Breast Cancer Coverage from Every Angle

PEARL Trial in Metastatic Breast Cancer: Palbociclib Plus Endocrine Therapy Versus Capecitabine

By: Noelle Cutter, PhD
Posted: Tuesday, March 9, 2021

To better understand the efficacy of palbociclib plus endocrine therapy compared with that of chemotherapy alone, the phase III PEARL trial was conducted. The findings of this study, published in Annals of Oncology, suggest that the palbociclib combination does not show improved progression-free survival compared with chemotherapy alone in hormone receptor–positive HER2-negative, metastatic breast cancer who were resistant to aromatase inhibitors. However, a better safety profile and improved quality of life with the palbociclib combination therapy were reported by Miguel Martin, MD, PhD, of Gregorio Marañón Institute in Madrid, and colleagues.

The design of the study included two cohorts based on the presence of wild-type estrogen receptor-1 (ESR1) or mutant-ESR1. Cohort 1 consisted of 296 patients who either received palbociclib with exemestane or capecitabine; cohort 2 consisted of 305 patients who received palbociclib plus fulvestrant or capecitabine. 

The investigators reported that palbociclib plus endocrine therapy was not superior to capecitabine in both cohort 2 (median progression-free survival of 7.5 vs. 10.0 months) and in patients with wild-type ESR1 disease (8.0 vs. 10.6 months). However, palbociclib plus endocrine therapy showed a better safety profile and improved quality of life in patients compared with chemotherapy. The most common grade 3 or 4 adverse events with the palbociclib combination were neutropenia, hand/foot syndrome, and diarrhea.

Given the limited efficacy of palbociclib and endocrine therapy in this patient population, the investigators believe their study findings “indirectly suggest that palbociclib combinations are less effective in pretreated metastatic breast cancer patients and should be used earlier in the treatment timeline, while capecitabine can be left for later lines.”

Disclosure: For full disclosures of the study authors, visit

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