From a study design standpoint, the study is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria are defined as follows: males with a diagnosis of high-risk NMIBC (T1 tumor, Grade 3, CIS, multiple and recurrent and large (>3 cm) Ta tumors, G1G2 tumors or patients in the last EAU recurrence category EAU/EORTC recurrence score >/=10), and between age 40 and 75 years.
Planned accrual is 200 patients.
Eligible patients were then randomized into two groups:
1) BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with 81 mg Connaught strain BCG
2) BCG treatment with the same protocol but including an additional 40 mg mitomycin instillation the day before BCG treatment.
They planned to assess response using cystoscopy and urine cytology every 12 weeks for 2 years. The primary endpoints were intravesical recurrence, while secondary endpoints were overall toxicity.
Accrual began March 2019; to date, they have enrolled 36 patients.
Overall, 15 (42%) patients were randomized to sequential combination therapy and 21 (48%) to BCG monotherapy.
After induction treatment, six patients experienced a post-treatment AE, three (50%) in the sequential combination therapy arm and three (50%) in the BCG monotherapy arm. Five AEs (urethral sub-stenosis, fever, asthenia, fainting, cystitis) were CTCAE grade 1 and did not require further treatment. There was one Grade 3 AE - acute epididymo-orchitis with abscess requiring orchiectomy in the monotherapy BCG group.
No significant differences were found between the two groups (Table) in terms of QOL and AE outcomes.
They will continue recruiting to the study.
Presented by: Cosimo De Nunzio, MD, Ph.D., Department of Urology at Sant' Andrea Hospital in Rome, Italy
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.