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Immunotherapies move toward FDA approval for urothelial Ca


Two late-stage immunotherapy drugs for the treatment of urothelial carcinoma reach regulatory, research milestones.

Two investigational immunotherapy drugs, pembrolizumab (Keytruda) and nivolumab (Opdivo), are making progress toward FDA approval for treatment of urothelial carcinoma.

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Last month, Merck announced that the anti-PD-1 (programmed cell death protein 1) therapy, pembrolizumab, met the primary endpoint of overall survival in a phase III trial investigating its use in patients with previously treated advanced urothelial cancer. The drug was superior compared to chemotherapy, and an independent data monitoring committee recommended the trial be halted because it met its primary endpoint.

In related news, Bristol-Myers Squibb announced that nivolumab, also a PD-1 inhibitor, has been granted priority review by the FDA for second-line therapy in advanced urothelial carcinoma. The company hopes to expand the treatment’s use to patients with locally advanced unresectable or metastatic urothelial carcinoma that has progressed on or after platinum-containing therapy.

Immune checkpoint inhibitors can be considered a game-changer in urothelial bladder cancer, according to Urology Times Editorial Council member Leonard G. Gomella, MD, of Thomas Jefferson University, Philadelphia.

“Strong basic science and clinical evidence exist for the use of immunotherapy in the treatment of all stages of urothelial carcinoma. Urothelial cancers have been shown to express compounds that suppress the immune system. New immunotherapies directed against urothelial carcinoma include ‘checkpoint inhibitors’ that can reverse the tumor-related immune suppression and allow more effective immunotherapy-mediated tumor killing,” said Dr. Gomella, who is also the current president of the Society of Urologic Oncology.

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The PD-L1 protein is found on certain tumor cells and binds to a receptor, PD-1, on immune cells, which results in immune suppression, Dr. Gomella explains.

“The use of monoclonal antibody checkpoint inhibitors (anti PD-1 and anti PD-L1) has demonstrated significant antitumor activity in patients with metastatic urothelial carcinoma who have failed cisplatin-based therapy, the current standard for advanced urothelial carcinoma,” he said.

Another PD-L1 inhibitor, atezolizumab (Tecentriq), was approved in May 2016 as second-line therapy for urothelial carcinoma.

Next: More about pembrolizumab, nivolumab


Merck announced in October that pembrolizumab is the first immunotherapy to show improved overall survival compared with chemotherapy in urothelial cancer. Researchers conducting the KEYNOTE-045 phase III trial on the drug evaluated pembrolizumab monotherapy compared with chemotherapy (paclitaxel [Abraxane], docetaxel [Taxotere], vinflunine [Javlor]) in the treatment of patients with metastatic, locally advanced, or unresectable urothelial cancer that had recurred or progressed following platinum-based chemotherapy. In that randomized trial, 542 patients received pembrolizumab (200 mg every 3 weeks) or investigator choice of paclitaxel (175 mg/m2 every 3 weeks), docetaxel (75 mg/m2 every 3 weeks), or vinflunine (320 mg/m2 every 3 weeks), according to a press release from the European Society for Medical Oncology.

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Bristol-Myers Squibb’s FDA priority review submission was based on results from the phase II CheckMate –275 study, evaluating nivolumab in patients with previously treated platinum-refractory metastatic urothelial carcinoma. The single-arm clinical trial looked at the drug’s safety and efficacy in 270 patients with metastatic or unresectable urothelial carcinoma that has progressed or recurred following treatment with a platinum-based agent in the metastatic setting or within 1 year after neoadjuvant/adjuvant platinum therapy.

The FDA had granted nivolumab breakthrough therapy designation for metastatic urothelial carcinoma in June 2016. The FDA action date on this new announcement is March 2, 2017, according to a Bristol-Myers Squibb press release.

“Studies are underway to use these checkpoint inhibitors up front and in combination with BCG [bacillus Calmette-Guérin] earlier in the course of the disease. In the future, these agents have the potential to replace cisplatin-based regimens as primary therapy for advanced disease. Strategies, such as staining for PD-L1 and PD-1, may optimize which patients will derive the most benefit from checkpoint inhibition,” Dr. Gomella said.

Dr. Gomella is a consultant for Merck.

More from Urology Times:

What anti-PD-L1 immunotherapy approval means for urology

A new castration-resistant prostate cancer entity?

Clinical pathways: A roadmap to medical success

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