dc.contributor.author | Verma, S | |
dc.contributor.author | Bartlett, CH | |
dc.contributor.author | Schnell, P | |
dc.contributor.author | DeMichele, AM | |
dc.contributor.author | Loi, S | |
dc.contributor.author | Ro, J | |
dc.contributor.author | Colleoni, M | |
dc.contributor.author | Iwata, H | |
dc.contributor.author | Harbeck, N | |
dc.contributor.author | Cristofanilli, M | |
dc.contributor.author | Zhang, K | |
dc.contributor.author | Thiele, A | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Rugo, HS | |
dc.date.accessioned | 2016-09-28T11:10:01Z | |
dc.date.issued | 2016-10-01 | |
dc.identifier.citation | The oncologist, 2016, 21 (10), pp. 1165 - 1175 | |
dc.identifier.issn | 1083-7159 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/129 | |
dc.identifier.eissn | 1549-490X | |
dc.identifier.doi | 10.1634/theoncologist.2016-0097 | |
dc.description.abstract | BACKGROUND: Palbociclib 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. IMPLICATIONS FOR PRACTICE: 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1165 - 1175 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Piperazines | |
dc.subject | Pyridines | |
dc.subject | Estradiol | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Receptors, Estrogen | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Double-Blind Method | |
dc.subject | Female | |
dc.subject | Fulvestrant | |
dc.title | Palbociclib 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). | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-05-10 | |
rioxxterms.versionofrecord | 10.1634/theoncologist.2016-0097 | |
rioxxterms.licenseref.startdate | 2016-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The oncologist | |
pubs.issue | 10 | |
pubs.notes | Not known | |
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.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.publication-status | Published | |
pubs.volume | 21 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Turner, Nicholas | |