Bladder cancer immunotherapy under way to the new era

Urologists led the way in the use of immunotherapy in cancer, having introduced a groundbreaking study of the tuberculosis vaccine bacille Calmette-Guérin (BCG) in bladder cancer in 1976, said a plenary speaker here today at the American Urological Association (AUA) 2014 Annual Scientific Meeting.

But not much happened in the next 40 years in immunotherapy for bladder cancer, commented Arie Belldegrun, MD, director of the UCLA Institute of Urologic Oncology in Los Angeles. “We are still using immunotherapy [with BCG] for superficial bladder cancers,” he said.

That is all about to change, said Dr. Belldegrun, who gave the inaugural Journal of Urology lecture at the meeting.

Bladder cancer is now the next target in immunotherapy,” he announced.

This will be made clear by oncologists and pharmaceutical company staff at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO), he said.

Immune Checkpoint Blockade Agents

A very small but significant study (n = 31) of an anti–programmed death ligand 1 (PDL1) agent in the second-line treatment of transitional cell carcinoma (TCC) will be presented at the ASCO meeting in June. TCC is the most common bladder cancer in the United States.

The study indicates that in 20 TCC patients who tested positive for anti-PDL1, there was an overall response rate of 50%, with 1 complete response and 9 partial responses.

The median time to response was “only” 43 days, said Dr. Belldegrun, referring to the fact that responses with immunotherapy can be protracted as the immune system revs up. Notably, in this new study, most of the patients (71%) had failed on more than 2 previous treatments.

“This is the beginning of a new era of bladder cancer immunotherapy,” said Dr. Belldegrun.

Other genitourinary cancers, especially renal cell carcinoma, have been the target of immunotherapies that are currently in the spotlight, he said.

For example, the experimental immunotherapy nivolumab (Bristol-Myers Squibb) uses monoclonal antibodies to neutralize the PD-1 protein, an element of tumors that enables them to evade their nemesis — the immune system.

The phase 1 results in renal cell cancer with nivolumab, which were first reported with great acclaim in 2012, were so promising that Bristol-Myers Squibb moved directly into phase 3 trials.

At the upcoming ASCO meeting, further data on nivolumab in metastatic renal cell carcinoma are expected.

Anti-PD-1 therapies belong to a category of immunotherapies known as immune checkpoint blockade agents. Other kindred agents include anti-CTLA-4 antibody therapies, such as ipilimumab (Yervoy, Bristol-Meyers Squibb).

Dr. Belldegrun said that these 2 types of immune checkpoint blockade are poised to enter the record books in oncology. “[They] will be the biggest drugs ever in oncology,” he declared to the AUA audience.

Immunotherapy’s appeal lies in its ability to generate complete and durable responses, he said. Targeted therapies, on the other hand, have fallen short in that regard.

Targeted therapies rose in prominence from 2000 to 2009. There were 7 targeted therapies approved for metastatic renal cell carcinoma in that time, but no complete remissions were recorded. “Multiple drugs, but no cures,” said Dr. Belldegrun.

From Mice to Men

Dr. Belldegrun has seen a tremendous amount of change in immunotherapy research during the course of his career. In 1987, he was a fellow at the National Institutes of Health and was invited to deliver the State of the Art Lecture at the AUA annual meeting. The subject: new approaches to the immunotherapy of cancer. “Most of my talk was mice, not men, unfortunately.”

But things have changed. Urologists need to be part of the “extremely rapidly evolving field” of immunotherapy in cancer to remain the “gatekeepers” of patients with urologic cancers, said Dr. Belldegrun.

Prostate cancer is likely to eventually join the list of cancers treated with immunotherapy, said Micheal Blute, MD, chief of urology at Massachusetts General Hospital in Boston.

“Prostate cancer is responsive to the immune system,” he told Medscape Medical News; however, it was a less obvious target for early testing of immunotherapy strategies such as immune checkpoint blockade. Melanoma and other cancers were more obvious targets because of patients’ shorter life expectancies, said Dr. Blute.

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