Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial

Gnant, Michael; Mlineritsch, Brigitte; Stoeger, Herbert; Luschin-Ebengreuth, G.; Heck, Dietmar; Menzel, Christian; Jakesz, R.; Seifert, Michael; Hubalek, Michael; Pristauz, Gunda; Bauernhofer, Thomas; Eidtmann, Holger; Eiermann, W.; Steger, Guenther G.; Kwasny, Werner; Dubsky, Peter; Hochreiner, Gerhard; Forsthuber, Ernst-Pius; Fesl, Christian; Greil, Richard

doi:10.1016/s1470-2045(11)70122-x

Cited by 430 publications

(336 citation statements)

References 38 publications

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“…However, the majority of bisphosphonate studies only evaluated treatment for 2 years or less, with approximately 11%–36% of patients completing the studies and considered eligible for further treatment (Morgan et al., 2010; Rosen et al., 2003; Saad et al., 2004; Theriault et al., 1999). Few prospective and retrospective studies have reported on the efficacy and safety of bisphosphonate treatment beyond 2 years (Crawford et al., 2009; Dearnaley, Mason, Parmar, Sanders, & Sydes, 2009; Gnant et al., 2011; La Verde et al., 2008; Morgan et al., 2012). This small, prospective, observational study helps to confirm the safety and ongoing efficacy of monthly treatment with ZOL for 2–3 years in patients with malignant disease involving bone, in the era of new safety guidelines.…”

Section: Discussionmentioning

confidence: 99%

“…These results are consistent with the low incidence of ONJ in patients continuing with monthly ZOL in recent long‐term studies (≤5%) and in studies implementing the new safety guidelines (≤6.7%) (Dimopoulos et al., 2009; Gnant et al., 2011; Morgan et al., 2012; Ripamonti et al., 2009). Among patients with MM who received ZOL treatment before preventive dental measures, in one study ( n = 38), the incidence of ONJ (albeit not adjudicated) was 26% (Dimopoulos et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Compared with the large bisphosphonate studies, which had renal AE rates of 2.3% in CRPC ( N = 643) to 10.7% in BrCa and MM ( N = 1,648) (Rosen et al., 2003; Saad et al., 2002), the renal AE incidence rate of 11% in this study with primarily BrCa and MM patients was reasonable. However, in other long‐term studies, the incidence of renal effects ranged from none in patients with BrCa ( N = 1,803) to 7% in patients with MM experiencing acute renal failure ( N = 1,960) (Gnant et al., 2011; Morgan et al., 2012). Differing patient baseline characteristics and definitions for renal endpoints may account for the wide variations reported for renal impairment.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, the strength of ZOL efficacy may be diluted. In other long‐term studies, SRE rates were not an endpoint; therefore, there is no basis for a comparison of continuing efficacy (Dearnaley et al., 2009; Gnant et al., 2011; Morgan et al., 2012). In the large bisphosphonate study in patients with BrCa and MM evaluating treatment for the first 2 years, the SRE rates were approximately 1 event per year for ZOL in the overall population and in patients with BrCa (Rosen et al., 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Zoledronic acid (ZOL) is a well‐recognised supportive treatment for patients with bone disease associated with haematological malignancies such as multiple myeloma (MM), as well as in non‐haematological malignancies such as metastatic breast and prostate cancers (Gnant et al., 2011; Kohno et al., 2005; Morgan et al., 2010; Rosen et al., 2003; Saad et al., 2004). …”

Section: Introductionmentioning

confidence: 99%

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Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Khalafallah

Slancar²,

Cosolo³

et al. 2017

Eur J Cancer Care

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Malignant bone disease can cause significant morbidity. Monthly zoledronic acid (ZOL) reduces skeletal complications; however, limited data are available regarding long‐term safety. We aimed to assess efficacy and safety of ZOL beyond 1 year of treatment. We prospectively evaluated 73 patients; breast cancer (n = 29), castrate‐resistant prostate cancer (n = 13), multiple myeloma (n = 31) from 2006 to 2008 in 19 cancer centres. All patients were diagnosed with bone disease and had completed 1–2 years of monthly ZOL (4 mg) and received a further 1–2 years of therapy following contemporary guidelines for managing risks of osteonecrosis of the jaw (ONJ) and renal toxicity. Overall rates of skeletal‐related events (SREs), renal impairment and ONJ were assessed. Over the additional 1 year of treatment, only 5.5% (n = 4) of patients developed a new SRE. The overall Kaplan–Meier estimate for SRE incidence after 48 weeks on study was 6.75% (95 CI: 2.5–17.3). Although 51% of patients reported serious adverse events, only two cases were suspected as ZOL related. No patients had confirmed ONJ. The observed incidence of new renal impairment was 11% (none due to ZOL). Our study confirms the benefit over risk of continuing monthly ZOL for at least 2 years in patients with advanced cancer involving bone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Khalafallah

Slancar²,

Cosolo³

et al. 2017

Eur J Cancer Care

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Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer

et al. 2014

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IMPORTANCE Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials.OBJECTIVE To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double-blind, placebo-controlled trials. DESIGN, SETTING, AND PARTICIPANTSThe Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test. INTERVENTION Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT). MAIN OUTCOMES AND MEASURESHazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group. RESULTSThere was no significant difference in the rate of breast cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8% (n = 29) in the placebo group and 0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when the data from FIT and HORIZON-PFT were pooled (HR, 1.20 [95% CI, 0.89-1.63]). CONCLUSIONS AND RELEVANCEThese 2 randomized clinical trials do not support the findings from observational research. Contrary to the results from observational studies, we found that 3 to 4 years of bisphosphonate treatment did not decrease the risk of invasive postmenopausal breast cancer.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00049829(HORIZON-PFT)

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Adjuvant Zoledronate Therapy for Women With Breast Cancer—Effective Treatment or Fool’s Gold?

2021

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Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial

Cited by 430 publications

References 38 publications

Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone (LoTESS): A multicentre prospective phase 4 study

Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer

Adjuvant Zoledronate Therapy for Women With Breast Cancer—Effective Treatment or Fool’s Gold?

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