PCN74 COMPARISON OF THE COST-EFFECTIVENESS OF ZOLEDRONIC ACID THERAPY FOR RENAL CELL CARCINOMA (RCC) PATIENTS WITH BONE METASTASES IN FRENCH, GERMAN, AND THE UK POPULATIONS

Abstract Purpose Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results Twenty-seven patients were included in the study. The median age was 65 (range, 50–84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0–34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2–89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

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Skeletal Complications in Patients with Bone Metastases from Renal Cell Carcinoma and Therapeutic Benefits of Zoledronic Acid

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-040030 ◽

2004 ◽

Vol 10 (18) ◽

pp. 6397S-6403S ◽

Cited By ~ 73

Author(s):

Allan Lipton ◽

Alejandro Colombo-Berra ◽

Ronald M. Bukowski ◽

Lee Rosen ◽

Ming Zheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Zoledronic Acid ◽

Bone Metastases ◽

Cell Carcinoma ◽

Renal Cell ◽

Therapeutic Benefits ◽

Skeletal Complications

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Potential synergistic effects of bisphosphonates with sorafenib on renal cell carcinoma with bone metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.496 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 496-496

Author(s):

Ye Ding-Wei ◽

Zhang Hai-Lang

Keyword(s):

Renal Cell Carcinoma ◽

Zoledronic Acid ◽

Bone Metastases ◽

Cell Carcinoma ◽

Renal Cell ◽

Independent Predictor ◽

Study Groups ◽

Significant Difference ◽

Group 2 ◽

Group 1

496 Background: We evaluated the role of bisphosphonates in conjunction with sorafenib in improving progression-free survival (PFS) and overall survival (OS) in bone metastatic renal cell carcinoma (mRCC) patients. Methods: A total of 81 sorafenib-treated patients were retrospectively divided into 3 groups at our single study center: Group 1 (n=26, sorafenib single agent); Group 2 (n=26, sorafenib plus oral Bonefos); Group 3 (n=29, sorafenib plus intravenous zoledronic acid). Alkaline phosphatase (ALP) before and 12 weeks after treatment were evaluated as prognostic factor for PFS and OS. Results: The majority of the patients were males (67.9%) with mean age of 57.2 ± 11.2 years. Baseline demographic characteristics were similar across the 3 study groups, and the known prognostic factors were balanced across the cohort. There was no significant difference observed in the objective response between the 3 study groups (Group 1 vs. 2 vs. 3; p=0.659); partial remission (8% vs. 8% vs. 10%), stable disease (65% vs. 80% vs. 66%), progressive disease (27% vs. 12% vs. 24%). Median PFS was significantly higher in Group 2 vs 1 vs 2 (18.7 vs. 6.7 vs. 10.5 months; p=0.024). Median OS was 16.8, 22.1, and 20.7 months; p=0.052 in Group 1, 2 and 3, respectively. Multivariate analysis demonstrated that bisphosphonate use (hazard ratio [HR]=0.36, p=0.006), Memorial Sloan Kettering Cancer Center (MSKCC) score (HR=4.10, p<0.001), non-clear cell subtype (HR=1.26, p=0.039), and elevated ALP after 12 weeks’ treatment (HR=3.53, p<0.001) were associated with PFS. MSKCC score (HR=5.24, p<0.001), elevated ALP after 12 weeks’ treatment (HR=4.71, p<0.001), and metastatic organs (HR=1.93, p=0.008) were associated with OS. Bisphosphonates use was not an independent predictor of OS (HR=0.55, p=0.160). Conclusions: Bisphosphonates administered with sorafenib could synergistically improve PFS and OS in RCC with bone metastases, with the benefit of being more efficacious and safer than intravenous zoledronic acid. Elevated ALP following the treatment could be an independent predictor for both PFS and OS in bone mRCC.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16067 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16067-e16067

Author(s):

Kenji Omae ◽

Yasushi Tsujimoto ◽

Michitaka Honda ◽

Tsunenori Kondo ◽

Yasunobu Hashimoto ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Zoledronic Acid ◽

Bone Metastases ◽

Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Efficacy And Safety

e16067 Background: Bone-modifying agents (BMA) have been well-demonstrated to be effective for preventing and inhibiting skeletal-related events (SRE) in patients with bone metastases of breast or prostate cancer. However, the role of BMA treatment has not yet been clearly defined in patients with bone metastases of renal cell carcinoma (RCC). We, therefore, conducted a systematic review and meta-analysis to evaluate the efficacy and safety of BMA in patients with bone metastases of RCC. Methods: Literature search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify randomized controlled trials of BMA for the treatment of bone metastases in RCC patients. The primary outcomes were SRE and serious adverse events (AEs). Hazard ratios (HRs) were calculated with a random effects model. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. This review was prospectively registered on PROSPERO (No. CRD42016032742). Results: Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or non-zoledronic acid showed that zoledronic acid reduced the SRE risk by 68% (HR 0.32; 95% confidence interval (CI) 0.19–0.55; P < 0.0001). The quality of evidence was moderate. No serious osteonecrosis was reported in both studies. The incidence of serious AEs was identical (80%) on both treatment arms in one study and not reported in the other study. In the remaining study, which compared denosumab with zoledronic acid, analyses of the individual patient data shared through Amgen showed a favorable trend for denosumab in terms of SRE (HR 0.71; 95% CI 0.43–1.17) and serious AEs (risk ratio 0.86; 95% CI 0.68–1.08), but this trend did not reach statistical significance. Conclusions: The moderate-quality evidence indicates that zoledronic acid significantly reduces the risk of SRE among patients with bone metastases of RCC.

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