Final Analysis of PALLAS Shows No Benefit With Palbociclib Plus Endocrine Therapy in Early Breast Cancer

Female patient on hospital bed.
Female patient on hospital bed.
Palbociclib added to adjuvant endocrine therapy failed to improve iDFS.

The addition of palbociclib to adjuvant endocrine therapy did not improve survival when compared with endocrine therapy alone among patients with early-stage, hormone receptor (HR)-positive and HER2-negative breast cancer, according to the final analysis of the phase 3 PALLAS trial presented at the 2021 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in the Journal of Clinical Oncology.

“Benefits previously observed in the metastatic setting with palbociclib did not translate into the earlier curative adjuvant setting,” Michael Gnant, MD, of the Medical University of Vienna in Austria, and lead author of the study, said.

The open-label, phase 3 PALLAS trial randomly assigned 5761 patients with stage II to III HR-positive, HER-negative breast cancer to adjuvant treatment with 5 years of endocrine therapy (aromatase inhibitor or tamoxifen with or without a luteinizing hormone-releasing hormone) with or without 2 years of palbociclib. The primary endpoint was invasive disease-free survival (iDFS) and secondary endpoints included distant recurrence-free survival (DRFS), locoregional recurrence-free survival (LRRFS), overall survival (OS), and safety.

Active treatment with palbociclib was stopped in May 2020 due to futility and the remaining patients who were receiving palbociclib were transferred to follow-up. This presentation was the final analysis of the trial data with a median follow-up of 31 months.

Palbociclib added to adjuvant endocrine therapy failed to improve iDFS, with a 4-year rate of 84.2% compared with 84.5% with endocrine therapy alone (hazard ratio [HR], 0.96; 95% CI, 0.81-1.14; P =.65).

All secondary efficacy outcomes were also similar between the treatment arms.

Palbociclib was discontinued early by 42% of patients, with 28.2% of discontinuations related to adverse events (AEs). However, there was no significant benefit with the addition of palbociclib among patients who completed or nearly completed treatment, suggesting that the negative result of the PALLAS trial was not due to insufficient exposure to the drug, Dr Gnant said.

The most common grade 3 to 4 AE with palbociclib was neutropenia, which occurred among 61.9% of patients compared with 0.4% of patients in the endocrine therapy only arm.

Dr Gnant concluded that “we will continue long-term follow-up and we will continue to [work to] better understanding the biology of luminal breast cancer.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Gnant M, Dueck AC, Frantal S, et al. Adjuvant palbociclib in HR+/HER2- early breast cancer: Final results from 5,760 patients in the randomized phase III PALLAS trial. Presented at SABCS 2021; December 7 to 10, 2021; San Antonio, TX. Abstract GS1-07.

This article originally appeared on MPR