Palbociclib with Adjuvant Endocrine Therapy in Early Breast Cancer (PALLAS): Interim Analysis of a Multicenter, Open-Label, Randomized, Phase 3 Study
Background: The role of palbociclib in the metastatic setting for hormone receptor positive HER-2/neu negative invasive breast cancer is well-established. The role of CDK 4 6 inhibitors, and in particular palbociclib, in the adjuvant setting, has yet to be determined. In the PALLAS clinical trial, investigators attempted to answer this question.
Methods: PALLAS is an ongoing open label, multicenter, randomized phase 3 clinical trial that is enrolled patients across 406 centers in 21 countries around the world, with stage II and stage III hormone receptor positive HER-2/neu negative invasive breast cancer. Patients needed to be accrued within 12 months of initial diagnosis. Patients have been at least 18 years of age, with good performance status. Patients underwent a one-to-one randomization and permitted blocks of random size (4 or 6), and were stratified by age, anatomic stage, chemotherapy exposure as well as geographic region. The patients were treated with 2 years of palbociclib, 125 mg daily, 3 weeks on, 1 week off. Patients were also treated with adjuvant endocrine therapy, either provider choice or patient choice. Options included tamoxifen or an aromatase inhibitor, with or without a luteinizing hormone releasing hormone agonist. The comparator arm was endocrine therapy only without a CT correlate for 6 inhibitor. Invasive disease-free survival and the intention to treat population was the primary endpoint. This publication, presents the results from the second preplanned interim analysis which was triggered on January 9, 2020. At that point, 67% of the total number of expected invasive disease-free survival events had occurred.
Results: 5760 patients were randomly assigned to both arms. At the time of the second plan interim analysis, with a medium follow-up of 23.7 months, 170 patients out of 2883 assigned to palbociclib plus endocrine therapy and 181 patients out of 2877 assigned to endocrine therapy alone, had invasive disease-free survival events. 3-year invasive disease-free survival was 88.2% for the treatment arm versus 88.5% for the endocrine therapy alone arm. The hazard ratio for this was 0.93, with a 95% confidence interval of0.76-1.15, p=0.51. When the prespecified futility boundary was crossed the independent data monitoring committee recommended discontinuation of palbociclib. The most common grade 3 or 4 adverse event was neutropenia, seen in 61.3% of patients. It only occurred in 0.3% of patients undergoing endocrine therapy. Leukopenia was seen in 30.2% and 0.1% respectively. Serious adverse events were seen in 12.4% versus 7.6%. No treatment related that were reported.
Conclusion: The authors concluded that at the planned second interim analysis, the addition of palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared to adjuvant endocrine therapy alone. The authors do not recommend utilizing palbociclib in the adjuvant setting for stage II stage III hormone receptor positive HER-2/neu negative invasive breast cancer.