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Comparative Study
. 2025 Aug:82:104502.
doi: 10.1016/j.breast.2025.104502. Epub 2025 May 15.

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors

Roberta Scafetta  1 , Marco Donato  1 , Carla Gullotta  1 , Alessandra Guarino  1 , Cristina Fiore  2 , Luisana Sisca  1 , Elena Speziale  1 , Raffaella Troiano  1 , Simone Foderaro  3 , Valentina Ricozzi  1 , Michele Iuliani  4 , Sonia Simonetti  1 , Silvia Cavaliere  3 , Alessio Cortellini  5 , Andrea Botticelli  6 , Simone Scagnoli  6 , Simona Pisegna  6 , Carmen Criscitiello  7 , Rebecca Pedersini  8 , Caterina Sposetti  9 , Elisa Tiberi  10 , Giuliana D'Auria  11 , Matteo Vergati  11 , Marco Mazzotta  11 , Roberta Caputo  12 , Annarita Verrazzo  12 , Maria Grazia Rossino  13 , Federica Domati  14 , Claudia Piombino  14 , Francesca Sofia Di Lisa  15 , Lorena Filomeno  15 , Teresa Arcuri  15 , Federica Puce  16 , Federica Riva  17 , Michela Palleschi  18 , Marianna Sirico  18 , Marta Piras  19 , Luigia Stefania Stucci  20 , Delia De Lisi  21 , Paolo Orsaria  22 , Edy Ippolito  23 , Sara Ramella  23 , Luca Visani  24 , Niccolò Bertini  24 , Ilaria Bonaparte  24 , Stefania Gori  25 , Luigi Rossi  26 , Icro Meattini  27 , Barbara Tagliaferri  16 , Orazio Caffo  21 , Ilaria Portarena  28 , Azzurra Irelli  29 , Elisabetta Cretella  30 , Camillo Porta  20 , Giampaolo Bianchini  31 , Agnese Fabbri  32 , Ugo De Giorgi  18 , Patrizia Vici  15 , Angela Toss  14 , Ornella Garrone  13 , Michelino De Laurentiis  12 , Federica Villa  33 , Rossana Berardi  10 , Mauro Minelli  34 , Claudio Vernieri  9 , Giuseppe Curigliano  7 , Bruno Vincenzi  5 , Giuseppe Tonini  5 , Daniele Santini  6 , Francesco Pantano  5
Affiliations
Comparative Study

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors

Roberta Scafetta et al. Breast. 2025 Aug.

Abstract

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies. In the unadjusted cohort, ZA was associated with a longer time to first SRE compared to DMAB (HR = 0.77, 95 % CI: 0.61-0.98, p = 0.031). Similar results were obtained in both the PSM (HR = 0.69, 95 % CI: 0.52-0.92, p = 0.011) and IPTW cohorts (HR = 0.74, 95 % CI: 0.63-0.87, p < 0.001), with ZA-treated patients showing an extended time to first SRE compared to those treated with DMAB. No differences in PFS and OS were observed between the two cohorts.

Keywords: Bone metastasis; Breast cancer; CDK4/6 inhibitors; Denosumab; Zoledronic acid.

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Conflict of interest statement

Declaration of competing interest The Authors declare no Competing Financial or Non-Financial Interests related to this study.

Figures

Fig. 1
Fig. 1
(A) Kaplan-Meier estimates of time to first SRE in “unadjusted” cohort. (B) Cox regression multivariate analysis.
Fig. 2
Fig. 2
Kaplan-Meier estimates of time to first SRE in “PSM” (A) and “IPTW” (B) cohorts.
Fig. 3
Fig. 3
Frequency (%) of SRE type in “unadjusted” (A), “PSM” (B) and “IPTW” (C) cohorts.
Fig. 4
Fig. 4
Kaplan-Meier estimates of PFS in “unadjusted” (A), “PSM” (B) and “IPTW” (C) cohorts.
Fig. 5
Fig. 5
Kaplan-Meier estimates of OS in “unadjusted” (A), “PSM” (B) and “IPTW” (C) cohorts.
See this image and copyright information in PMC

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