Adjuvant immunotherapy in high-risk muscle invasive urothelial carcinoma: A systematic review and meta-analysis of randomized clinical trials.

Autor: Oscar-Thompson L; Department of Urology, Houston Methodist Hospital, Houston, TX., Riveros C; Department of Urology, Houston Methodist Hospital, Houston, TX., Sonpavde G; Department of Hematology and Oncology, Genitourinary Oncology Program, AdventHealth Cancer Institute, Orlando, FL., Apolo AB; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Lalani AA; Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada., Wallis CJD; Division of Urology and Surgical Oncology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Urology, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Mount Sinai Hospital, Toronto, Ontario, Canada., Satkunasivam R; Department of Urology, Houston Methodist Hospital, Houston, TX. Electronic address: raj.satkunasivam@gmail.com.
Jazyk: angličtina
Zdroj: Urologic oncology [Urol Oncol] 2024 Sep 16. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1016/j.urolonc.2024.08.003
Abstrakt: Despite surgical resection, many patients with muscle invasive urothelial carcinoma (MIUC) experience recurrence. Adjuvant immune checkpoint inhibition (ICI) following radical resection in patients with MIUC demonstrates disparate outcomes among phase III randomized controlled trials (RCTs). Our objective was to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with MIUC and evaluate the overall safety profile of ICIs in this setting. The protocol was registered with PROSPERO, CRD42022352587. We searched MEDLINE, Embase, CENTRAL, and relevant conference proceedings from inception up to January 29, 2024. Only phase III RCTs comparing adjuvant ICI versus placebo/observation were selected. Study screening and selection, along with data extraction was performed in duplicate according to a predefined registered protocol. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used. Quality assessment was performed using the Cochrane risk-of-bias (RoB 2) tool for randomized trials. The primary and secondary endpoints were DFS and serious adverse events, respectively. All outcomes were analyzed using random-effects meta-analysis owing to inter-study heterogeneity. Sensitivity and subgroup analyses were performed to identify potential sources of heterogeneity. A priori defined subgroups of interest included positive program death-ligand 1 (PD-L1) expression, previous use of neoadjuvant chemotherapy (NAC), primary tumor origin, pathologic lymph node status, and baseline Eastern Cooperative Oncology Group performance status. Pooled results across the 3 RCTs (2,220 patients) demonstrated significantly improved DFS for patients treated with ICI in the intention-to-treat cohorts (HR 0.76, 95% CI 0.65-0.90). There was considerable clinical and statistical heterogeneity (I 2  = 44%) due to differences in inclusion criteria and interventions. Overall, there was a low risk of bias among the RCTs. Regarding subgroup analyses, there was significant benefit among patients with negative PD-L1 expression (HR 0.76, 95% CI 0.64-0.90), those who received prior NAC (HR 0.69, 95% CI 0.52-0.91), and patients with lower tract (HR 0.71, 95% CI 0.55-0.92) but not upper tract disease (HR 1.21, 95% CI 0.87-1.68). This pooled analysis of DFS and safety provides support for ICI utilization in the setting of high-risk resected MIUC.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 1. Oscar-Thompson, Riveros, Apolo: None. 2. Sonpavde: a. Advisory Board: BMS, Genentech, EMD Serono, Merck, Astrazeneca, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV, Vial, Syapse, Tempus, Ellipses Pharma, PrecisCa, Primum b. Consultant/Scientific Advisory Board (SAB): Suba Therapeutics, Syapse, Servier, Merck, Syncorp c. Research Support to institution: Sanofi, Astrazeneca, Gilead, Helsinn, Lucence, BMS, EMD Serono, Jazz Therapeutics d. Speaker: BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, OLE Forum (Mexico), Seagen, Gilead, Natera, Exelixis, Janssen, Bayer, Aveo e. Data safety monitoring committee honorarium: Mereo f. Employment: Spouse employed by Myriad. 3. Lalani: a. Honoraria - Astellas Pharma; Bayer; Bristol-Myers Squibb; Eisai; Ipsen; Merck; Novartis; Pfizer; Roche/Genentech b. Consulting or Advisory Role - Abbvie; Astellas Pharma; Bayer; Bristol-Myers Squibb; Eisai; Ipsen; Janssen; Merck; Pfizer; Roche/Genentech c. Research Funding - BioCanRx (Inst); Bristol-Myers Squibb (Inst); EMD Serono (Inst); Ipsen (Inst); Novartis (Inst); Roche (Inst). 4. Wallis a. Consulting Fees: Janssen Oncology, Nanostics Inc, Precision Point Specialty LLC, SESEN Bio b. Honoraria/Travel: AbbVie, Astellas, Astra Zeneca, Bayer, EMD Serono, Haymarket Media, c. Healing and Cancer Foundation, Knight Therapeutics, Merck, Science & Medicine Canada, d. TerSera Canada, Tolmar Pharmaceuticals Canada e. Research Funding: Knight Therapeutics, Tolmar Pharmaceuticals, Bayer 5. Satkunasivam a. Research Funding or Support to Institution: Pfizer, BMS, Anchiano Therapeutics, QED Therapeutics, Merck, CoImmune, UroGen, enGene, Photocure, Janssen b. Consulting: Pfizer (2022-2023), Intuitive Surgical (Proctor, 2019; 2023), GNE/Roche (2017) c. Stock: None d. Honoraria/Travel: None. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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