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

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...

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Main Authors: Roberta Scafetta, Marco Donato, Carla Gullotta, Alessandra Guarino, Cristina Fiore, Luisana Sisca, Elena Speziale, Raffaella Troiano, Simone Foderaro, Valentina Ricozzi, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Alessio Cortellini, Andrea Botticelli, Simone Scagnoli, Simona Pisegna, Carmen Criscitiello, Rebecca Pedersini, Caterina Sposetti, Elisa Tiberi, Giuliana D'Auria, Matteo Vergati, Marco Mazzotta, Roberta Caputo, Annarita Verrazzo, Maria Grazia Rossino, Federica Domati, Claudia Piombino, Francesca Sofia Di Lisa, Lorena Filomeno, Teresa Arcuri, Federica Puce, Federica Riva, Michela Palleschi, Marianna Sirico, Marta Piras, Luigia Stefania Stucci, Delia De Lisi, Paolo Orsaria, Edy Ippolito, Sara Ramella, Luca Visani, Niccolò Bertini, Ilaria Bonaparte, Stefania Gori, Luigi Rossi, Icro Meattini, Barbara Tagliaferri, Orazio Caffo, Ilaria Portarena, Azzurra Irelli, Elisabetta Cretella, Camillo Porta, Giampaolo Bianchini, Agnese Fabbri, Ugo De Giorgi, Patrizia Vici, Angela Toss, Ornella Garrone, Michelino De Laurentiis, Federica Villa, Rossana Berardi, Mauro Minelli, Claudio Vernieri, Giuseppe Curigliano, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini, Francesco Pantano
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Language:English
Published: Elsevier 2025-08-01
Series:Breast
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Online Access:http://www.sciencedirect.com/science/article/pii/S0960977625005193
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author Roberta Scafetta
Marco Donato
Carla Gullotta
Alessandra Guarino
Cristina Fiore
Luisana Sisca
Elena Speziale
Raffaella Troiano
Simone Foderaro
Valentina Ricozzi
Michele Iuliani
Sonia Simonetti
Silvia Cavaliere
Alessio Cortellini
Andrea Botticelli
Simone Scagnoli
Simona Pisegna
Carmen Criscitiello
Rebecca Pedersini
Caterina Sposetti
Elisa Tiberi
Giuliana D'Auria
Matteo Vergati
Marco Mazzotta
Roberta Caputo
Annarita Verrazzo
Maria Grazia Rossino
Federica Domati
Claudia Piombino
Francesca Sofia Di Lisa
Lorena Filomeno
Teresa Arcuri
Federica Puce
Federica Riva
Michela Palleschi
Marianna Sirico
Marta Piras
Luigia Stefania Stucci
Delia De Lisi
Paolo Orsaria
Edy Ippolito
Sara Ramella
Luca Visani
Niccolò Bertini
Ilaria Bonaparte
Stefania Gori
Luigi Rossi
Icro Meattini
Barbara Tagliaferri
Orazio Caffo
Ilaria Portarena
Azzurra Irelli
Elisabetta Cretella
Camillo Porta
Giampaolo Bianchini
Agnese Fabbri
Ugo De Giorgi
Patrizia Vici
Angela Toss
Ornella Garrone
Michelino De Laurentiis
Federica Villa
Rossana Berardi
Mauro Minelli
Claudio Vernieri
Giuseppe Curigliano
Bruno Vincenzi
Giuseppe Tonini
Daniele Santini
Francesco Pantano
author_facet Roberta Scafetta
Marco Donato
Carla Gullotta
Alessandra Guarino
Cristina Fiore
Luisana Sisca
Elena Speziale
Raffaella Troiano
Simone Foderaro
Valentina Ricozzi
Michele Iuliani
Sonia Simonetti
Silvia Cavaliere
Alessio Cortellini
Andrea Botticelli
Simone Scagnoli
Simona Pisegna
Carmen Criscitiello
Rebecca Pedersini
Caterina Sposetti
Elisa Tiberi
Giuliana D'Auria
Matteo Vergati
Marco Mazzotta
Roberta Caputo
Annarita Verrazzo
Maria Grazia Rossino
Federica Domati
Claudia Piombino
Francesca Sofia Di Lisa
Lorena Filomeno
Teresa Arcuri
Federica Puce
Federica Riva
Michela Palleschi
Marianna Sirico
Marta Piras
Luigia Stefania Stucci
Delia De Lisi
Paolo Orsaria
Edy Ippolito
Sara Ramella
Luca Visani
Niccolò Bertini
Ilaria Bonaparte
Stefania Gori
Luigi Rossi
Icro Meattini
Barbara Tagliaferri
Orazio Caffo
Ilaria Portarena
Azzurra Irelli
Elisabetta Cretella
Camillo Porta
Giampaolo Bianchini
Agnese Fabbri
Ugo De Giorgi
Patrizia Vici
Angela Toss
Ornella Garrone
Michelino De Laurentiis
Federica Villa
Rossana Berardi
Mauro Minelli
Claudio Vernieri
Giuseppe Curigliano
Bruno Vincenzi
Giuseppe Tonini
Daniele Santini
Francesco Pantano
author_sort Roberta Scafetta
collection DOAJ
description 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.
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spelling doaj-art-9a87e6c9100c42e48395076cc56c416b2025-08-20T03:50:58ZengElsevierBreast1532-30802025-08-018210450210.1016/j.breast.2025.104502Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitorsRoberta Scafetta0Marco Donato1Carla Gullotta2Alessandra Guarino3Cristina Fiore4Luisana Sisca5Elena Speziale6Raffaella Troiano7Simone Foderaro8Valentina Ricozzi9Michele Iuliani10Sonia Simonetti11Silvia Cavaliere12Alessio Cortellini13Andrea Botticelli14Simone Scagnoli15Simona Pisegna16Carmen Criscitiello17Rebecca Pedersini18Caterina Sposetti19Elisa Tiberi20Giuliana D'Auria21Matteo Vergati22Marco Mazzotta23Roberta Caputo24Annarita Verrazzo25Maria Grazia Rossino26Federica Domati27Claudia Piombino28Francesca Sofia Di Lisa29Lorena Filomeno30Teresa Arcuri31Federica Puce32Federica Riva33Michela Palleschi34Marianna Sirico35Marta Piras36Luigia Stefania Stucci37Delia De Lisi38Paolo Orsaria39Edy Ippolito40Sara Ramella41Luca Visani42Niccolò Bertini43Ilaria Bonaparte44Stefania Gori45Luigi Rossi46Icro Meattini47Barbara Tagliaferri48Orazio Caffo49Ilaria Portarena50Azzurra Irelli51Elisabetta Cretella52Camillo Porta53Giampaolo Bianchini54Agnese Fabbri55Ugo De Giorgi56Patrizia Vici57Angela Toss58Ornella Garrone59Michelino De Laurentiis60Federica Villa61Rossana Berardi62Mauro Minelli63Claudio Vernieri64Giuseppe Curigliano65Bruno Vincenzi66Giuseppe Tonini67Daniele Santini68Francesco Pantano69Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Medical Oncology Unit, Central Hospital of Belcolle, Department of Oncology and Hematology, Strada Sammartinese snc, 01100, Viterbo, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyDepartment of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Corresponding author.Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, ItalyDepartment of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyDip. Scienze e Biotecnologie Medico-chirurgiche, Policlinico Umberto I, “Sapienza” University of Rome, Rome, ItalyDip. Scienze e Biotecnologie Medico-chirurgiche, Policlinico Umberto I, “Sapienza” University of Rome, Rome, ItalyDip. Scienze e Biotecnologie Medico-chirurgiche, Policlinico Umberto I, “Sapienza” University of Rome, Rome, ItalyDivision of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milano, Milano, ItalyMedical Oncology Department, ASST Spedali Civili of Brescia, Brescia, ItalyDepartment of Oncology and Hemato-Oncology, University of Milano, Milano, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Medical Oncology, Università Politecnica Delle Marche, AOU delle Marche, Ancona, ItalyDepartment of Medical Oncology, Medical Oncology Unit, Sandro Pertini Hospital, Rome, ItalyDepartment of Medical Oncology, Medical Oncology Unit, Sandro Pertini Hospital, Rome, ItalyDepartment of Medical Oncology, Medical Oncology Unit, Sandro Pertini Hospital, Rome, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, ItalyMedical Oncology Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, ItalyDepartment of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyDepartment of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyUOSD Sperimentazioni di fase IV - IRCCS Istituto Nazionale Tumori Regina Elena, Via Elio Chianesi 53, 00144, Roma, ItalyUOSD Sperimentazioni di fase IV - IRCCS Istituto Nazionale Tumori Regina Elena, Via Elio Chianesi 53, 00144, Roma, ItalyUOSD Sperimentazioni di fase IV - IRCCS Istituto Nazionale Tumori Regina Elena, Via Elio Chianesi 53, 00144, Roma, ItalyMedical Oncology Unit, ICS Maugeri IRCCS, Pavia, ItalyDepartment of Clinical and Molecular Medicine, ''La Sapienza'' University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, ItalyDivision of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Bari, ItalyMedical Oncology Unit, Santa Chiara Hospital, APSS Trento, ItalyDepartment of Breast Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDepartment of Radiation Oncology (Medicine and Surgery), Università Campus Bio-Medico di Roma, Rome, Italy; Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDepartment of Radiation Oncology (Medicine and Surgery), Università Campus Bio-Medico di Roma, Rome, Italy; Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyRadiation Oncology Unit &amp; Breast Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, ItalyRadiation Oncology Unit &amp; Breast Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, ItalyRadiation Oncology Unit &amp; Breast Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, ItalyMedical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR), ItalyUOC of Oncology - ASL Latina - Distretto 1, University of Rome “Sapienza”, Formia, ItalyRadiation Oncology Unit &amp; Breast Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy; Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, ItalyMedical Oncology Unit, ICS Maugeri IRCCS, Pavia, ItalyMedical Oncology Unit, Santa Chiara Hospital, APSS Trento, ItalyDepartment of Oncology, Policlinico Tor Vergata University, Rome, ItalyMedical Oncology Unit, Department of Oncology, “Giuseppe Mazzini” Hospital, AUSL 04 Teramo, 64100, Teramo, ItalyMedical Oncology Unit, Ospedale di Bolzano, Bolzano, ItalyDivision of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Bari, ItalyDepartment of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Università Vita-Salute San Raffaele, Milan, ItalyMedical Oncology Unit, Central Hospital of Belcolle, Department of Oncology and Hematology, Strada Sammartinese snc, 01100, Viterbo, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyUOSD Sperimentazioni di fase IV - IRCCS Istituto Nazionale Tumori Regina Elena, Via Elio Chianesi 53, 00144, Roma, ItalyDepartment of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyMedical Oncology Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, ItalyDepartment of Breast and Thoracic Oncology, Division of Breast Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Pascale, Naples, ItalyMedical Oncology, Oncology Department ASST Lecco, 23900, Lecco, ItalyDepartment of Medical Oncology, Università Politecnica Delle Marche, AOU delle Marche, Ancona, ItalyUOC Oncologia, Azienda Ospedaliera San Giovanni Addolorata, Roma, ItalyDepartment of Oncology and Hemato-Oncology, University of Milano, Milano, Italy; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDivision of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milano, Milano, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyDip. Scienze e Biotecnologie Medico-chirurgiche, Policlinico Umberto I, “Sapienza” University of Rome, Rome, ItalyMedical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Roma, Italy; Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128, Roma, ItalyA 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.http://www.sciencedirect.com/science/article/pii/S0960977625005193Bone metastasisBreast cancerDenosumabZoledronic acidCDK4/6 inhibitors
spellingShingle Roberta Scafetta
Marco Donato
Carla Gullotta
Alessandra Guarino
Cristina Fiore
Luisana Sisca
Elena Speziale
Raffaella Troiano
Simone Foderaro
Valentina Ricozzi
Michele Iuliani
Sonia Simonetti
Silvia Cavaliere
Alessio Cortellini
Andrea Botticelli
Simone Scagnoli
Simona Pisegna
Carmen Criscitiello
Rebecca Pedersini
Caterina Sposetti
Elisa Tiberi
Giuliana D'Auria
Matteo Vergati
Marco Mazzotta
Roberta Caputo
Annarita Verrazzo
Maria Grazia Rossino
Federica Domati
Claudia Piombino
Francesca Sofia Di Lisa
Lorena Filomeno
Teresa Arcuri
Federica Puce
Federica Riva
Michela Palleschi
Marianna Sirico
Marta Piras
Luigia Stefania Stucci
Delia De Lisi
Paolo Orsaria
Edy Ippolito
Sara Ramella
Luca Visani
Niccolò Bertini
Ilaria Bonaparte
Stefania Gori
Luigi Rossi
Icro Meattini
Barbara Tagliaferri
Orazio Caffo
Ilaria Portarena
Azzurra Irelli
Elisabetta Cretella
Camillo Porta
Giampaolo Bianchini
Agnese Fabbri
Ugo De Giorgi
Patrizia Vici
Angela Toss
Ornella Garrone
Michelino De Laurentiis
Federica Villa
Rossana Berardi
Mauro Minelli
Claudio Vernieri
Giuseppe Curigliano
Bruno Vincenzi
Giuseppe Tonini
Daniele Santini
Francesco Pantano
Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
Breast
Bone metastasis
Breast cancer
Denosumab
Zoledronic acid
CDK4/6 inhibitors
title Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
title_full Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
title_fullStr Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
title_full_unstemmed Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
title_short Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors
title_sort comparative analysis of denosumab and zoledronic acid in advanced breast cancer patients receiving cdk4 6 inhibitors
topic Bone metastasis
Breast cancer
Denosumab
Zoledronic acid
CDK4/6 inhibitors
url http://www.sciencedirect.com/science/article/pii/S0960977625005193
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AT federicavilla comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT rossanaberardi comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT maurominelli comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT claudiovernieri comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT giuseppecurigliano comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT brunovincenzi comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT giuseppetonini comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT danielesantini comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors
AT francescopantano comparativeanalysisofdenosumabandzoledronicacidinadvancedbreastcancerpatientsreceivingcdk46inhibitors