Association between prior nephrectomy and efficacy of immune checkpoint inhibitor therapy in metastatic renal cell carcinoma - A systematic review and meta-analysis

Author(s):  
Raj Satkunasivam ◽  
Jonathan CA Guzman ◽  
Zachary Klaassen ◽  
Mary E Hall ◽  
Amy N Luckenbaugh ◽  
...  
2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 318-318
Author(s):  
Chiara Ciccarese ◽  
Roberto Iacovelli ◽  
Emilio Bria ◽  
Giovanni Schinzari ◽  
Ernesto Rossi ◽  
...  

318 Background: Combinations of a PD-1/PD-L1 immune checkpoint inhibitor (ICI) with a VEGFR-TKI as front-line/treatment-naïve therapy significantly improve the outcome of metastatic renal cell carcinoma (mRCC) patients. The benefit of these combinations is well evident in IMDC intermediate- and poor-risk population, while it is unclear in the subgroup of mRCC patients with favorable prognosis. We performed a meta-analysis with the aim to evaluate whether the addition of ICIs to VEGFR-TKIs is able to improve the outcome compared to VEGFR-TKIs alone in mRCC patients with favorable IMDC prognosis. Methods: This meta-analysis searched MEDLINE/PubMed, the Cochrane Library and ASCO Meeting abstracts for phase II or III randomized clinical trials (RCTs) testing the combination of VEGFR-TKI+ICI in mRCC. Data extraction was conducted according to the PRISMA statement. The hazard ratios (HRs) for PFS and OS with the relative 95% CIs were extracted from each study. Summary HRs was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. Results: Three RCTs were selected for the final analysis, with a total of 605 patients (306 treated with VEGFR-TKI+ICI combinations and 299 who received sunitinib in the control arms). The combination of VEGFR-TKI+ICI improved PFS compared to sunitinib, with a 30% reduction of the risk of progression (fixed-effect, HR=0.70; p = 0.003). However, VEGFR-TKI+ICI combinations did not significantly prolong OS (fixed-effect; HR = 0.94; 95% CI 0.62–1.43; p = 0.77). Conclusions: Our analysis demonstrates a PFS benefit without an OS advantage for VEGFR-TKI+ICI combinations as first-line therapy for mRCC patients with favourable prognosis according to IMDC. Longer follow-up is required to definitely confirm the best therapy for treatment-naïve mRCC patients with favorable prognosis. [Table: see text]


Author(s):  
Hiroki Ishihara ◽  
Toshio Takagi ◽  
Tsunenori Kondo ◽  
Hironori Fukuda ◽  
Hidekazu Tachibana ◽  
...  

Abstract Objective Studies assessing outcome improvements over a long period according to systemic therapy strategies for metastatic renal cell carcinoma using real-world data, including the results of the recent era of immune checkpoint inhibitors, are limited. Herein, we retrospectively evaluated patients who were diagnosed with metastatic renal cell carcinoma over a 40-year span. Methods Patients were classified into four groups based on when their metastases were diagnosed as follows: (i) the pre-cytokine era (1980–1986), (ii) the cytokine era (1987–2007), (iii) the molecular-targeted therapy (mTT) era (2008 to August 2016) and (iv) the immune checkpoint inhibitor era (September 2016 to 2018). The immune checkpoint inhibitor era consisted of second- or later-line nivolumab. Overall survival from the diagnoses of metastases was evaluated. Results In total, 576 patients were evaluated, including 22 (3.82%), 231 (40.1%), 253 (43.9%) and 70 (12.2%) patients from the pre-cytokine, cytokine, molecular-targeted therapy and immune checkpoint inhibitor eras, respectively. The overall survival significantly improved with each successive era (median: 13.1 vs. 24.5 vs. 44.4 months vs. not reached in pre-cytokine vs. cytokine vs. molecular-targeted therapy vs. immune checkpoint inhibitor eras, P < 0.0001). The implementation of molecular-targeted therapy improved overall survival compared with that of cytokine (cytokine vs. molecular-targeted therapy eras, P < 0.0001). Multivariate analysis demonstrated that the era was an independent factor for overall survival (P < 0.0001), together with histopathological type; metastasis status (i.e. synchronous or metachronous); systemic therapy status (i.e. absence or presence) and bone, liver or lymph node metastasis status (all, P < 0.05). Conclusion This retrospective study of real-world data indicated that metastatic renal cell carcinoma outcomes improved with successive systemic therapy paradigms.


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