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 to Letrozole: Analysis from PALOMA-2

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 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 (mDOR), 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 194/444 (44%) and 77/222 (35%) patients in the palbociclib and placebo arms, respectively (odds ratio=1.5 [95% CI=1.0–2.1]; P=0.0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%–50%, 28–31%) and no prior endocrine therapy (55%, 35–37%). Rates of palbociclib dose reduction due to AEs were similar regardless of OR (41%, 38%). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. Median PFS was significantly prolonged with palbociclib+letrozole versus placebo+letrozole in patients with measurable disease in both OR (37.2 [95% CI=28.1–not estimable] vs 27.4 [22.2–31.1] months; hazard ratio=0.66 [95% CI=0.47–0.94]; P=0.009) and non-OR groups (10.9 [8.2–11.2] vs 5.6 [5.3–8.3] months; hazard ratio=0.72 [0.54–0.97]; P=0.016). 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;