dc.contributor.author | Johnston, S | |
dc.contributor.author | Puhalla, S | |
dc.contributor.author | Wheatley, D | |
dc.contributor.author | Ring, A | |
dc.contributor.author | Barry, P | |
dc.contributor.author | Holcombe, C | |
dc.contributor.author | Boileau, JF | |
dc.contributor.author | Provencher, L | |
dc.contributor.author | Robidoux, A | |
dc.contributor.author | Rimawi, M | |
dc.contributor.author | McIntosh, SA | |
dc.contributor.author | Shalaby, I | |
dc.contributor.author | Stein, RC | |
dc.contributor.author | Thirlwell, M | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Morden, J | |
dc.contributor.author | Snowdon, C | |
dc.contributor.author | Perry, S | |
dc.contributor.author | Cornman, C | |
dc.contributor.author | Batten, LM | |
dc.contributor.author | Jeffs, LK | |
dc.contributor.author | Dodson, A | |
dc.contributor.author | Martins, V | |
dc.contributor.author | Modi, A | |
dc.contributor.author | Osborne, CK | |
dc.contributor.author | Pogue-Geile, KL | |
dc.contributor.author | Cheang, MCU | |
dc.contributor.author | Wolmark, N | |
dc.contributor.author | Julian, TB | |
dc.contributor.author | Fisher, K | |
dc.contributor.author | MacKenzie, M | |
dc.contributor.author | Wilcox, M | |
dc.contributor.author | Huang Bartlett, C | |
dc.contributor.author | Koehler, M | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Jacobs, SA | |
dc.date.accessioned | 2018-12-17T11:37:42Z | |
dc.date.issued | 2019-01-20 | |
dc.identifier.citation | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (3), pp. 178 - 189 | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2976 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/jco.18.01624 | |
dc.description.abstract | PURPOSE: CDK4/6 inhibitors are used to treat estrogen receptor (ER)-positive metastatic breast cancer (BC) in combination with endocrine therapy. PALLET is a phase II randomized trial that evaluated the effects of combination palbociclib plus letrozole as neoadjuvant therapy. PATIENTS AND METHODS: Postmenopausal women with ER-positive primary BC and tumors greater than or equal to 2.0 cm were randomly assigned 3:2:2:2 to letrozole (2.5 mg/d) for 14 weeks (A); letrozole for 2 weeks, then palbociclib plus letrozole to 14 weeks (B); palbociclib for 2 weeks, then palbociclib plus letrozole to 14 weeks (C); or palbociclib plus letrozole for 14 weeks. Palbociclib 125 mg/d was administered orally on a 21-days-on, 7-days-off schedule. Core-cut biopsies were taken at baseline and 2 and 14 weeks. Coprimary end points for letrozole versus palbociclib plus letrozole groups (A v B + C + D) were change in Ki-67 (protein encoded by the MKI67 gene; immunohistochemistry) between baseline and 14 weeks and clinical response (ordinal and ultrasound) after 14 weeks. Complete cell-cycle arrest was defined as Ki-67 less than or equal to 2.7%. Apoptosis was characterized by cleaved poly (ADP-ribose) polymerase. RESULTS: Three hundred seven patients were recruited. Clinical response was not significantly different between palbociclib plus letrozole and letrozole groups ( P = .20; complete response + partial response, 54.3% v 49.5%), and progressive disease was 3.2% versus 5.4%, respectively. Median log-fold change in Ki-67 was greater with palbociclib plus letrozole compared with letrozole (-4.1 v -2.2; P < .001) in the 190 evaluable patients (61.9%), corresponding to a geometric mean change of -97.4% versus -88.5%. More patients on palbociclib plus letrozole achieved complete cell-cycle arrest (90% v 59%; P < .001). Median log-fold change (suppression) of cleaved poly (ADP-ribose) polymerase was greater with palbociclib plus letrozole versus letrozole (-0.80 v -0.42; P < .001). More patients had grade 3 or greater toxicity on palbociclib plus letrozole (49.8% v 17.0%; P < .001) mainly because of asymptomatic neutropenia. CONCLUSION: Adding palbociclib to letrozole significantly enhanced the suppression of malignant cell proliferation (Ki-67) in primary ER-positive BC, but did not increase the clinical response rate over 14 weeks, which was possibly related to a concurrent reduction in apoptosis. | |
dc.format | Print-Electronic | |
dc.format.extent | 178 - 189 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER SOC CLINICAL ONCOLOGY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Piperazines | |
dc.subject | Pyridines | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Receptors, Estrogen | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Aromatase Inhibitors | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Chemotherapy, Adjuvant | |
dc.subject | Neoadjuvant Therapy | |
dc.subject | Drug Administration Schedule | |
dc.subject | Postmenopause | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Letrozole | |
dc.title | Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-11-01 | |
rioxxterms.versionofrecord | 10.1200/jco.18.01624 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
pubs.issue | 3 | |
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/Endocrine Therapy Resistance | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
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/Endocrine Therapy Resistance | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 37 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Endocrine Therapy Resistance | |
icr.researchteam | Clinical Trials & Statistics Unit | |
icr.researchteam | Genomic Analysis – Clinical Trials | |
icr.researchteam | Endocrinology | |
dc.contributor.icrauthor | Dolling, David | |
dc.contributor.icrauthor | Snowdon, Claire | |
dc.contributor.icrauthor | Cheang, Chon | |
dc.contributor.icrauthor | Bliss, Judith | |