Last year, initial outcomes of the phase II KEYNOTE-052 study reported that among 370 patients receiving at least one dose of pembrolizumab, 89 (24%, 95%CI 20-29) patients had a centrally assessed objective response, and 74 (83%) of 89 patients had ongoing responses over a median follow-up of 5 months (IQR 3.0-8.6) . Additionally, a PD-L1-expression cutoff of 10% was associated with a higher frequency of response to pembrolizumab: 42 (38%, 95%CI 29-48) of 110 patients had an objective response. Based on these results, pembrolizumab was granted FDA approval for the treatment of cisplatin-ineligible patients with advanced urothelial carcinoma. In the first-line cisplatin ineligible patient, Dr. North concluded:
- Pembrolizumab and atezolizumab have promising results
- These agents are approved in the US for these indications, but are not currently approved in Canada – no immunotherapy agent is approved or available for cisplatin ineligible as a first line treatment in Canada
- In Canada, medical oncologists are left to either pursue clinical trials or carboplatin-based therapy
- Cisplatin eligible patients are still treated with chemotherapy in the first-line
- This was a negative phase III trial for OS in the second line setting, although a confounding factor is that the chemotherapy group did better than expected and the benefit seems to be driven by vinflunine
- Atezolizumab appears to still be better than taxanes, which is what would commonly be used in the second-line setting since vinflunine is not approved in North America
- Further investigation of post-protocol treatment may be informative to assess if there are differences based on what chemotherapy was given
- Atezolizumab is still a viable option in the Canadian context, although funding will be an uphill battle with the negative phase III trial
Dr. North notes that there are multiple first-line trials underway/completed enrolling, including DANUBE (durvalumab vs durvalumab/tremelimumab vs chemotherapy) and IMvigor 130 (atezolizumab vs chemotherapy vs atezolizumab/chemotherapy). He concluded with several summary points:
- There are promising results seen using immunotherapy in the first-line setting for cisplatin ineligible patients but drugs are currently not available in Canada in this setting
- Pembrolizumab has become the standard of care second-line agent given the positive KEYNOTE-045 study
- Atezolizumab is an active agent and further review of the IMvigor 211 trial will be needed to understand its results
- Access programs in the second-line setting exist for pembrolizumab and durvalumab pending an approval process
- Many trials are completed and waiting to report in the first-line setting
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre Twitter: @zklaassen_md at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia
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