ASCO GU 2018: Best of Journals: Urothelial Carcinoma - Medical Oncology

San Francisco, CA ( Dr. Andrea Apolo, a medical oncologist form the National Cancer Institute presented multiple high-impact journal articles from the last 13 months that are particularly important to medical oncologists.  She believes we are in the “golden era” of the development of systemic therapy for patients with advanced urothelial carcinoma. 

Over the last year, the standard of care of advanced urothelial carcinoma has changed dramatically, with the approval of five new immunotherapy agents.  Dr. Apolo reviewed the trials that lead to these drug approvals. 

She began by discussing the IMvigor211 study, which lead to approval of atezolizumab.  In this phase III trial, patients with metastatic urothelial carcinoma who progressed despite first line chemotherapy were randomized to receive either atezolizumab or a second-line chemotherapy regimen of the investigator's choice.  The primary endpoint was median overall survival (OS).  They found that median OS for the atezolizumab group was 11.1 months, while the OS for the second-line chemotherapy group was 10.6 months (p = 0.41), indicating there was no survival benefit for the use of atezolizumab.  It received FDA approval, however, because it certainly does have activity in the treatment of metastatic urothelial carcinoma.  The study also highlighted the fact that patients who have tumor-infiltrating immune cells that express PD-L1 tended to have a better response to atezolizumab.

She next highlighted the KEYNOTE-045 study which lead to FDA approval of pembrolizumab. In this large, phase III trial, 542 patients with metastatic urothelial carcinoma who progressed despite first line chemotherapy were randomized to receive either pembrolizumab or second line chemotherapy.  The median OS for patients receiving pembrolizumab was 10.3 months versus 7.4 months for those patients receiving second line chemotherapy (p = 0.0003). This study also showed that patients whose tumors expressed elevated levels of PD-L1 tended to have worse responses to chemotherapy and PD-L1 inhibitors. 

Dr. Apolo then discussed a phase II trial which led to the approval of durvalumab.  The most significant finding from this study was that when patients were stratified by PD-L1 expression, it directly correlated with overall survival.  Those patients with high PD-L1 expression showed an improved OS, and there were more complete responders in this group. 

She finished by reviewing the data from the JAVELIN solid tumor trial which evaluated the efficacy of avelumab, an anti-PDL-1 antibody, in 249 patients with metastatic urothelial carcinoma who had already received platinum based chemotherapy. They found that 39 patients had a 16,1% objective response rate to this agent (12 complete responses, 27 partial responses). The median time to response was 11.7 weeks, and the median duration of response was 20.1 months.  It is notable that the duration of responses lasting greater than 12 months was 70.3%. 

Dr. Apolo concluded the standard of care of bladder cancer has rapidly evolved in the last 12 months, and continues to do so as these agents are being tested in combination therapy, as well as in earlier stages of the disease.  She believes that we will have even more compelling data about how to optimize the treatment of metastatic bladder cancer in the coming 12 months. 

Presented by: Andrea Apolo, MD, National Cancer Institute

Written by: Brian Kadow, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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