As reported in The Lancet Oncology by Erica L. Mayer, MD, and colleagues, the second interim analysis of the phase III PALLAS trial showed no improvement in invasive disease–free survival with the addition of adjuvant palbociclib to ongoing endocrine therapy in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer.

The addition of palbociclib to endocrine therapy has previously been shown to improve progression-free survival in patients with HR-positive, HER2-negative metastatic breast cancer.

Erica L. Mayer, MD

Study Details

The open-label trial included 5,760 patients with stage II to III disease from sites in 21 countries. Patients were randomly assigned between September 2015 and November 2018 to receive 2 years of palbociclib at 125 mg once daily on days 1 to 21 of a 28-day cycle with ongoing standard provider’s or patient’s choice of adjuvant endocrine therapy (n = 2,883) or endocrine therapy alone (control group, n = 2,877). Endocrine therapy consisted of tamoxifen or an aromatase inhibitor, with or without a luteinizing hormone-releasing hormone agonist. The primary endpoint was invasive disease­–free survival in the intention-to-treat population.

Invasive Disease–Free Survival

The second preplanned interim analysis was performed after 67% of the total number of expected invasive disease–free survival events had been reached in January 2020. At a median follow-up of 23.7 months, 3-year invasive disease-free survival was 88.2% (95% confidence interval [CI] = 85.2%–90.6%) in the palbociclib group vs 88.5% (95% CI = 85.8%–90.7%) in the control group (hazard ratio [HR] = 0.93, 95% CI = 0.76–1.15, P = .51).

Since the comparison crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. No difference between groups was observed in distant recurrence–free survival, with 3-year rates of 89.3% vs 90.7% (HR = 1.00, 95% CI = 0.79–1.27, P = .9997). No clinicopathologic subgroups appeared to benefit from the addition of palbociclib to endocrine therapy.

Adverse Events

Grade 3–4 adverse events occurred in 72% of patients in the palbociclib group vs 15% of those in the control group, with the most common in the palbociclib group being neutropenia (61% vs < 1%), leukopenia (30% vs < 1%), lymphopenia (3% vs < 1%), and fatigue (2% vs < 1%). Serious adverse events occurred in 12.4% vs 7.6% of patients, with the most common in the palbociclib group being tissue infection (1.7%) and upper respiratory tract infection (0.8%). No treatment-related deaths were reported.

The investigators concluded, “At the planned second interim analysis, [the] addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease–free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing.”

Dr. Mayer, of Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.

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