ORLANDO (FRONTLINE MEDICAL NEWS)A combination of intravesical bacillus Calmette-Guerin (BCG) followed by sunitinib produced high complete response rates in patients with high-risk, non–muscle invasive bladder cancer.

In a phase II trial, 26 of 36 patients (72%) with non–muscle invasive bladder cancer (NMIBC) had a complete response following bladder installation of BCG and consolidation therapy with sunitinib (Sutent), reported Dr. Alexander M. Helfand of the University of Michigan Comprehensive Cancer Center, Ann Arbor.

“Adding sunitinib after BCG induction may result in increased rates of complete response at 3 months over those of BCG alone. The durability of response appears promising, given a 77% 2-year recurrence in high-risk patients with non–muscle invasive bladder cancer,” he said at the 2015 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology.

“Certainly, this study provides the rationale to consider antiangiogenic therapy in the non–muscle invasive setting,” said Dr. Jonathan E. Rosenberg of Memorial Sloan Kettering Cancer Center, New York, the invited discussant.

Induction and maintenance therapy with BCG is the mainstay of initial treatment of high-risk NMIBC. It has been associated in clinical studies with 3-month complete response rates ranging from 28% to 85%, 5-year cumulative recurrence rates from 50% to 55%, 5-year cumulative progression rates of 8%-20%, and a 10-year disease-specific mortality rate of 4%-25%, Dr. Helfand noted.

“Complete response to BCG at 3 months has been shown to predict future recurrence-free status. Consolidating the initial tumor response to BCG with adjunctive therapies may help improve outcomes,” he said.

BCG downregulates vascular endothelial growth factor (VEGF) receptors, and sunitinib binds to VEGF receptors to prevent vascular growth.

To see whether the combined therapies could act synergistically, investigators treated patients with 6-weeks of BCG induction beginning within 6 weeks of diagnostic or restaging biopsy, followed by a 2-week hiatus, then 28 days of oral sunitinib 50 mg/day. Patients with a complete response at 3 months went on to BCG maintenance, while those with an incomplete response or recurrence at 3 months went on to a second cycle of BCG followed by sunitinib. Patients with disease progression after either treatment cycle were treated with alternative therapies at the treating clinician’s discretion.

A total of 36 of 39 patients completed BCG induction and at least one dose of sunitinib, and these patients were included in the efficacy analysis. The safety analysis was by intention to treat, and therefore included all 39 patients.

The complete response rate at 3 months after cycle one, the primary endpoint, was 73% (26 of 36 patients). Of the responders, 73% have started on BCG maintenance, 23% had no maintenance BCG and no evidence of disease at last follow-up, and the remaining 4% had cystectomies.

Of the 28% (10 patients) with residual disease at 3 months, four underwent cystectomy, two had Ta low-grade recurrences which were managed with repeat resection, and two elected a second BCG induction/sunitinib cycle.

There were a total of 127 adverse events deemed to be minor among 34 patients, and 6 major adverse events occurring in 5 patients. The major events included rash on hands and feet, hand and foot syndrome, thrombocytopenia, febrile diarrhea, sores on hands and feet, and reactivation of herpes zoster.

In all, 13 patients required some delay of sunitinib therapy, primarily due to jaundice/elevated liver enzymes or thrombocytopenia. All adverse events disappeared at the end of therapy.

Of the 31 patients with an intact bladder, 2 years recurrence-free survival was 77%, and 2-year progression-free survival was 100%.

Dr. Rosenberg, the discussant, noted that overall “the results look quite good. Toxicity and tolerability, though, do make me concerned, and future trials might consider dose reduction [of sunitinib] at the start to 37.5 mg to actually increase the number of patients and time on therapy.”