As reported at the 2021 San Antonio Breast Cancer Symposium (Abstract GS1-07) and simultaneously in the Journal of Clinical Oncology by Michael Gnant, MD, and colleagues, the final analysis of the phase III PALLAS trial has shown no invasive disease–free survival benefit with the addition of adjuvant palbociclib to endocrine therapy in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer.

As stated by the investigators, “Palbociclib is a CDK4/6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for HR-positive breast cancer has not been confirmed.”

Michael Gnant, MD

Study Details

In the open-label trial, 5,761 patients from sites in 21 countries were randomly assigned between September 2015 and November 2018 to receive standard adjuvant endocrine therapy (tamoxifen and an aromatase inhibitor, with or without ovarian function suppression) for ≥ 5 years with (n = 2,884) or without (n = 2,877) 2 years of palbociclib at 125 mg once daily on days 1 to 21 of 28-day cycles. The primary endpoint was invasive disease–free survival.

Invasive Disease–Free Survival

Median follow-up at the final protocol-defined analysis was 31 months (interquartile range = 24.5–37.3 months). Invasive disease–free survival events occurred in 253 patients (8.8%) in the palbociclib group vs 263 (9.1%) in the control group, with 4-year invasive disease–free survival rates of 84.2% vs 84.5% (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.81–1.14, P = .65). Findings were similar in subgroup analyses according to stage, grade, receipt of neoadjuvant or adjuvant chemotherapy, and age.  

No significant differences were found in 4-year rates of invasive breast cancer–free survival (85.4% vs 86.0%, HR = 0.99, 95% CI = 0.82–1.19), distant recurrence–free survival (86.2% vs 87.8%, HR = 1.05, 95% CI = 0.87–1.28), locoregional recurrence–free survival (96.8% vs 95.4%, HR = 0.84, 95% CI = 0.57–1.23), or overall survival (93.8% vs 95.2%, HR = 1.32, 95% CI = 0.98–1.78).

Adverse Events

Adverse events of any grade occurred in 99.5% of patients in the palbociclib group and 89.7% of the control group, with the most common in the palbociclib group being neutropenia (83.5% vs 5.0%), leukopenia (55.1% vs 7.5%), and fatigue (41.0% vs 19.3%). Other adverse events more common in the palbociclib group were upper respiratory tract infection (29.5% vs 16.6%), anemia (23.5% vs 5.5%), thrombocytopenia (21.8% vs 1.7%), and alopecia (18.0% vs 5.1%). Grade ≥ 3 adverse events occurred in 73.8% vs 15.5% of patients, with the most common in the palbociclib group being neutropenia (62.0% vs < 1%) and leukopenia (30.4% vs < 1%). Serious adverse events occurred in 13.0% vs 7.9% of patients. No treatment-related deaths were reported.  

The investigators concluded, “At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early HR-positive breast cancer.”

Dr. Gnant, of the Comprehensive Cancer Center, Medical University of Vienna, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit ascopubs.org.