Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
University of Michigan Rogel Cancer Center
Enrollment:
36
Study Design:
This is a single arm, single center, phase II study of nab-paclitaxel and pembrolizumab in patients with platinum-refractory or cisplatin-ineligible advanced urothelial carcinoma. Eligible patients had RECIST 1.1 measurable disease. Patients were treated with nab-paclitaxel 125 mg/m2 IV on days 1 and 8 and pembrolizumab IV 200 mg in 21-day cycles Nab-paclitaxel could be discontinued after 6 cycles.
Rationale:
The current first-line standard of care for locally advanced or metastatic urothelial carcinoma is cisplatin-based combination chemotherapy. Despite responses in 50%-70% of patients in the first line setting, most eventually progress and median overall survival is about 14 months. For cisplatin ineligible patients OS is even worse, around 9 months.
Cisplatin-ineligibility or unresponsiveness to cisplatin presents a treatment challenge for patients. Pembrolizumab is an anti-PD-1 monoclonal antibody approved in the treatment of urothelial cancer after chemotherapy or in platinum ineligible patients who express PDL-1. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel; abraxane) does not require pre-medication and is also effective in platinum-refractory advanced urothelial carcinomas. This study evaluates the combination of pembrolizumab and nab-paclitaxel in patients with advanced urothelial carcinoma who are platinum-refractory or cisplatin-ineligible.
Endpoints:
The primary endpoint was overall response rate (ORR). Secondary endpoints include: duration of response, safety/toxicity, progression-free survival, and overall survival.
Comments:
In the Keynote 045 trial, after which pembrolizumab was registered as second line therapy, the median OS was 10.1 months in the pembrolizumab arm and superior to OS with chemotherapy. In the Keynote 052 trial of patients who were platinum ineligible, median OS with pembrolizumab was 11.3 months. In a phase II trial of Nab-paclitaxel median overall survival was 9.8 months. As it is always difficult to compare among trials, a median OS of 18.2 months in platinum refractory or cisplatin-ineligible patients with this combination is certainly promising and hypothesis generating. A phase III randomized trial of the combinaton versus Pembrolizumab is warranted.
Results:
Overall 36 patients were enrolled onto the study. There was an equal number of platinum-refractory and cisplatin-ineligible patients. The ORR was 50% (18/36) and tumor shrinkage was confirmed in 31 of 36 patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, the median duration of response was 4.4 months. Median PFS and OS were 6.8 months and 18.2 months, respectively. Of note, grade 3 or greater adverse events were noted in 21 of 36 patients. The combination was effective in patients refractory to or ineligible for cisplatin based chemotherapy albeit with some toxicity.
