Abstract OT2-02-07: Fulvestrant with additional palbociclib in advanced or metastatic hormone receptor-positive HER2-negative breast cancer after progression to fulvestrant monotherapy: JBCRG- M07 (FUTURE trial)

Background: Fulvestrant is one of the standard treatments for first- and second-line endocrine therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC). Palbociclib inhibits cyclin dependent kinase (CDK) 4 and CDK6 in vitro, resulting in loss of RB1 phosphorylation. Palbociclib has high activity in HR-positive breast cancer cell lines and is synergistic in combination with endocrine therapies. The PALOMA-3 trial enrolled patients with metastatic estrogen receptor (ER)-positive breast cancer with resistance to aromatase inhibitor. The results demonstrated that palbociclib combined with fulvestrant was associated with significantly longer progression-free survival (PFS) than fulvestrant alone. However, patients in the trial reported higher rates of adverse events, such as neutropenia and alopecia, compared with fulvestrant monotherapy. We investigate in this prospective cohort study that the addition of palbociclib to fulvestrant is effective and safe in HR-positive and HER2-negative advanced breast cancers that progressed during fulvestrant monotherapy. Specific Aims: Primary objective: To observe the PFS in patients with resistance to fulvestrant monotherapy who were treated with fulvestrant plus palbociclib. Secondary Objective: To observe the PFS in patients treated with fulvestrant as the first and second line therapy. We also aim to observe overall survival and safety. A prospective translational research is also planned to assess the correlations between biomarkers and response. Trial Design: Single arm exploratory trial Eligibility Criteria: Eligible patients must have historically confirmed ER-positive and HER2-negative MBC who received fulvestrant as first or second line therapy. Prior chemotherapy in the neoadjuvant and adjuvant settings and up to one line of chemotherapy in MBC is permissible. Patients who received CDK4/6 inhibitor as metastatic therapy are excluded. Statistical Design: We aim to set the lowest limit of the therapeutic effect at a median PFS of 5 months, which is the value reported in the PALOMA-3 study. If we assume that the expected median PFS is 8 months, at least 63 patients are required to reject the null hypothesis (5 months) with a power of 80% under a one-sided alpha at 0.05. The length of the accrual period and follow-up period are set at 12 and 18 months, respectively. Target Accrual: First registration: 200 patients with fulvestrant monotherapy as the first and second line setting. Second registration: 70 patients with combined palbociclib and fulvestrant. (UMIN 000029294) Citation Format: Kokoro Kobayashi, Naoki Niikura, Shigehira Saji, Takayuki Iwamoto, Nobutaka Iwakuma, Yuichiro Kikawa, Norikazu Masuda, Kenichi Watanabe, Takashi Takeshita, Mari Oba, Shinji Ohno. Fulvestrant with additional palbociclib in advanced or metastatic hormone receptor-positive HER2-negative breast cancer after progression to fulvestrant monotherapy: JBCRG- M07 (FUTURE trial) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-07.