EAU 2017: Updated meta-analysis (MA) of salvage therapy for metastatic urothelial cancer (mUC): Comparing outcomes of immunotherapy (IT) vs. single agent and doublet chemotherapy (CT)

London, England (UroToday.com) The management of metastatic urothelial carcinoma is undergoing rapid changes. With the introduction of immunotherapy, chemotherapy is no longer the only option. The authors conduct an updated meta-analysis of the treatment options for metastatic urothelial carcinoma (mUC) using the PICO strategy, comparing immunotherapy (IT), single-agent chemotherapy (singlet) and double-agent chemotherapy (doublet). This included arms of larger studies. Primary outcomes were: objective response rate (ORR), median progression free survival (PFS), and median overall survival (OS). They did their due diligence and accounted for publication bias.

*Of note, the abstract was updated prior to presentation at the conference.

Ultimately, eight IT trials were analyzed (n=1,311), 22 arms received single agent CT (n=1,202), and 24 doublet CT (n=708). Subsequent pooled analyses were used to compare the different treatment options against each other. Initially, they included the one phase 3 randomized double blind study in the immunotherapy arm; however, secondary analyses looked at only phase 1 and 2 studies. Of note, the presence of liver metastases and ECOG PS 2 were covariates in the analysis, and were accounted for. In the entire cohort of studies, IT and doublet therapy were superior to singlet therapy for ORR. IT therapy was inferior to both singlet and doublet therapy with regards to PFS, while doublet was superior to singlet. Lastly, for OS, IT was superior to singlet therapy, but equivalent to doublet therapy. On subset analysis with removal of the one double-blind phase 3 trial (unclear why this assessment was needed), the findings for ORR were unchanged, but the differences between the three therapies for PFS and OS were lost. found to improve ORR.

Table 4 highlighted the final pooled ORR, PFS, and OS for IT therapy, IT therapy in PD-L1+ patients, singlet chemotherapy and doublet chemotherapy. Doublet chemotherapy had the highest ORR and PFS, while IT in PD-L1+ patients had the highest OS.

Lastly, they highlight the differences in response probability, PFS and OS between all patients treated with IT versus those who were PD-L1+ treated with IT. Unfortunately, while the PFS and OS were slightly higher in patients who were PD-L1+, there is little explanation for the results themselves.

Ultimately, however, the authors were hard-pressed to make any strong conclusions. This study doesn’t change clinical practice at this point, especially in the absence of phase 3 RCTs.

Speaker(s): A. Necchi

Co-Authors: Raggi D., Sonpavde G., Giannatempo P., Mariani L., Galsky M., Bellmunt J., Miceli R.

Institution(s): 1. Fondazione IRCCS - Istituto Nazionale Dei Tumori, Dept. of Medical Oncology, Milan, Italy
2UAB Comprehensive Cancer Center, Dept. of Medical Oncology & Hematology, Birmingham, United States of America
3. Fondazione IRCCS Istituto Nazionale Dei Tumori, Dept. of Medical Oncology, Milan, Italy
4. Fondazione IRCCS Istituto Nazionale Dei Tumori, Clinical Epidemiology and Trials Organization Unit, Milan, Italy
5. Mount Sinai School of Medicine, Tisch Cancer Institute, Dept. of Medical Oncology, New York, United States of America
6. Dana-Farber Cancer Institute and Harvard Medical School, Dept. of Medical Oncology, Boston, United States of America

Written By: Thenappan Chandrasekar, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 - March 24-28, 2017- London, England
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