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Impact of Tyrosine Kinase Inhibitors (TKIs) Combined With Radiation Therapy for the Management of Brain Metastases From Renal Cell Carcinoma.

ABSTRACT: Background: Targeted therapy has transformed the outcome for patients with metastatic renal cell carcinoma. Their efficacy and safety have also been demonstrated in brain metastatic RCC. Preclinical evidence suggests synergism of radiation and tyrosine kinase inhibitors. Consequently, several studies have compared their efficacy in the treatment of RCC brain metastases to the era of brain management with surgery/radiation only. Objectives: We seek to systematically review and meta-analyze the results of those studies that involved comparative intervention groups of brain management; TKIs, and never used TKIs. Methods and Materials: Online databases (PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov) were searched for comparative studies. Overall survival as the primary outcome of interest, and local brain control, distant control, and adverse events as secondary outcomes of interest were recorded for meta-analysis. Hazard ratios were pooled together using Review Manager 5.3. Fixed effects or random effects model were adopted according to the level of heterogeneity. Subgroup analysis included studies that involved SRS as the local treatment of management. Results: Overall 7 studies (n = 897) were included for meta-analysis. TKI use was associated with better survival (HR 0.60 [0.52, 0.69], p < 0.00001) and local brain control (HR 0.34 [0.11, 0.98], p = 0.05). SRS subgroup also revealed significantly better survival (HR 0.61 [0.44, 0.83], p = 0.002) and local brain control (HR 0.19 [0.08, 0.45], p = 0.0002). Distant brain control (HR 0.95 [0.67, 1.35], p = 0.79) and brain progression free survival were unaffected (HR 0.94 [0.56, 1.56], p = 0.80). Only one study (n = 376) reported significantly greater 12-months cumulative incidence of radiation necrosis with TKI use within 30 days of SRS (10.9 vs. 6.4%, p = 0.04). Conclusions: TKIs use in combination with SRS is safe and effective for treating RCC brain metastases. Larger randomized controlled trials are warranted to validate the results.

SUBMITTER: Khan M

PROVIDER: S-EPMC7390930 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of Tyrosine Kinase Inhibitors (TKIs) Combined With Radiation Therapy for the Management of Brain Metastases From Renal Cell Carcinoma.

Khan Muhammad M Zhao Zhihong Z Arooj Sumbal S Liao Guixiang G

Frontiers in oncology 20200723

<b>Background:</b> Targeted therapy has transformed the outcome for patients with metastatic renal cell carcinoma. Their efficacy and safety have also been demonstrated in brain metastatic RCC. Preclinical evidence suggests synergism of radiation and tyrosine kinase inhibitors. Consequently, several studies have compared their efficacy in the treatment of RCC brain metastases to the era of brain management with surgery/radiation only. <b>Objectives:</b> We seek to systematically review and meta- ...[more]

PMID: 32793497

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Project description:Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC). Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed. Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population. Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.

Dataset Information

Impact of Tyrosine Kinase Inhibitors (TKIs) Combined With Radiation Therapy for the Management of Brain Metastases From Renal Cell Carcinoma.

Publications

Impact of Tyrosine Kinase Inhibitors (TKIs) Combined With Radiation Therapy for the Management of Brain Metastases From Renal Cell Carcinoma.

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