ORLANDO, Fla.—Intravesical bacillus Calmette-Guérin (BCG) followed by sunitinib shows promise as a treatment for high-risk nonmuscle-invasive bladder cancer (NMIBC), according to the findings of a phase 2 trial presented at the 2015 Genitourinary Cancers Symposium.

Alexander M. Helfand, BA, Alon Weizer, MD, MS, principal investigator, and colleagues at the University of Michigan in Ann Arbor, presented results from 36 evaluable patients with a median age of 65.9 years who received the combined treatment for high-grade clinical NMIBC without lymph node involvement or distant metastases.

The patients received BCG induction followed 2 weeks later by 28 days of treatment with sunitinib 50 mg. The primary outcome was complete response based on biopsy and cytology at 3 months. If 25 or more of the patients achieved a 3-month complete response, then the treatment would be considered for further study, according to the investigators.

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The initial cancer stage was T1 in 19 patients, Ta in 9, and carcinoma in situ in 8. Thirteen patients had a treatment delay for a median of 12 days and a dose reduction to 37.5 mg. Of the 36 patients, 26 (72%) had a complete response at 3 months. One patient completed a second cycle of BCG plus sunitinib for incomplete response and had a complete response at 6 months. BCG maintenance therapy was administered to 21 patients. The study population had a 77% rate of 2-year recurrence-free survival.

A total of 133 adverse events (AE) occurred in 34 patients, including 6 AEs in 5 patients that were grade 3 or higher: thrombocytopenia, diarrhea, shingles, extremity rash/pain and hand-foot syndrome.

“There is certainly a role for complementary therapies alongside BCG in order to improve complete response, which has been shown to predict future recurrence and progression of disease,” said Helfand, who is a fourth-year medical student.

The researchers concluded that BCG plus sunitinib may produce outcomes superior to BCG alone.

“BCG induction and maintenance therapy have been the mainstay of treating high-risk nonmuscle-invasive bladder cancer for 30 years,” Helfand said. “But in essence we haven’t been able to improve on rates of complete response with BCG after induction. We were seeking a way to try to find a compound that would work as a complementary therapy to BCG. What we decided to do was to use sunitinib, which would complement the anti-angiogenic effects of BCG on urothelial tumor cells. Using a VEGF inhibitor like sunitinib would perhaps enable complete response over that of BCG alone.”

“The promising results of this trial provide data that anti-angiogenic agents may be useful tools for lessening the burden of non-muscle invasive bladder cancer recurrence and intervention,” said Dr. Weizer, associate professor of urology and medical director of the University of Michigan Comprehensive Cancer Center, said, 

The study was supported by Pfizer, Inc.