Dataset Information

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

ABSTRACT:

Purpose

Metastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue.

Methods

A search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study were assessed according to the selection criteria and were divided into two groups: ACI versus no ACI. Outcomes were toxicity, objective response, 1-, 3- and 5-year survival. Risk ratio (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by value of I(2) or P.

Results

4 studies (469 patients) were included. Most of ACI-related adverse reactions were grade 1 or 2 and reversible. ACI provided significant benefit in terms of objective response (RR?=?1.65; 95% CI, 1.15 to 2.38; P?=?0.007, I(2)?=?49%), 1-year survival (RR?=?1.30; 95% CI, 1.12 to 1.52; P?=?0.0008, I(2)?=?0%), 3-year survival (RR?=?2.76; 95% CI, 1.85 to 4.14; P<0.00001, I(2)?=?46%) and 5-year survival (RR?=?2.42; 95% CI, 1.21 to 4.83; P?=?0.01, I(2)?=?28%).

Conclusions

ACI may be a safe and effective treatment for improving objective response, 1-, 3- and 5-year survival in patients with mRCC. Besides, five obstacles for ACI, including high degree of personalization, unsuitable WHO/RECIST response criteria, inadequate identification of tumor-associated antigens (TAAs), lack of effective combination treatments and less attention paid to the quality of ACI products, should be overcome during the successful development of more potent ACI for cancer in the future.

SUBMITTER: Tang X

PROVIDER: S-EPMC3647060 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Tang Xiaoyi X Liu Ting T Zang Xuefeng X Liu Hao H Wang Danhong D Chen Hu H Zhang Bin B

PloS one 20130507 5

<h4>Purpose</h4>Metastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue.<h4>Methods</h4>A search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study w ...[more]

PMID: 23667530

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Project description:ObjectiveTo compare the effectiveness and safety of treatments for advanced or metastatic renal cell carcinoma (amRCC) after treatment with vascular endothelial growth factor (VEGF)-targeted treatment.DesignSystematic review and network meta-analysis of randomised controlled trials (RCTs) and comparative observational studies. MEDLINE, EMBASE and Cochrane Library were searched up to January 2018.ParticipantsPeople with amRCC requiring treatment after VEGF-targeted treatment.InterventionsAxitinib, cabozantinib, everolimus, lenvatinib with everolimus, nivolumab, sorafenib and best supportive care (BSC).OutcomesPrimary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were objective response rate (ORR), adverse events, and health-related quality of life (HRQoL).ResultsTwelve studies were included (n=5144): five RCTs and seven observational studies. Lenvatinib with everolimus significantly increased OS and PFS over everolimus (HR 0.61, 95% Credible Interval [95%CrI]: 0.36 to 0.96 and 0.47, 95%CrI: 0.26 to 0.77, respectively) as did cabozantinib (HR 0.66, 95%CrI: 0.53 to 0.82 and 0.51, 95%CrI: 0.41 to 0.63, respectively). This remained the case when observational evidence was included. Nivolumab also significantly improved OS versus everolimus (HR 0.74, 95%CrI: 0.57 to 0.93). OS sensitivity analysis, including observational studies, indicates everolimus being more effective than axitinib and sorafenib. However, inconsistency was identified in the OS sensitivity analysis. PFS sensitivity analysis suggests axitinib is more effective than everolimus, which may be more effective than sorafenib. The results for ORR supported the OS and PFS analyses. Nivolumab is associated with fewer grade 3 or grade 4 adverse events than lenvatinib with everolimus or cabozantinib. HRQoL could not be analysed due to differences in tools used.ConclusionsLenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axitinib and sorafenib.Prospero registration numberCRD42017071540.

Project description:BackgroundRandomized controlled trials (RCTs) have stringent inclusion criteria and may not fully represent patients seen in everyday clinical practice. Real-world data (RWD) can provide supportive evidence for the effectiveness of medical interventions in more heterogeneous populations than RCTs. Sunitinib is a widely used first-line treatment for patients with metastatic renal cell carcinoma (mRCC).ObjectiveThis is the first comprehensive meta-analysis to evaluate the efficacy of sunitinib using the novel approach of combining RCTs and RWD.MethodsRCTs and RWD studies published between 2000 and 2017 were identified from PubMed, Ovid, MEDLINE, and EMBASE. Eligible studies contained a cohort of ??50 adult patients with mRCC receiving first-line sunitinib treatment. The meta-analysis combined RWD and RCT treatment groups, adjusting for data type (RCT or RWD). Recorded outcomes were median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR). Publication bias was assessed via review of funnel plots for each outcome measure. A random effects model to account for study heterogeneity was applied to each endpoint. Sensitivity analyses evaluated the robustness of the overall estimates.ResultsOf the 3611 studies identified through medical database searches, 22 (15 RWD studies, 7 RCTs) met eligibility criteria and were analyzed. mPFS (18 studies), mOS (19 studies), and ORR (15 studies) were reported for aggregate measures based on 4815, 5321, and 4183 patients, respectively. Reported mPFS (RWD, 7.5-11.0 months; RCTs, 5.6-15.1 months) and ORR data (RWD, 14.0-34.6%; RCTs, 18.8-46.9%) were consistent with the overall confidence estimates (95% confidence interval [CI]) of 9.3 (8.6-10.2) months and 27.9% (24.2-32.0), respectively. Reported mOS showed greater variation in RWD (6.8-33.2 months) compared with RCTs (21.8-31.5 months), with an overall confidence estimate (95% CI) of 23.0 (19.2-27.6) months. Inspection of funnel plots and sensitivity analyses indicated that there was no publication bias for any efficacy endpoint. Sensitivity analyses showed no evidence of lack of robustness for mPFS, mOS, or ORR. Interpretation of these results is limited by differences in trial design, cohort characteristics, and missing data.ConclusionsThis novel, comprehensive meta-analysis validates sunitinib as an effective first-line treatment for patients with mRCC in both RCTs and everyday clinical practice. The methodology provides a framework for future analyses combining data from RCTs and RWD.

Dataset Information

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Purpose

Methods

Results

Conclusions

Publications

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Similar Datasets

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