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

This analysis examined the clinical outcomes of patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in PALOMA-2 who achieved and did not achieve an objective response. Palbociclib plus letrozole provided a significant clinical benefit by prolonging median progression-free survival versus placebo plus letrozole regardless of whether patients achieved an objective response. Background: In PALOMA-2, palbociclibletrozole 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. (C) 2019 The Authors. Published by Elsevier Inc.