April 2021: First results of the randomized phase III PenelopeB trial

About one third of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor demonstrating efficacy in the metastatic setting. The randomized phase III PenelopeB study evaluated the addition of the CDK4/6 inhibitor palbociclib to endocrine therapy as post-neoadjuvant treatment for HR-positive/HER2-negative, breast cancer patients with high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+) after neoadjuvant chemotherapy. Patients received either palbociclib 125 mg orally once daily for 21 days followed by 1 week off treatment for a total duration of 13 4-week cycles or matching placebo in addition to standard adjuvant endocrine therapy at the discretion of the investigator given for at least 5 years. The primary endpoint was invasive disease-free survival (iDFS). Secondary endpoints included iDFS excluding second primary invasive nonbreast cancers, distant disease-free survival, overall survival, locoregional relapse-free interval, safety, and compliance. After a median follow-up of 43 months the addition of 1 year palbociclib to standard adjuvant endocrine therapy did not significantly improve iDFS. The estimated 3-year iDFS was 81.2% (95%CI 77.8%-84.1%) with palbociclib and 77.7% (95%CI 74.1%-80.9%) with placebo. No new safety signals were observed. PenelopeB is the first study showing mature iDFS results on a CDK4/6 inhibitor as part of (post-neo)adjuvant therapy in early breast cancer. Further translational research and subgroup analyses are ongoing.

Loibl S, Marmé F, Martin M, et al. Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial. J Clin Oncol. 2021 Apr 1:JCO2003639. doi: 10.1200/JCO.20.03639.

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