Adding PANVAC to BCG does not improve recurrence-free survival in BCG-refractory NMIBC

Data from a phase 2 trial (NCT02015104) published in Urologic Oncology showed no improvement in recurrence-free survival (RFS) when PANVAC, a recombinant poxviral vector vaccine, was added to BCG in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC).¹

“We hypothesized that PANVAC co-administration would augment the BCG-induced cytotoxic T-lymphocyte response against bladder cancer cells overexpressing MUC-1 and/or CEA and lead to reduced rates of recurrence and progression,” the authors wrote.

In total, the study included 30 patients with high-grade NMIBC who had failed at least 1 induction course of intravesical BCG. Patients were randomly assigned to receive BCG plus PANVAC (n = 15) or BCG alone (n = 15). The median age of patients was 75 years (IQR, 68.8 to 79.6). The primary end point was RFS, with progression-free survival (PFS) and radical cystectomy-free survival as key secondary end points.

Data no significant difference in the RFS between arms, with a median RFS of 12.6 months in the BCG alone arm vs 10.7 months in the BCG plus PANVAC arm (P = .7). At 12 months, the RFS rate was 53.3% in the BCG alone arm vs 40% in the combination arm (P = .3).

BCG-unresponsive status at baseline was found to be predictive of recurrence, with a hazard ratio of 2.6 (95% CI, 1.07 to 6.3; P = .03). In patients who met the criteria for BCG-unresponsive disease, the median RFS was 4.4 months compared with 12.6 months among those who did not meet the criteria (P = .03). The presence of carcinoma in situ or T1 disease, as well as baseline purified protein derivative (PPD) status, were not predictive of RFS.

The trial also showed no significant differences between arms on the study’s secondary end points. At a median follow-up of 36.2 months, 30% of patients developed disease progression, which included 3 patients in the BCG alone arm and 6 patients in the combination arm.

The median time to progression was 34.6 months in the BCG alone arm vs 36.2 months in the BCG plus PANVAC arm; the difference did not meet statistical significance (P = .9). There was also no significant difference in PFS when patients were stratified by BCG-unresponsive status (NR in BCG-unresponsive patients vs. 34.6 months; P = 0.7).

A total of 11 patients underwent radical cystectomy, which included 4 patients in the BCG alone arm and 7 patients in the combination arm. The median time to radical cystectomy was 34.6 months in the control arm vs 36.1 months in the combination arm (P = .6). There was no significant difference in cystectomy-free survival based on baseline BCG-unresponsive status.

In total, 93.3% of patients (n = 28) experienced at least 1 adverse event (AE), which included 13 patients in the BCG alone arm and 15 patients in the combination arm. The most common AEs included hematuria, injection-site reaction, fatigue, dysuria, proteinuria, and urgency/frequency. AEs were generally minor, with grade 3 AEs reported in 3 patients in each arm. There were no grade 4 or 5 AEs or treatment discontinuations due to AEs.

The investigators also explored immune markers and showed no evidence of increased T-cell tumor infiltration with the addition of PANVAC.

“There was a slightly higher PPD seroconversion rate in the combination arm, suggesting activation of the immune system, but no measurable clinical benefit,” the authors noted. “The differing results [in bladder cancer], compared to the positive outcomes observed in breast and colorectal cancers, might be attributed to the disease settings in which PANVAC was tested—localized vs. metastatic disease.”

The authors suggested that a greater treatment effect may be observed with a more antigenic vaccine.

“A larger sample size with a longer follow-up, decreased tumor and pretreatment heterogeneity, and a higher frequency of expressed TAAs may improve outcomes in future studies of cancer vaccine therapy,” the authors concluded.

REFERENCE

1. Ho M, Lazarovich A, Saoud R, et al. Bacillus Calmette-Guérin (BCG) in combination with PANVAC™ vs. BCG alone in adults with high-grade BCG-refractory non-muscle-invasive bladder cancer. Urol Oncol. 2025;43(11):660.e1-660.e10. doi:10.1016/j.urolonc.2025.06.006