Dataset Information

Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis.

ABSTRACT:

Objective

To determine the comparative efficacy and safety of all available bone-modifying agents (BMAs) for the treatment of bone metastases in patients with advanced renal cell carcinoma (RCC).

Results

Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or no zoledronic acid showed that zoledronic acid reduced the risk of skeletal-related events (SREs) by 68% (pooled hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.19-0.55). The quality of evidence was moderate. The incidence of serious adverse events (AEs) was identical (80%) for both treatment arms in one study and not reported in the other study. In the third study that compared denosumab and zoledronic acid among patients with solid tumors or myeloma, a post-hoc subgroup analysis with individual patient data (155 patients) showed an HR of 0.71 (95% CI: 0.43-1.17) for SREs and a risk ratio of 0.86 (95% CI: 0.68-1.08) for serious AEs for denosumab compared to zoledronic acid.

Materials and methods

We searched the MEDLINE database, Cochrane Library, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov database up to January 2017 without language restriction. Only randomized controlled trials were included. When relevant data were missing, we contacted the investigators of the original study. The Grading of Recommendation Assessment, Development, and Evaluation approach was used to assess the evidence certainty.

Conclusions

Our moderate-quality evidence indicates that zoledronic acid significantly reduces SREs risk among patients with bone metastases of RCC.

SUBMITTER: Omae K

PROVIDER: S-EPMC5620305 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis.

Omae Kenji K Tsujimoto Yasushi Y Honda Michitaka M Kondo Tsunenori T Tanabe Kazunari K Fukuhara Shunichi S Furukawa Toshi A TA

Oncotarget 20170818 40

<h4>Objective</h4>To determine the comparative efficacy and safety of all available bone-modifying agents (BMAs) for the treatment of bone metastases in patients with advanced renal cell carcinoma (RCC).<h4>Results</h4>Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or no zoledronic acid showed that zoledronic acid reduced the risk of skeletal-related events (SREs) by 68% (pooled hazard ratio [HR]: 0.32; 95% confidenc ...[more]

PMID: 28978165

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Project description:BackgroundNivolumab plus ipilimumab (NIVO + IPI) has demonstrated long-term efficacy and safety in patients with previously untreated, advanced renal cell carcinoma (aRCC). Although most phase 3 clinical trials exclude patients with brain metastases, the ongoing, multicohort phase 3b/4 CheckMate 920 trial (ClincalTrials.gov identifier NCT02982954) evaluated the safety and efficacy of NIVO + IPI in a cohort that included patients with aRCC and brain metastases, as reported here.MethodsPatients with previously untreated aRCC and asymptomatic brain metastases received NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × 4 followed by NIVO 480 mg every 4 weeks. The primary end point was the incidence of grade ≥3 immune-mediated adverse events (imAEs) within 100 days of the last dose of study drug. Key secondary end points were progression-free survival and the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (both determined by the investigator). Exploratory end points included overall survival, among others.ResultsAfter a minimum follow-up of 24.5 months (N = 28), no grade 5 imAEs occurred. The most common grade 3 and 4 imAEs were diarrhea/colitis (n = 2; 7%) and hypophysitis, rash, hepatitis, and diabetes mellitus (n = 1 each; 4%). The objective response rate was 32% (95% CI, 14.9%-53.5%) with a median duration of response of 24.0 months; 4 of 8 responders remained without reported progression. Seven patients (25%) had intracranial progression. The median progression-free survival was 9.0 months (95% CI, 2.9-12.0 months), and the median overall survival was not reached (95% CI, 14.1 months to not estimable).ConclusionsIn patients who had previously untreated aRCC and brain metastases-a population with a high unmet medical need that often is underrepresented in clinical trials-the approved regimen of NIVO + IPI followed by NIVO showed encouraging antitumor activity and no new safety signals.

Project description:Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases.We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with ?2, Kaplan-Meier, and log-rank tests.In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively.SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

Dataset Information

Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis.

Objective

Results

Materials and methods

Conclusions

Publications

Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: a systematic review and meta-analysis.

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