Shilpa Gupta, MD, associate professor of medicine, Hematology/Oncology and Transplantation Division, University of Minnesota, discusses the results of the phase I/Ib trial investigating the use of frontline enzalutamide, gemcitabine and cisplatin in metastatic bladder cancer.
Shilpa Gupta, MD, associate professor of medicine, Hematology/Oncology and Transplantation Division, University of Minnesota, discusses the results of the phase I/Ib trial (NCT02300610) investigating the use of frontline enzalutamide (Xtandi), gemcitabine, and cisplatin in metastatic bladder cancer.
Investigators assessed the activity of the androgen receptor (AR) inhibitor enzalutamide because the AR pathway is upregulated in bladder cancer. In the dose-escalation phase, 6 patients received enzalutamide at a dose of 80 mg or 160 mg in combination with gemcitabine and cisplatin. After 6 cycles of treatment, continued maintenance with enzalutamide was administered. In the dose-expansion cohort, 4 patients received the 160 mg dose of enzalutamide as no dose-limiting toxicities were reported in the dose-escalation phase. Notably, the dose-expansion cohort was limited to AR-positive patients, says Gupta.
Results showed the regimen was well tolerated in patients and toxicities were as expected. Of the 8 evaluable patients from both cohorts, 1 patient with AR expression >90% had a complete response. Three years later, the patient remains in remission, reports Gupta. Further, 4 patients had a partial response, 2 had stable disease, and 1 had progressive disease. The triplet therapy induced a median overall survival was 10.59 months and a median progression-free survival of 7.68 months.
Although immunotherapy has revolutionized bladder cancer treatment in recent years, targeted therapy is largely unexplored, says Gupta. She is hopeful for further exploration into targeted therapy with AR inhibitors and combination therapy with immunotherapy.