AUA 2021: Clinical Outcomes of a Randomized, Prospective, Phase II Study to Determine the Efficacy of BCG Given in Combination with PANVAC™ vs BCG Alone in Adults with High Grade BCG-Refractory NMIBC

( Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with Bacillus Calmette Guerin (BCG) is guideline-recommended on the basis of proven benefits in disease recurrence. While BCG is efficacious, many patients eventually develop BCG-unresponsive disease. Despite guideline-concordant care, many patients with BCG-unresponsive NIMBC are at significant risk for recurrence and progression. For many years, there have been very limited options for these patients. Radical cystectomy has remained the gold standard even though numerous approaches including intravesical and systemic therapies have been investigated.

In a moderated poster presentation at the American Urologic Association (AUA) Virtual Annual Meeting, Dr. Saoud and colleagues presented results of a prospective phase II clinical trial of BCG alone or BCG combined with a recombinant pox-viral vector vaccine, PANVAC™, in patients with NMIBC who have failed a prior treatment of intravesical BCG (NCT02015104).

This randomized, open label prospective, phase II study enrolled patients with high-grade NMIBC who failed at least one induction course of intravesical BCG. Enrolled patients were then randomized to either BCG alone or BCG+PANVAC™. All subjects received intravesical BCG for a total of 6 weeks. Patients in the combination arm also received priming and booster doses of PANVAC™. Patients were followed for 1 year. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included progression-free survival (PFS). Exploratory secondary immunological response endpoints were evaluated on the trial as well.

At the time of this report, 32 patients were enrolled and two withdrew. Thus, a total of 30 patients (15 in each arm) were included. There were 6 patients with carcinoma in-situ (CIS) alone, 2 with Ta + CIS, 1 with T1 + CIS, 14 with Ta, and 7 with T1. Of these, 10/30 (33%) had 2 or more prior induction courses of BCG. There was no statistically significant difference in baseline patient characteristics between the BCG alone and the BCG+PANVAC™ groups.

At 12 months following index, the overall RFS rate was 43.3% (CI 27.9-66.8). The 12-month RFS rate was 42.9% (22.9-80.0) in patients who received BCG alone and 44.4% (CI 24.8-79.7) in those who received BCG+PANVAC™ (p=0.971). Median time to recurrence was similar (11.7 vs 9.9 months; p=0.77) in both arms. In the BCG arm, the 12-month PFS rate was 79.6% (CI 56.9-100) while it was 78.6% (95% CI 59.8-100) in the BCG+PANVAC™ arm. Following the 12 month trial duration, 9 patients (30%) sought radical cystectomy, 4 after BCG alone and 5 after BCG + PANVAC™.

Dr. Saoud thus concluded that these phase II trials demonstrate no improvement in RFS with the addition of PANVAC™ to BCG alone in patients with NMIBC who have failed to respond to intravesical BCG. Unlike many trials in this disease space, this trial included an active comparator though the majority of patients were already BCG-unresponsive at the time of enrollment.

Presented by: Ragheed Saoud, MS, Urologic Oncology Fellow, University of Chicago

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.


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