The 12-month recurrence-free survival rate was 42.9% for those who received BCG alone compared with 44.4% for those who received the combination.
Clinical outcomes, including delay to recurrence, were not significantly improved for patients with bacillus Calmette-Guérin-unresponsive non–muscle invasive bladder cancer undergoing treatment with a combination of the recombinant pox-viral vector vaccine Panvac and bacillus Calmette-Guérin (BCG).1
Results of the phase 2 study (NCT02015104) were presented at the 2021 American Urologic Association Annual Meeting.
Patients with high-grade NMIBC who did not respond to 1 or more induction courses of intravesical BCG were randomized to receive BCG (n = 15) or BCG plus Panvac (n = 15). The 12-month recurrence-free survival (RFS) rate was 42.9% (95% CI, 22.9%-80.0%) for those who received BCG alone compared with 44.4% (95% CI, 24.8%-79.9%) for those who received the combination (P = .971).
The median time to recurrence was 11.7 months vs 9.9 months, respectively (P = .77). The RFS rate for entire population was 43.3% (95% CI, 27.9%-66.8%).
The 12-month progression-free survival rates were 79.6% (95% CI, 56.9%-100%) and 78.6% (95% CI, 59.8%-100%) for patients treated with BCG alone and BCG plus Panvac, respectively.
Four patients from the BCG alone arm and 5 patients from the combination arm sought radical cystectomy following treatment.
In terms of baseline histologic characteristics, 14 patients had Ta, 7 had T1, 6 patients had carcinoma in situ alone, 2 had carcinoma in situ with Ta, and 1 had carcinoma in situ with T1. Additionally, 33% of patients (n = 10/30) had at least 2 prior induction courses of BCG.
The vaccine is designed to enhance the presentation of CEA and MUC-1, which are overexpressed in certain cancers, and activate cytotoxic T-lymphocyte response. The therapy consists of a recombinant vaccinia viral vector, a modified vaccinia Ankara-Bavarian Nordic, and a recombinant fowlpox vector. It is administered via a vaccinia priming dose, followed by multiple boosting doses of the fowlpox vector.2
Participants enrolled to the phase 2 trial received BCG in 6 weekly injections; those in the Panvac arm received the vaccine in 5 injections over 15 weeks.3
In the inclusion criteria for the study, investigators noted that all subclassifications for BCG failure would be considered for inclusion into the study, including BCG-refractory, -resistant, and -relapsing.
Investigators noted in the abstract that the trial was “unique” stating, “It originated prior to the definition of BCG-unresponsive disease and at least a third of the patients on this trial were already BCG unresponsive upon enrollment and received more BCG.”1
In a guidance for developing drugs and biologics for treatment, the FDA defined BCG-unresponsive disease as having at least 1 of the following characteristics: persistent or recurrent carcinoma in situ with or without recurrent Ta/T1 disease within 12 months of the completion of adequate BCG therapy, recurrent high-grade Ta/T1 disease within 6 months of the completion of adequate BCG therapy, and/or T1 high-grade disease at the first evaluation after a BCG induction course.4
Further, the FDA defined adequate BCG is defined as at least 5 of 6 doses of an induction course plus at least 2 of 3 doses of maintenance therapy, or at least 5 of 6 doses of an induction course plus at least 2 of 6 doses of a second induction course.4
“Unlike [ongoing] trials, this trial had a comparison group of BCG alone and, despite the heavy pretreatment in up to a third of patients, the RFS in both arms was still comparable to what has been seen in current BCG unresponsive trials,” the investigators concluded.1
The abstract was presented by Ragheed Saoud, MD, a urologist at Northwell Health in Riverside, New York.
1. Saoud R, Telfer S, Marfur M, et al. Clinical outcomes of a randomized, prospective, phase II study to determine the efficacy of bacillus Calmette-Guerin (BCG) given in combination with Panvac versus BCG given alone in adults with high grade BCG-refractory non-muscle invasive bladder cancer. J Urol. 2021;206(suppl3):e302. doi:10.1097/JU.0000000000002001.14
2. CEA-MUC-1-TRICOM vaccine CV301. National Cancer Institute. Accessed September 13, 2021. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/cea-muc-1-tricom-vaccine-cv301
3. Study of bacillus Calmette-Guerin (BCG) combined with Panvac versus BCG alone in adults with high grade non-muscle invasive bladder cancer who failed at least 1 course of BCG. ClinicalTrials.gov. Updated January 22, 2020. Accessed September 13, 2021. https://clinicaltrials.gov/ct2/show/NCT02015104
4. BCG-unresponsive nonmuscle invasive bladder cancer: developing drugs and biologics for treatment guidance for industry. FDA. 2018. Accessed September 13, 2021. https://www.fda.gov/media/101468/download