Purpose Sunitinib is a vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity against bladder cancer. We hypothesized that treatment with sunitinib may decrease progression or recurrence in non-muscle invasive bladder cancer (NMIBC) refractory to intra-vesical BCG. Patients and Methods This is a single-arm phase II study of sunitinib in patients (pts) with NMIBC who progressed after BCG. Treatment included sunitinib 37.5 g daily for 12 weeks followed by 12± 2-week cystoscopy and surveillance for one year. The primary endpoint was the complete response rate at 12 months. Secondary endpoints included recurrence free survival (RFS), progression free survival (PFS), overall survival (OS), and safety of sunitinib. Correlative studies on effects of sunitinib on myeloid derived suppressor cells (MDSC) and humoral immune responses were also performed. This trial was registered on ClinicalTrials.gov , number NCT01118351. Results Between June 2011 and September 2011, 15/19 pts. completed 12 weeks of therapy. The remaining 4 pts. had treatment related adverse events leading to discontinuation of sunitinib with one patient withdrawing consent. On the 12-week cystoscopy, 44% (8/18) of the pts. showed remission, 50% (9/18) progression and 1/18 recurrence. Overall, 22% (4/18) of pts. remained free of progression for >12 months. Grade (G) 4 toxicities were noted in 2 pts. (anemia and thrombocytopenia) while G3 were noted in 58%. Sunitinib resulted in reversal of MDSC mediated immunosuppression. Conclusions In NMIBC refractory to BCG, treatment with sunitinib was safe but not associated with improved clinical outcomes. The immune effects of sunitinib deserve further investigation.

Investigational new drugs. 2019 Jun 24 [Epub ahead of print]

Haris Zahoor, Maria C Mir, Pedro C Barata, Andrew J Stephenson, Steven C Campbell, Amr Fergany, Robert Dreicer, Jorge A Garcia

Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA., Urology Department, IMED Valencia Hospital, Valencia, Spain., Department of Internal Medicine, Section of Hematology and Medical Oncology, Tulane Medical School, New Orleans, Louisiana, USA., Cleveland Clinic, Glickman Urological and Kidney Institute, 9500 Euclid Avenue/R35, Cleveland, OH, 44195, USA., Division Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Cleveland Clinic, Glickman Urological and Kidney Institute, 9500 Euclid Avenue/R35, Cleveland, OH, 44195, USA. .