Reuben J Broom1, Victoria Hinder2, Katrina Sharples3, Janie Proctor2, Steven Duffey2, Stephanie Pollard2, Peter C C Fong4, Garry Forgeson5, Dean L Harris6, Michael B Jameson7, Anne O'Donnell8, Richard T North9, Sanjeev Deva4, Fritha J Hanning4, Andrew Grey10, Michael P N Findlay2. 1. Regional Cancer and Blood Centre, Auckland City Hospital, Auckland, New Zealand. Electronic address: ReubenB@adhb.govt.nz. 2. Cancer Trials New Zealand, Discipline of Oncology, University of Auckland, New Zealand. 3. Cancer Trials New Zealand, Discipline of Oncology, University of Auckland, New Zealand; Department of Preventative and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. 4. Regional Cancer and Blood Centre, Auckland City Hospital, Auckland, New Zealand. 5. Midcentral Regional Cancer Treatment Service, Palmerston North Hospital, Palmerston North, New Zealand. 6. Oncology Service, Christchurch Hospital, Christchurch, New Zealand. 7. Regional Cancer Centre, Waikato Hospital, Hamilton, New Zealand. 8. Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand. 9. Tauranga Hospital, Tauranga, New Zealand. 10. Department of Medicine, University of Auckland, Auckland, New Zealand.
Abstract
BACKGROUND:Bone metastases from renal cell carcinoma (RCC) are a major cause of morbidity. Post hoc analysis has suggested that bone turnover markers can identify patients at risk of skeletal-related events (SREs) among those receiving zoledronic acid. This study sought to evaluate the effect on bone metastases of everolimus alone compared with everolimus plus zoledronic acid. PATIENTS AND METHODS: Thirty treatment-naive patients with RCC and ≥ 1 bone metastases were randomized 1:1 to everolimus (10 mg daily) versus everolimus plus zoledronic acid (4 mg intravenously 4-weekly). Bone-specific assessments were performed at baseline and at weeks 1, 4, 8, and 12. Treatment was continued on allocated arm until progression per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1). The primary outcome measure was urine N-telopeptide (uNTX) level, with secondary measures of plasma C-telopeptide (CTX), quality of life (Functional Assessment of Cancer Therapy-Bone Pain [FACT-BP], Brief Pain Inventory [BPI]), progression-free survival (PFS), SREs, and safety. RESULTS: After 12 weeks, reduction in mean uNTX and CTX on everolimus plus zoledronic acid relative to everolimus was 68.4% (95% CI, 60.1%-74.9%; P < .0001) and 76.2% (95% CI, 67.3%-82.7%; P < .0001), respectively. There was no evidence of a difference for FACT-BP (P = .5), but evidence was favorable for BPI Severity (P = .05) and BPI Interference (P = .06). Median PFS was 7.5 months (95% CI, 3.4-11.2) on everolimus plus zoledronic acid and 5.4 months (95% CI, 3.2-6.3) on everolimus (P = .009). Median time to first SRE was 9.6 months (95% CI, 4.3-15.5) on everolimus plus zoledronic acid and 5.2 months (95% CI, 1.6-8.2) on everolimus (P = .03). CONCLUSION: In this RCC population, the addition of zoledronic acid to everolimus significantly reduced bone resorption markers and may prolong tumor control.
RCT Entities:
BACKGROUND:Bone metastases from renal cell carcinoma (RCC) are a major cause of morbidity. Post hoc analysis has suggested that bone turnover markers can identify patients at risk of skeletal-related events (SREs) among those receiving zoledronic acid. This study sought to evaluate the effect on bone metastases of everolimus alone compared with everolimus plus zoledronic acid. PATIENTS AND METHODS: Thirty treatment-naive patients with RCC and ≥ 1 bone metastases were randomized 1:1 to everolimus (10 mg daily) versus everolimus plus zoledronic acid (4 mg intravenously 4-weekly). Bone-specific assessments were performed at baseline and at weeks 1, 4, 8, and 12. Treatment was continued on allocated arm until progression per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1). The primary outcome measure was urine N-telopeptide (uNTX) level, with secondary measures of plasma C-telopeptide (CTX), quality of life (Functional Assessment of Cancer Therapy-Bone Pain [FACT-BP], Brief Pain Inventory [BPI]), progression-free survival (PFS), SREs, and safety. RESULTS: After 12 weeks, reduction in mean uNTX and CTX on everolimus plus zoledronic acid relative to everolimus was 68.4% (95% CI, 60.1%-74.9%; P < .0001) and 76.2% (95% CI, 67.3%-82.7%; P < .0001), respectively. There was no evidence of a difference for FACT-BP (P = .5), but evidence was favorable for BPI Severity (P = .05) and BPI Interference (P = .06). Median PFS was 7.5 months (95% CI, 3.4-11.2) on everolimus plus zoledronic acid and 5.4 months (95% CI, 3.2-6.3) on everolimus (P = .009). Median time to first SRE was 9.6 months (95% CI, 4.3-15.5) on everolimus plus zoledronic acid and 5.2 months (95% CI, 1.6-8.2) on everolimus (P = .03). CONCLUSION: In this RCC population, the addition of zoledronic acid to everolimus significantly reduced bone resorption markers and may prolong tumor control.
Authors: Bernard Escudier; Thomas Powles; Robert J Motzer; Thomas Olencki; Osvaldo Arén Frontera; Stephane Oudard; Frederic Rolland; Piotr Tomczak; Daniel Castellano; Leonard J Appleman; Harry Drabkin; Daniel Vaena; Steven Milwee; Jillian Youkstetter; Julie C Lougheed; Sergio Bracarda; Toni K Choueiri Journal: J Clin Oncol Date: 2018-01-08 Impact factor: 44.544
Authors: Fabian Hofmann; Eu Chang Hwang; Thomas Bl Lam; Axel Bex; Yuhong Yuan; Lorenzo So Marconi; Börje Ljungberg Journal: Cochrane Database Syst Rev Date: 2020-10-14
Authors: B Beuselinck; J Jean-Baptiste; G Couchy; S Job; A De Reynies; P Wolter; C Théodore; G Gravis; B Rousseau; L Albiges; S Joniau; V Verkarre; E Lerut; J J Patard; P Schöffski; A Méjean; R Elaidi; S Oudard; J Zucman-Rossi Journal: Br J Cancer Date: 2015-10-13 Impact factor: 7.640