Palbociclib with adjuvant endocrine therapy in early breast cancer: 5-year follow-up analysis of the global multicenter, open-label, randomized phase III PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13).

[BACKGROUND] In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS).

[PATIENTS AND METHODS] PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS.

[RESULTS] The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [95% confidence interval (CI) 82.7% to 85.6%] in the palbociclib plus ET arm and 82.4% (95% CI 80.8% to 83.9%) in the ET-alone arm [hazard ratio (HR) 0.88, 95% CI 0.77-1.01, log-rank P = 0.0614]. No significant iDFS benefit of palbociclib was observed in any subgroup, including analyses by anatomic stage, T-stage, N-stage, tumor grade, prior (neo)adjuvant chemotherapy, age, or clinical risk. The 5-year OS was 92.6% (95% CI 91.5% to 93.6%) in the palbociclib plus ET arm and 93.2% (95% CI 92.1% to 94.1%) in the ET-alone arm (HR 1.09, 95% CI 0.89-1.33, log-rank P = 0.4051). More patients in the ET-alone arm (65.7%) than in the palbociclib plus ET arm (33.0%) received cyclin-dependent kinase 4/6 inhibitors after recurrence. Conversely, more patients in the palbociclib plus ET arm (52.5%) than in the ET-alone arm (41.0%) received chemotherapy after recurrence.

[CONCLUSIONS] In conclusion, 5-year follow-up from the PALLAS trial confirms initially reported results. These long-term findings will provide investigators with important benchmarks for clinical outcomes in the contemporary management of HR-positive/HER2-negative breast cancer, and may be further used to guide adjuvant therapy for patients with high-risk early-stage HR-positive/HER2-negative breast cancer.