Bavencio Shows Benefit as 1st-line Maintenance Therapy for Bladder Cancer in Phase 3 Trial

Bavencio Shows Benefit as 1st-line Maintenance Therapy for Bladder Cancer in Phase 3 Trial

First-line maintenance therapy with Bavencio (avelumab) significantly delays disease progression or death in people with inoperable, locally advanced or metastatic urothelial carcinoma, a common type of bladder cancer, according to interim data from a Phase 3 trial.

This survival benefit was observed regardless of the levels of the PD-L1 protein in cancer cells (the therapy’s target), highlighting that Bavencio may be effective in treating advanced bladder cancer patients who achieve at least disease stabilization after first-line platinum-based chemotherapy.

“Bavencio is the first immunotherapy to demonstrate a statistically significant improvement in overall survival in a Phase 3 clinical trial in the first-line setting for patients with locally advanced or metastatic urothelial carcinoma,” Chris Boshoff, MD, PhD, Pfizer’s chief development officer for oncology, said in a press release.

These interim findings, “Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis,” were recently presented virtually at the 2020 American Society of Clinical Oncology (ASCO) annual meeting.

Bavencio is an immune checkpoint inhibitor marketed by Pfizer and EMD Serono (known as Merck KGaA outside North America). It is designed to boost anti-tumor responses by blocking the binding of PD-L1 in cancer cells to the PD-1 protein in immune T-cells, a mechanism often used by tumors to evade immune attacks.

Bavencio is approved in the U.S. as a second-line therapy for patients with locally advanced or metastatic urothelial carcinoma, whose disease progressed during or following platinum-based chemotherapy.

This indication was given accelerated approval, based on response to treatment and duration of responses. Full approval is contingent on further evidence of clinical benefit in confirmatory trials.

The global JAVELIN Bladder 100 Phase 3 trial (NCT02603432), which is examining Bavencio as a potential first-line maintenance therapy for patients achieving at least disease stabilization after platinum-based induction chemotherapy, was designed to provide that confirmation.

Bavencio was recently granted breakthrough therapy designation and is being reviewed by the U.S. Food and Drug Administration as a first-line maintenance treatment based on data from this trial.

JAVELIN is evaluating whether maintenance therapy with Bavencio plus best supportive care results in clinical benefits over best supportive care alone in patients showing a response or stable disease after first-line platinum-based chemotherapy.

Within 10 weeks of finishing chemotherapy, the trial’s 700 patients were randomized to Bavencio, given directly into the bloodstream every two weeks (a one-hour intravenous infusion), and best supportive care or best supportive care alone (control group). Treatment was given until disease progression, unacceptable toxicity, or withdrawal.

A total of 358 patients (51%) had PD-L1-positive tumors, and they were equally present in both the treatment and control groups.

The trial’s main goal is to assess overall survival in all patients, and in those with PD-L1-positive tumors. Secondary goals include the time a patient lives without signs of disease progression, the percentage of patients showing partial and complete responses to treatment, and safety.

At data cutoff (late 2019), patients had been followed for a median of 19.6 months in the Bavencio group, and for 19.2 months in the control group.

Results showed that JAVELIN met its primary goal, with Bavencio-treated patients living significantly longer than those receiving best supportive care alone (21.4 months vs. 14.3 months).

Notably, 71% of patients in the Bavencio group were alive at one year, compared with 58% of those in the control group.

Survival benefits were greater among patients with PD-L1-positive tumors, with a median overall survival of those given Bavencio not yet established (meaning that more than 50% of them were still alive at data cutoff), compared with 17.1 months for those in the control group.

These findings showed that Bavencio significantly lowered the risk of disease progression or death by 31% in the overall population, and by 44% in patients with PD-L1-positive tumors.

This survival benefit was observed in patients treated with different platinum-based chemotherapies, and regardless of chemotherapy response (disease stabilization, partial, or complete response).

Patients treated with Bavencio also lived significantly longer without signs of disease progression (3.7 months) than those treated with best supportive care (2 months), regardless of PD-L1 status. This difference meant that Bavencio caused a 38% reduction in the risk of disease worsening or death in the overall population, and a 44% lower risk among those with PD-L1-positive cancers.

Bavencio’s safety profile was manageable and consistent with that reported in previous trials, with no new adverse events. A greater proportion of patients in the Bavencio group experienced severe to life-threatening adverse events than those in the control group (47.4% vs. 25.2%), with the most common being urinary tract infection, anemia, blood in the urine, fatigue, and back pain.

After this interim analysis, control group patient have been allowed to cross to the Bavencio group.

“For the past 30 years, chemotherapy has been the first-line standard of care for patients with advanced urothelial carcinoma. While this is an effective short-term option for many patients, most will ultimately experience disease progression,” said Petros Grivas, MD, PhD, one of the trial’s principal investigators.

“Based on the positive overall survival results from JAVELIN Bladder 100, I believe avelumab has the potential to be practice-changing,” he added.