This large, randomized controlled trial was completed at 12 international institutions.
Key eligibility criteria:
Age ≥18 y
Advanced UC of the renal pelvis, ureter, bladder, or urethra
Cisplatin ineligibility (ECOG PS 2, creatinine clearance ≥30 to <60 mL/min, grade ≥2 neuropathy or hearing loss, NYHA Class 3 heart failure)
No prior systemic chemotherapy for advanced UC
Measurable disease (RECIST v1.1)
ECOG PS 0-2
Provision of a tumor sample for biomarker analyses.
* Of note, 42% of patients were ECOG 2. 85% had visceral metastases. This is a very high-risk group.
Methods: Pembro 200 mg was administered every 3 weeks.
Imaging was performed at week 9, then every 6 weeks for the first year, and every 12 wk thereafter.
Outcomes: The primary end point was confirmed overall response rate (ORR; RECIST v1.1). This was completed as an independent review. Efficacy data are presented for patients with ≥4 mo follow-up. Safety data was a secondary endpoint.
Key Findings: (images not available)
370 patients enrolled.
- ORR was 24% for all patients
- In patients who were enrolled at least 4 months – 27%
- 58% had tumor size reduction
- Median time to response: 2 months
- 83% of patients had ongoing response
- Median response has not been reached
- 6% of patients achieved a complete response (CR)
- Essentially all subsets demonstrated benefit
- Biomarker specific for pembrolizumab = “combined positive score” (CPS)
- CPS ≥10% PD-L1 (tumor and immune cell PD-L1 expression) with ≥4 mo: ORR 44% (34%-55%)
- Noted that this group also had a higher CR rate ~10%
- Only 19 patients discontinued medication due to drug-related toxicity
These results are very exciting and are part of the new era of bladder cancer therapy.
This abstract won best poster in session.
Limitations / Discussion Points:
As Dr. Powles mentioned, the future discussion may not revolve around cisplatin eligibility, but rather biomarker positivity.
Presented by: Thomas Powles
Co-Authors: Bellmunt J., Castellano D., O’Donnell P., Grivas P., Vuky J., Plimack E., Hahn N., Balar A., Pang L., Savage M., Perini R., Keefe S., Bajorin D., De Wit R.
Institution(s): 12 International (European, UK, US) institutions
Written by: Thenappan Chandrasekar, Clinical Fellow, University of Toronto
at the #EAU17 -March 24-28, 2017- London, England