Abstract OT2-02-06: Palbociclib in combination with trastuzumab and endocrine therapy (ET) versus treatment of physician's choice (TPC) in metastatic HER2-positive and hormone receptor-positive (HER2+/HR+) breast cancer with PAM50 luminal intrinsic subtype (SOLTI-1303 PATRICIA II): A multi-center, randomized, open-label, phase II trial

Background: Efficacy Interim results from PATRICIA phase II trial in HER2+/HR+ advanced breast cancer (BC) showed that PAM50 luminal disease was associated with larger and clinically meaningful progression-free survival (PFS) following palbociclib, trastuzumab and endocrine therapy compared to PAM50 non-luminal disease (Ciruelos E. et al, SABCS 2018). Based on these preliminary results, PATRICIA II was designed to select patients based on PAM50 and to include a randomization to a control arm. Trial Design: PATRICIA II is a randomized open-label, adaptive design, phase II study. Eligible patients must have centrally confirmed HR+/HER2+ and PAM50 Luminal A or B intrinsic subtype tumors and have received at least 1 (and no more than 4) prior lines of anti-HER2 regimens for locally advanced or metastatic BC, including a taxane and trastuzumab. Patients are randomized 1:1 to receive trastuzumab in combination with palbociclib at a standard dose of 125 mg/day orally 3 weeks on/1 week off and endocrine therapy (cohort C1) or treatment of physician’s choice (TPC): TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin, paclitaxel or docetaxel) in combination with trastuzumab (cohort C2). ET options are either an aromatase inhibitor, fulvestrant or tamoxifen. Premenopausal patients (pts) must receive ovarian suppression. Stratification factors include number of previous regimens for advanced BC (1-2 vs 3-4) and the presence of visceral disease (yes vs no). The primary objective is to assess whether the combination of palbociclib, trastuzumab and endocrine therapy is superior to TPC in terms of progression-free survival (PFS) in HER2+, PAM50 Luminal patients. The study has an 80% power with two-sided alpha=0.05 to detect a hazard ratio of 0.62 in favor of the palbociclib arm. An adaptive design will be used to compare both treatment arms. An interim analysis (IA) adjusted for multiplicity from O’Brien-Fleming method and an estimation of the conditional power (CP) will be performed at 70% of the events by an Independent Data Monitoring Committee (IDMC). Key secondary objectives are response rate, overall survival, safety, and Quality of Life. Tumor tissue and blood samples will be collected for biomarker analyses. A total of 516 patients will be screened and 232 patients will be recruited. The trial was activated in June 2019 and the recruitment is ongoing in 20 sites in Spain. The study is sponsored by SOLTI and financially supported by Pfizer. Citation Format: Eva Ciruelos, Patricia Villagrasa, Mafalda Oliveira, Sonia Pernas, Javier Cortes, Silvia Vazquez, Noelia Martinez, Antonia Perello, Begona Bermejo, Eduardo Martinez, Isabel Garau, Mireia Mele, Alvaro Montano, Estela Vega, Blanca Cantos, Maria Jose Echarri, Tomas Pascual, Jordi Canes, Pamela Celiz, Xavier Gonzalez, Aleix Prat. Palbociclib in combination with trastuzumab and endocrine therapy (ET) versus treatment of physician9s choice (TPC) in metastatic HER2-positive and hormone receptor-positive (HER2+/HR+) breast cancer with PAM50 luminal intrinsic subtype (SOLTI-1303 PATRICIA II): A multi-center, randomized, open-label, phase II 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 OT2-02-06.