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Comparative Effectiveness of Immune Checkpoint Inhibitors in Patients with Platinum Refractory Advanced Urothelial Carcinoma

2020; Lippincott Williams & Wilkins; Volume: 205; Issue: 3 Linguagem: Inglês

10.1097/ju.0000000000001412

1527-3792

Umang Swami, Benjamin Haaland, Adam Kessel, Roberto Nussenzveig, Benjamin L. Maughan, John Esther, Deepika Sirohi, Sumanta K. Pal, Petros Grivas, Neeraj Agarwal,

Cancer Immunotherapy and Biomarkers

No AccessJournal of UrologyAdult Urology1 Mar 2021Comparative Effectiveness of Immune Checkpoint Inhibitors in Patients with Platinum Refractory Advanced Urothelial CarcinomaThis article is commented on by the following:Editorial Comment Umang Swami, Benjamin Haaland, Adam Kessel, Roberto Nussenzveig, Benjamin Louis Maughan, John Esther, Deepika Sirohi, Sumanta K. Pal, Petros Grivas, and Neeraj Agarwal Umang SwamiUmang Swami Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah , Benjamin HaalandBenjamin Haaland Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah Department of Population Health Sciences, University of Utah, Salt Lake City, Utah , Adam KesselAdam Kessel Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah , Roberto NussenzveigRoberto Nussenzveig Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah , Benjamin Louis MaughanBenjamin Louis Maughan Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah , John EstherJohn Esther Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah , Deepika SirohiDeepika Sirohi Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, Utah , Sumanta K. PalSumanta K. Pal Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California , Petros GrivasPetros Grivas ¶Correspondence: Clinical Research Division, Fred Hutchinson Cancer Research Center, 825 Eastlake Ave. E, Seattle, Washington 98109-1024 (FAX: 206-606-2042; E-mail Address: [email protected] and Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington , and Neeraj AgarwalNeeraj Agarwal ¶Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr., Suite 5726, Salt Lake City, Utah 84112 telephone: 801‐213‐5658; E-mail Address: [email protected] Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah View All Author Informationhttps://doi.org/10.1097/JU.0000000000001412AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Five programmed cell death protein 1 or its ligand (L1) inhibitors are approved for treatment of platinum refractory, locally advanced/unresectable or metastatic urothelial carcinoma. However, their comparative effectiveness is unknown. We compared time to initiation of third therapy or death, and overall survival with different programmed cell death protein 1/L1 inhibitors in patients with platinum refractory metastatic urothelial carcinoma. Materials and Methods: Patient-level data were extracted from a real-world de-identified database. Comparative effectiveness was inferred via Cox proportional hazards model, weighted by matching weights. Each patient's propensity for each treatment was modeled via random forest, based on potential drivers of treatment selection. A propensity score for each therapy was used to calculate a matching weight, targeting the same estimand as 1:1 matching of treatment groups with balance among potential confounders. Eligibility criteria included diagnosis of metastatic urothelial carcinoma, receipt of first line treatment with a platinum based chemotherapy, followed by initiation of single agent programmed cell death protein 1/L1 inhibitor after disease progression from August 1, 2016 through May 1, 2019. Results: Overall, 609 patients were eligible for analysis. Median time to initiation of third therapy or death with atezolizumab, nivolumab and pembrolizumab was 4.2, 5.3 and 4.5 months, respectively, and median overall survival was 6.4, 8.0 and 8.3 months, respectively. Matching weighted analyses did not show strong evidence of differences among programmed cell death protein 1/L1 inhibitors in terms of time to initiation of third therapy or death and overall survival. Conclusions: In this large real-world cohort, effectiveness in terms of time to initiation of third therapy or death and overall survival with programmed cell death protein 1/L1 inhibitors in patients with platinum refractory locally advanced/unresectable or metastatic urothelial carcinoma was similar. References 1. National Comprehensive Cancer Network: Bladder Cancer (Version 3.2020). Avialable at https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed April 5, 2020. Google Scholar 2. : Integration of immunotherapy into the treatment of advanced urothelial carcinoma. J Natl Compr Canc Netw 2020; 18: 355. Google Scholar 3. : Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules 2019; 24: 1190. Google Scholar 4. : Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 2, immune checkpoint inhibitor antibodies. Eur J Cancer 2020; 128: 119. Google Scholar 5. : Immunological correlates of response to immune checkpoint inhibitors in metastatic urothelial carcinoma. Target Oncol 2018; 13: 599. Google Scholar 6. : Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron health, SEER, and NPCR. medRxiv. 2020; doi: 2020.03.16.20037143. Crossref, Google Scholar 7. : Matching weights to simultaneously compare three treatment groups: comparison to three-way matching. Epidemiology 2017; 28: 387. Google Scholar 8. : A weighting analogue to pair matching in propensity score analysis. Int J Biostat 2013; 9: 215. Google Scholar 9. : Random forests. Machine Learn 2001; 45: 5. Google Scholar 10. : Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387: 1909. Google Scholar 11. : Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2017; 18: 312. Google Scholar 12. : Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol 2017; 3: e172411. Google Scholar 13. : Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase ib study. J Clin Oncol 2017; 35: 2117. Google Scholar 14. : Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017; 376: 1015. Google Scholar 15. : Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. J Clin Oncol, suppl., 2020; 38: LBA1. Google Scholar 16. : Programmed death-1 or programmed death ligand-1 blockade in patients with platinum-resistant metastatic urothelial cancer: a systematic review and meta-analysis. Eur Urol 2019; 76: 782. Google Scholar 17. : Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer—a systematic review and network meta-analysis of 3024 participants. Lung Cancer 2018; 115: 84. Google Scholar 18. : Comparative-effectiveness of pembrolizumab vs. nivolumab for patients with metastatic melanoma. Acta Oncol 2020; 59: 434. Google Scholar 19. : Five-factor prognostic model for survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-L1 inhibitors. J Urol 2020; 204: 1173. Link, Google Scholar Supported by the National Cancer Institute of the National Institutes of Health under Award No. P30CA042014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of UrologyJan 5, 2021, 12:00:00 AMEditorial Comment Volume 205Issue 3March 2021Page: 709-717Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordscomparative effectiveness researchimmune checkpoint inhibitorsurotheliumnivolumabAcknowledgmentResearch reported in this publication utilized the Cancer Biostatistics Shared Resource at Huntsman Cancer Institute at the University of Utah.MetricsAuthor Information Umang Swami Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah Equal study contribution. More articles by this author Benjamin Haaland Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah Department of Population Health Sciences, University of Utah, Salt Lake City, Utah Equal study contribution. Financial interest and/or other relationship with Astra Zeneca, Prometics Life Sciences, Value Analytics Labs and National Kidney Foundation. More articles by this author Adam Kessel Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah More articles by this author Roberto Nussenzveig Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah Financial interest and/or other relationship with Tempus. More articles by this author Benjamin Louis Maughan Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah Financial interest and/or other relationship with Janssen, Astellas, Bristol-Myers Squibb, Clovis, Tempus, Merck, Bayer, Exelixis, Bayer Oncology, Peloton Therapeutics and Bavarian-Nordic. More articles by this author John Esther Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah More articles by this author Deepika Sirohi Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, Utah More articles by this author Sumanta K. Pal Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California Financial interest and/or other relationship with Genentech, Aveo, Eisai, Roche, Pfizer, Novartis, Exelixis, Ipsen, BMS and Astellas. More articles by this author Petros Grivas Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington ¶Correspondence: Clinical Research Division, Fred Hutchinson Cancer Research Center, 825 Eastlake Ave. E, Seattle, Washington 98109-1024 (FAX: 206-606-2042; E-mail Address: [email protected] and Financial interest and/or other relationship with AstraZeneca, Bayer, Biocept, Bristol-Myers Squibb, Clovis Oncology, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech, Genzyme, GlaxoSmithKline, Heron Therapeutics, Janssen, Merck, Mirati Therapeutics, Pfizer, Roche, Seattle Genetics, QED Therapeutics, Oncogenex, Bavarian Nordic, Immunomedics and Debiopharm. More articles by this author Neeraj Agarwal Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah ¶Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Dr., Suite 5726, Salt Lake City, Utah 84112 telephone: 801‐213‐5658; E-mail Address: [email protected] Financial interest and/or other relationship with Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Janssen, Merck, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics, Bavarian Nordic, Calithera, Celldex, Exelixis, Glaxo Smith Kline, Janssen, Merck, New Link Genetics, Novartis, Prometheus, Rexahn, Roche, Sanofi, Takeda and Tracon. More articles by this author Expand All Supported by the National Cancer Institute of the National Institutes of Health under Award No. P30CA042014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. 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