NYU Langone Research Leads to Accelerated Approval of Bladder Cancer Immunotherapy Drug

Findings from a clinical trial led by a researcher at NYU Langone’s Perlmutter Cancer Center helped pave the way for the recent, accelerated approval by the US Food and Drug Administration (FDA) of a highly effective immunotherapy as first line treatment for patients with advanced bladder cancer who are not eligible for treatment with standard chemotherapy.

In the clinical trial, the drug, atezolizumab, marketed as Tecentriq and part of a class of drugs known as checkpoint inhibitors, was found to shrink bladder tumors by at least 30 percent and stall new tumor growth in 28 of 119 patients (24 percent). All study participants received the medication as their initial therapy for the disease.

“Atezolizumab is the first therapy ever to be approved for these typically frail patients, who otherwise do not have good treatment options,” says lead investigator and medical oncologist Arjun V. Balar, MD, an assistant professor at NYU Langone and its Perlmutter Cancer Center. “Indeed, it may be the only therapy some patients need.”

Dr. Balar’s research was initially presented at last year’s international conference of the American Society of Clinical Oncology (ASCO) and subsequently published in The Lancet in January of this year.

Balar says that checkpoint inhibitors — several already approved to treat other forms of cancer — are designed to “retrain the immune system” to attack tumor cells by blocking the action of proteins (so-called immune checkpoints) that help cancer cells evade recognition by the immune system. Atezolizumab blocks interaction of the protein PD-L1, or programmed death ligand-1, with the checkpoint protein, PD-1. This “lock and key” connection, Balar says, is critical to the detection of tumor cells by immune system T cells.

For several decades, the “first line” standard of care in bladder cancer, Balar says, has been cisplatin, a chemotherapy drug that kills tumor cells by inducing irreparable damage to their DNA. 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 tolerate this drug because of its toxic side effects on nerve and kidney function, as well as hearing. Moreover, most tumors develop drug resistance to cisplatin and similar chemotherapy medications over time.

In Balar’s study, half of the patients who responded to the new therapy did so within 15 weeks, with the majority remaining on therapy without any detectable signs of cancer growth (at a dose of 1,200 milligrams every three weeks). As part of the study, all 21 patients still in cancer remission continue to be monitored, with some having continued to receive atezolizumab since the study started in May 2014.

Balar says atezolizumab was well tolerated in the study, which was conducted in medical centers across the United States, Canada, and Europe. Patients reported relatively mild instances of fatigue, itchy skin, and diarrhea, which represented far fewer and less-severe side effects than seen with cisplatin or its common alternative, carboplatin, Balar says. (Genetech, the drug’s manufacturer, lists additional side effects as part of its FDA approval, including potential lung, liver, intestinal, glandular, nervous system and eye problems, as well as severe infections and severe infusion reactions.)

An estimated 76,000 Americans will be diagnosed with bladder cancer in 2017. Less than 15 percent survive past five years when the disease is diagnosed in its advanced stages. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

Atezolizumab has previously received FDA approval for patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy, or who have progressed onto an FDA-approved targeted therapy because their cancer has certain gene abnormalities.

Balar is a paid consultant to Genentech, which funded his study and all related clinical trials. Genentech is a subsidiary of Roche. Balar has also received research support from Merck, which is developing a competing immunotherapy to atezolizumab. The terms of these arrangements are being managed in accordance with the policies of NYU Langone.