The drug nivolumab, which uses the immune system to attack tumors, is highly effective against advanced bladder cancer, according to clinical trial results from The University of Texas MD Anderson Cancer Center.

The immune checkpoint blockade drug, marketed as Opdivo, lowered tumor burden in 24.4 percent of patients with metastatic bladder cancer, regardless of whether their tumors had a biomarker related to the drug’s target.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO).

“The response rate is better than we’ve seen for other potential second-line treatments and nivolumab is really well-tolerated, which is important because bladder cancer patients are a fragile group after frontline treatment with platinum chemotherapy,"

said Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology at MD Anderson.

Nivolumab prompts an immune system assault on cancer by blocking activation of a protein called PD-1 on T cells, white blood cells that find and attack cells, viruses or bacteria that have specific targets. PD-1 acts as a brake, or checkpoint, to shut down activated T cells.

PD-1 is turned on by a ligand called PD-L1, which is often found on cancer cells and other types of cells.

Side Effects Mild

The presence of PD-L1 on a patient’s tumor has been considered a potential biomarker to guide treatment. The study found no significant difference in response rates between those with little to no PD-L1 on their tumors (26 percent) and those with greater PD-L1 expression (24 percent).

Typical current “first-line” care in bladder cancer is treatment with cisplatin, a drug that kills tumor cells by preventing them from repairing damage to their DNA.

In widespread use since the 1970s, cisplatin extends survival to slightly more than a year, but nearly half of bladder cancer patients, most of whom are elderly with other serious health issues, cannot take it because of its toxic side effects on nerve and kidney function, as well as hearing. Moreover, many patients' cancers develop drug resistance to cisplatin and similar chemotherapy medications over time.

Nivolumab treatment-related side effects included mainly low-grade fatigue, itching, elevated lipase, rash, nausea, joint pain and anemia. Grade 3 or 4 side effects occurred in 20.5 percent of patients. Two patients discontinued therapy because of adverse events related to the drug.

At a median follow up of 213 days, 33.3 percent remained on treatment, and 45.6 percent of patients survived for at least one year, which Sharma noted “is better than anything we’ve seen in the past.”

Overall survival will be analyzed in conjunction with the Phase II portion of this clinical trial, which provides nivolumab or a combination of nivolumab plus the immune checkpoint inhibitor ipilimumab. The trial allows patients to cross over to the combination if nivolumab alone fails.

Initial results from the Phase II portion of the trial will be presented later this year.

Nivolumab and Ipilimumab

Both nivolumab, known as Opdivo, and ipilimumab, known as Yervoy, were developed and marketed by Bristol-Myers Squibb, which funded the clinical trial.

Ipilimumab targets the CTLA-4 checkpoint on T cells and was the first immune checkpoint inhibitor. It was based on the research of Jim Allison, Ph.D., chair of Immunology, executive director of the immunotherapy platform and director of the Parker Institute for Cancer Immunotherapy at MD Anderson.

Ipilimumab was the first drug ever shown to extend the survival of patients with metastatic melanoma. Long-term follow up shows 22 percent of those treated with the drug survive 10 years or longer.

Nivolumab has been approved by the U.S. Food and Drug Administration for advanced melanoma, lung cancer, kidney cancer and Hodgkin lymphoma. The five-year survival rate for those with metastatic melanoma treated with nivolumab is 34 percent. The two-year survival rate of patients treated with both drugs in combination is 69 percent.

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