MedicalResearch.com Interview with:
Arjun Balar, M.D.
Assistant Professor of Medicine
Director – Genitourinary Medical Oncology Program
NYU Perlmutter Cancer Center
New York, NY 10016
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Standard treatment for advanced urothelial cancer includes cisplatin-based chemotherapy which has been shown to improve survival. But more than half of patients are not expected tolerate it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative to cisplatin. Pembrolizumab is a PD-1 blocking antibody that reactivates the body’s cancer-fighting T-cells (part of the immune system) to fight urothelial cancer.
The trial overall enrolled 374 patients who had not yet received any treatment for advanced urothelial cancer, but were considered ineligible for cisplatin chemotherapy.
I presented the data for the first 100 patients as part of a planned interim analysis. The key findings were that pembrolizumab led to a 24% objective response rate, and 6% complete response rate. Of the patients who achieved an objective response, the median duration of response had not yet been reached at a median follow up time of 8 months. Another key objective of the study was to evaluate in tumor specimens collected from these patients the level of PD-L1 expression that identified the patients most likely to pembrolizumab treatment. In this study, the PD-L1 expression level was calculated as the percentage of PD-L1 expressing tumor cells and immune cells, over the total number of tumor cells. 30 of the 100 patients had an expression level of 10%, and in those patients, the objective response rate was 37% and complete response rate was 13%. Additionally, 23% of those patients achieved stable disease. Thus, the 10% level seemed to identify the patients most likely to respond to pembrolizumab, however it is important to note that even amongst the patients who had <1% expression, the objective response rate was 18%. These data will need to be validated in the remaining 274 patients enrolled in this trial to know for sure how well the 10% cut-off works.
Treatment with pembrolizumab was very well tolerated, with only 16% of patients developing grade 3 or 4 treatment-related toxicity and 5% of patients discontinuing treatment due to toxicity. Also, no treatment related deaths occurred. In contrast, roughly 20% of patients will discontinue carboplatin-based treatment due toxicity. Further, immune-related toxicities from pembrolizumab treatment were manageable.
MedicalResearch.com: What should readers take away from your report?
Response: The preliminary data from this important trial confirm that immunotherapy is active, well-tolerated and leads to durable responses in patients with metastatic urothelial cancer who are ineligible for cisplatin-based chemotherapy. Given that most patients in this group are often too sick or frail to receive aggressive chemotherapy (in fact 34% of the patients in this analysis were age 80 or greater and 87% had spread of cancer to liver, lung and/or bone), pembrolizumab is a very attractive treatment option in this setting. Longer follow up in these patients as well as outcomes from the remaining 274 patients are eagerly awaited to truly define the role for first-line pembrolizumab in metastatic urothelial cancer.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The development of inhibitors targeting the PD-1 signaling pathway are rapidly reshaping our treatment approach for patients with advanced urothelial cancer and will soon become a major component of our armamentarium. Our attention is now being directed toward addressing how we can improve upon single agent PD-1 treatments to further enhance the cancer-fighting power of the immune system. Combination approaches utilizing other immune checkpoint inhibitors and/or immune activators as well as conventional cancer therapies such as radiation and chemotherapy in advanced as well as localized urothelial cancer are currently being investigated in clinical trials. The key is that we continue to strive to improve outcomes for all patients afflicted with this dreadful disease.
MedicalResearch.com: Is there anything else you would like to add?
Response: This is a very hopeful and promising time for patients with urothelial cancer and I am confident that we will continue to make even greater advances toward making more efficacious well tolerated treatments in the near future.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation: ESMO abstract: KEYNOTE-052: Phase 2 study of pembrolizumab (MK-3475) as first-line therapy for patients (pts) with unresectable or metastatic urothelial cancer ineligible for cisplatin-based therapy.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
More Medical Research Interviews on MedicalResearch.com