Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

Gnant, Michael; Pfeiler, Georg; Steger, G.; Egle, Daniel; Greil, Richard; Fitzal, Florian; Wette, Viktor; Balić, Marija; Haslbauer, Ferdinand; Melbinger-Zeinitzer, Elisabeth; Bjelic‐Radisic, Vesna; Jakesz, R.; Marth, Christian; Sevelda, P.; Mlineritsch, Brigitte; Exner, Ruth; Fesl, Christian; Frantal, Sophie; Singer, Christian F.; Breast, Austrian

doi:10.1016/s1470-2045(18)30862-3

Cited by 182 publications

(136 citation statements)

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“…In terms of adverse events, osteonecrosis in the jaw was reported significantly more often in the denosumab arm in the D-CARE trial as compared to placebo [31]. The ABCSG-18 trial, using a lower dose of denosumab, did not observe any differences in the occurrence of osteonecrosis between the use of adjuvant denosumab and placebo [32]. Further, the Medicines and Healthcare products Regulatory Agency recently cautioned that denosumab has been associated with an increased incidence of new primary malignancies (1-year cumulative incidence 1.1%) [33].…”

Section: Discussionmentioning

confidence: 90%

“…More recently, the effect of the anti-receptor activator of nuclear factor kappa-B ligand denosumab on breast cancer survival was investigated, showing contrasting results [31,32]. The ABCSG-18 trial observed a clear advantage of denosumab (60 mg 6-monthly) on disease-free survival (DFS) (HR 0.82, p = 0.026) in a study population of postmenopausal women using AIs, who were generally at a low risk of recurrence (25% received prior chemotherapy) [32]. In the denosumab group, DFS was 80.6% at 8 years of follow-up, compared with 77.5% in the placebo group.…”

Section: Discussionmentioning

confidence: 99%

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Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Hellemond

Smorenburg

Peer³

et al. 2020

Breast Cancer Res Treat

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Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS.Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.Keywords Breast cancer · Tamoxifen · Aromatase inhibitor · Bone health · Osteoporosis · Bisphosphonates · Survival · Bone metastases · Distant recurrence-free survival Part of these results were presented at the poster session of the 2018 San Antonio Breast Cancer Symposium, abstract number 810.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Hellemond

Smorenburg

Peer³

et al. 2020

Breast Cancer Res Treat

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“…Aside from bisphosphonates, another important question is whether the use of adjuvant denosumab, a RANKL inhibitor that also modifies the bone microenvironment, prevents or delays disease progression from early‐stage breast cancer. The phase III ABSCG‐18 and the D‐CARE adjuvant trials, together encompassing more than 7900 patients, were presented at the 2018 ASCO annual meeting . Both the trials found conflicting results; the ABSCG‐18 trial showed that adjuvant denosumab increased disease‐free survival in postmenopausal women (HR = 0.823, 95% CI 0.69‐0.98), whereas the D‐CARE trial found no benefit of the drug in early breast cancer patients receiving optimal loco‐regional and standard of care systemic adjuvant therapy .…”

Section: Other Optionsmentioning

confidence: 99%

“…The phase III ABSCG‐18 and the D‐CARE adjuvant trials, together encompassing more than 7900 patients, were presented at the 2018 ASCO annual meeting . Both the trials found conflicting results; the ABSCG‐18 trial showed that adjuvant denosumab increased disease‐free survival in postmenopausal women (HR = 0.823, 95% CI 0.69‐0.98), whereas the D‐CARE trial found no benefit of the drug in early breast cancer patients receiving optimal loco‐regional and standard of care systemic adjuvant therapy . The dose, administration schedule, and the characteristics of participants with respect to menopausal status were different in these trials.…”

Section: Other Optionsmentioning

confidence: 99%

Adjuvant bisphosphonate therapy in early‐stage breast cancer—Treating the soil to kill the seed

Brufsky

Mathew

2019

Breast J

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Breast J. 2020;26:65-68. wileyonlinelibrary.com/journal/tbj | 65 Abstract Bisphosphonates alter the tumor microenvironment, possibly preventing cancer cell growth in the bone. Analyses of data from numerous clinical trials and a large individual patient-level data meta-analysis have suggested an anti-tumor effect for bisphosphonates in patients with early-stage breast cancer who are postmenopausal.The absolute benefit from the use of bisphosphonates on breast cancer-related mortality reduction mirrors that seen with the use of anthracycline-based chemotherapy versus a first-generation chemotherapy regimen (CMF). In this review, we discuss the evidence base for the use of adjuvant bisphosphonates in early-stage breast cancer and provide recommendations for clinical use. K E Y W O R D S bisphosphonate, breast cancer, early-stage, therapy How to cite this article: Brufsky A, Mathew A. Adjuvant bisphosphonate therapy in early-stage breast cancer-Treating the soil to kill the seed. Breast J. 2020;26: 65-68. https ://doi.

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“…Randomized clinical trials of adjuvant denosumab treatment in breast cancer are underway, and preliminary findings have so far shown improved disease-free survival. 6 It will remain a challenge to personalize treatment for ER-negative/PR-cancer considering that this subtype now constitutes only 1% of all breast cancers.…”

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confidence: 99%

Single Hormone Receptor–Positive Breast Cancer—Signal or Noise?

Giannakeas

2020

JAMA Netw Open

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Canonical predictors for the prognosis of breast cancer include estrogen receptor (ER), progesterone receptor (PR), and ERBB2 (formerly HER2) receptor. In most cases, positive ER status is auspicious, but there are exceptions (young women, black women, and BRCA2 mutation carriers). The simplest designation, hormone receptor-positive cancers, includes tumors that express ER and/or PR (hormone receptor-negative cancers express neither). A complementary classification scheme

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Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

Cited by 182 publications

References 38 publications

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Adjuvant bisphosphonate therapy in early‐stage breast cancer—Treating the soil to kill the seed

Single Hormone Receptor–Positive Breast Cancer—Signal or Noise?

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