IMMUNOTHERAPY FOR BLADDER CANCER

The race is on to establish new immunotherapy agents to treat bladder cancer. Such an advance would be the first since the historic bacille Calmette-Guérin (BCG) immunotherapy showed benefit in this disease 40 years ago.

One contender is the investigational programmed cell death (PD) inhibitor atezolizumab (Roche/Genentech), which has shown promise in a phase 2 trial of bladder cancer and is now being investigated in phase 3 trials.

Atezolizumab will face "strong competition" in the bladder cancer market from the two PD inhibitors that are already on approved for other indications: nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck).

Both of these drugs are now being investigated in bladder cancer, but Roche currently has a broader development program for atezolizumab in bladder cancer than its competitors, according to a report by Cai Xuan, PhD, an analyst from the GlobalData research firm.

One of the phase 3 trials of atezolizumab, known as IMvigor 211, is comparing the agent with standard-of-care chemotherapy in patients with relapsed urothelial bladder cancer. Another phase 3 trial, known as IMvigor 010, is evaluating atezolizumab as an adjuvant therapy in patients with early-stage, PD-L1-positive, muscle-invasive bladder cancer who are at risk for recurrence.

"The potential to expand into multiple indications will make this drug an important player in a wave of long-awaited bladder cancer treatment innovation," Dr Xuan said.

Details of Atezolizumab Activity

The phase 2 study of atezolizumab — IMvigor 210 study — was successful, having met its primary end point of objective response rate, Roche announced earlier this month.

In the open-label, multicenter, single-group study, patients with locally advanced or metastatic urothelial bladder cancer who had progressed on initial treatment (second-line or later) were treated with intravenous atezolizumab 1200 mg on day 1 of 21-day cycles until the loss of clinical benefit.

Responses to the agent were better in patients with higher levels of PD-L1 expression.

"We plan to present results at an upcoming medical meeting, and will discuss the next steps with health authorities to bring a new treatment option to patients as soon as possible." said Sandra Horning, MD, chief medical officer of Roche.

The company is investigating the drug in several other types of cancer, and has ongoing or planned phase 3 trials in lung, kidney, and breast cancer, and two in bladder cancer.

Earlier phase 1a results with atezolizumab were "encouraging," Dr Xuan states in her GlobalData report. "The drug caused tumors to shrink in 50% of patients previously treated for PD-L1-positive, metastatic urothelial bladder cancer," she explains.

Last year, the US Food and Drug Administration granted breakthrough therapy designation for atezolizumab in patients whose metastatic bladder cancer expresses PD-L1.

One of First Targets of Immunotherapy

Bladder cancer was the one of the first targets of immunotherapy in oncology.

In a groundbreaking study, the BCG vaccine for tuberculosis was shown to be beneficial in patients with bladder cancer (J Urol. 1976;116:180-183). But not much happened in the next 40 years in immunotherapy for bladder cancer, Arie Belldegrun, MD, director of the UCLA Institute of Urologic Oncology in Los Angeles, explained at the 2014 American Urological Association Annual Scientific Meeting, as reported by Medscape Medical News.

"We are still using immunotherapy [with BCG] for superficial bladder cancers," he said at the time.