Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2
Hope S Rugo, Richard S Finn, Karen Gelmon, Anil A Joy, Nadia Harbeck, Aurelio Castrellon, Hirofumi Mukai, Janice M Walshe, Ave Mori, Eric Gauthier, Dongrui Ray Lu, Eustratios Bananis, Miguel Martin, Véronique Diéras, Hope S Rugo, Richard S Finn, Karen Gelmon, Anil A Joy, Nadia Harbeck, Aurelio Castrellon, Hirofumi Mukai, Janice M Walshe, Ave Mori, Eric Gauthier, Dongrui Ray Lu, Eustratios Bananis, Miguel Martin, Véronique Diéras
Abstract
Background: In PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017).
Patients and methods: Postmenopausal patients untreated for ER+/HER2- ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm.
Results: In the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016).
Conclusions: Palbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER+/HER2- ABC regardless of achieving RECIST-defined OR. Pfizer; ClinicalTrials.gov: NCT01740427.
Keywords: Cyclin-dependent kinase; Inhibitor; Metastatic breast cancer; Tumor response.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed