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dc.contributor.authorVerma, Sen_US
dc.contributor.authorBartlett, CHen_US
dc.contributor.authorSchnell, Pen_US
dc.contributor.authorDeMichele, AMen_US
dc.contributor.authorLoi, Sen_US
dc.contributor.authorRo, Jen_US
dc.contributor.authorColleoni, Men_US
dc.contributor.authorIwata, Hen_US
dc.contributor.authorHarbeck, Nen_US
dc.contributor.authorCristofanilli, Men_US
dc.contributor.authorZhang, Ken_US
dc.contributor.authorThiele, Aen_US
dc.contributor.authorTurner, NCen_US
dc.contributor.authorRugo, HSen_US
dc.date.accessioned2016-09-28T11:10:01Z
dc.date.issued2016-07en_US
dc.identifier.citationThe oncologist, 2016en_US
dc.identifier.issn1083-7159en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/129
dc.identifier.eissn1549-490Xen_US
dc.description.abstractPalbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit.Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data.A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients.Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135.Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib-related neutropenia differs in its clinical time course, patterns, and consequences from those seen with chemotherapy. Neutropenia can be effectively managed by a dose reduction, interruption, or cycle delay without compromising efficacy. A significant efficacy gain and a favorable safety profile support the consideration of incorporating palbociclib into the routine management of HR-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.titlePalbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).en_US
dc.typeJournal Article
dcterms.dateAccepted2016-05-10en_US
rioxxterms.licenseref.startdate2016-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfThe oncologisten_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorTurner, Nicholasen_US


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