Abstract OT-26-02: Phase III open-label, multicenter, randomized trial of adjuvant palbociclib in combination with endocrine therapy versus endocrine therapy alone for patients with hormone receptor-positive / HER2-negative resected isolated locoregional recurrence of breast cancer - The POLAR Trial
Background: Isolated local or regional recurrence (ILRR) of breast cancer (BC) after mastectomy or lumpectomy indicates a poor prognosis and patients with ILRR hold a substantial risk of developing subsequent distant metastasis. Limited randomized evidence supports the recommendation of systemic treatment for hormone receptor-positive (HR+) lLRR. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, such as palbociclib, have shown activity and safety in the first-line treatment of metastatic HR+/HER2-negative BC. The POLAR hypothesis is based on the results of the CALOR trial (IBCSG Trial 27-02), which showed effectiveness of adjuvant chemotherapy among patients with resected HR-negative ILRR, but not for HR+ ILRR. Considering these findings and compelling evidence supporting the activity of the combination of CDK4/6 inhibitors and endocrine therapy (ET), we hypothesize that palbociclib in combination with ET may be effective as adjuvant therapy in patients with HR+/HER2-negative resected ILRR of BC. Trial design: POLAR is a phase III open-label, multicenter, randomized trial of adjuvant palbociclib in combination with standard ET versus standard ET alone for women and men with histologically confirmed HR+/HER2-negative resected ILRR of BC. Protocol treatment consists of palbociclib (125 mg/d orally for 21 days, followed by 7 days rest) for 3 years plus standard ET for at least 3 years (Arm A) or standard ET for at least 3 years (Arm B). Patients must be enrolled within 6 months of complete gross excision of the ILRR. Patients may have started standard ET prior to entry. Randomization (1:1) is stratified according to (1) gender and menopausal status; (2) planned ET (oral aromatase inhibitor or tamoxifen vs. fulvestrant). The primary endpoint, invasive disease-free survival (iDFS), will be compared between treatment groups using a stratified log-rank test. The sample size provides 80% power to detect a 50% reduction in hazard (HR=0.50) for palbociclib plus ET versus ET-alone, using a log-rank test with two-sided α=0.05 test with 66 iDFS events. The 3-year iDFS is assumed to be 76% on the basis of patients in the CALOR trial who had ER+ ILRRs. Accrual: The trial will recruit 400 patients from approximately 50 Centers in Austria, France, Hungary, Italy, Spain and Switzerland. The first patient was randomized in August 2019. Accrual as of mid-June 2020 was 25 patients. The POLAR trial (IBCSG 59-19 / BIG 18-02) is sponsored and coordinated by IBCSG with financial support from Pfizer. The trial is conducted under the BIG umbrella in collaboration with ABCSG, GEICAM, SOLTI, SAKK and Unicancer. NCT03820830 Citation Format: Elisabetta Munzone, Stefan Aebi, Noelia Martínez Jañez, Uwe Güth, Meritxell Bellet, Barbara Pistilli, Marija Balic, Heidi Roschitzki-Voser, Meredith M Regan. Phase III open-label, multicenter, randomized trial of adjuvant palbociclib in combination with endocrine therapy versus endocrine therapy alone for patients with hormone receptor-positive / HER2-negative resected isolated locoregional recurrence of breast cancer - The POLAR Trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-26-02.