde, MD, director, Bladder Cancer, and physician, Dana-Farber Cancer Institute, discusses therapeutic agents under investigation for patients with PD-L1—low bladder cancer.

There are trials being planned in that patient population, says Sonpavde, and time will tell whether or not the combination of chemotherapy and PD-1/PD-L1 inhibitors will be valuable in this setting. This approach also being looked at in ongoing phase III trials enrolling both cisplatin-eligible and -ineligible patients.

In addition, there is an Intergroup trial for cisplatin-ineligible patients that is comparing the combination of cisplatin and gemcitabine with or without bevacizumab (Avastin) or placebo. Those results are pending, adds Sonpavde. Finally, investigators are also looking into a “kitchen sink” approach in which several agents are being combined together, including durvalumab (Imfinzi) and tremelimumab—a PD-L1 inhibitor and a CLTA-4 inhibitor&mdash;plus platinum-based chemotherapy, compared with chemotherapy, or chemotherapy plus PD-L1 inhibition alone.

Guru P. Sonpavde, MD, director, Bladder Cancer, and physician, Dana-Farber Cancer Institute, discusses therapeutic agents under investigation for patients with PD-L1–low bladder cancer.

Dr. Sonpavde on Agents Under Investigation in PD-L1-Low Bladder Cancer

Guru P. Sonpavde, MD, director, Bladder Cancer, and physician, Dana-Farber Cancer Institute, discusses key data with immunotherapy in metastatic bladder cancer.

Data from several frontline phase III trials are still pending, says Sonpavde. In most of these trials, investigators are combining checkpoint inhibitors with PD-L1 plus CTLA-4 inhibitors. The other strategy being explored is platinum-based chemotherapy plus PD-1/PD-L1 inhibitors. Physicians are still waiting to see what the data will show. Further, investigation into PD-1/PD-L1 inhibitors alone versus chemotherapy in the first-line setting is ongoing, adds Sonpavde.

In terms of PD-L1—low patients, single-agent atezolizumab (Tecentriq) and pembrolizumab (Keytruda) have both been shown to be inferior to chemotherapy with carboplatin and gemcitabine. Therefore, the FDA changed the labels of these agents, only allowing their use in patients who are PD-L1–high and cisplatin-ineligible. For cisplatin-ineligible patients who are PD-L1–low, gemcitabine and carboplatin is the advised frontline therapy.

Guru P. Sonpavde, MD

Articles

Dr. Sonpavde on Emerging Immunotherapy Approaches in Bladder Cancer

Dr. Sonpavde on the Biggest Challenges in Bladder Cancer

Dr. Sonpavde on Agents Under Investigation in PD-L1-Low Bladder Cancer

Dr. Sonpavde on Key Data With Immunotherapy in Metastatic Bladder Cancer