Abstract OT3-02-02: PATHWAY: Asian, multicenter, phase 3 trial of tamoxifen with or without palbociclib ± goserelin in women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer
Authors: Noguchi E , Hata T , Nakamura K , Kuchiba A , Hayashi M , Hamada A , Yonemori K , Sohn J , Lu Y-S , Yap Y-S , Fujiwara Y , Tamura K 
Published: May 2019

Abstract
BACKGROUND:
The incidence rates of breast cancer (BC) in Asian counties have been rising rapidly. The age-specific female BC incidence rates peak before menopause (around 40-50 years of age) in Asia, however treatment options for pre/perimenopausal patients are limited. Palbociclib (P) is an oral novel cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The addition of P to endocrine therapy (ET) such as aromatase inhibitor or fulvestrant has been demonstrated improved progression-free survival (PFS) in phase 3 studies PALOMA-2 and PALOMA-3. This study is designed to evaluate efficacy and safety of P plus tamoxifen (TAM) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic BC regardless of menopausal status. This study is conducted as a Clinical Research Collaboration by National Cancer Center Hospital with research funding from Pfizer.
TRIAL DESIGN:
PATHWAY/NCCH1607 is a double-blind, placebo-controlled, randomized, phase 3 study. Patients will be randomized 1:1 to receive either P (125 mg once daily, days1-21 of a 28-day cycle) or placebo in combination with TAM (20 mg once daily, continuously). Pre/perimenopausal women should receive concurrent ovarian function suppression with goserelin. Randomization will be stratified by prior ET for advanced/metastatic BC (1st line ET vs. 2nd line ET) and menopausal status (pre/perimenopausal vs. postmenopausal).
KEY ELIGIBILITY CRITERIA:
Eligible patients include women of any menopausal status with HR-positive, HER2-negative advanced or metastatic BC; candidates to receive TAM as 1st line or 2nd line ET for advanced/metastatic disease; ≥18 years of age; measurable or non-measurable disease (RECIST v.1.1); ECOG performance status 0-1; adequate organ function; have not received treatment with TAM (except for patients who have had more than 12 months from completion of adjuvant therapy with TAM); and have not received any CDK4/6 or phosphoinositide 3-kinase (PI3K) - mammalian target of rapamycin (mTOR) inhibitors.
SPECIFIC AIMS:
The primary endpoint is PFS as assessed by the investigator. Secondary endpoints include overall survival (OS), 1, 2, and 3-year survival probabilities, objective response (OR), duration of response, clinical benefit rate (CBR), pharmacokinetics, safety, and patient-reported outcomes.
STATISTICAL METHODS:
The sample size was determined to detect a 38% reduction in the hazard of disease progression or death in P plus TAM arm with a 1-sided significance level of 2.5% and power of 80%. A stratified log rank test will be used to compare PFS between the 2 treatment arms.
PRESENT ACCRUAL AND TARGET ACCRUAL:
Target accrual of 180 patients will be enrolled within 23 sites among Japan, Korea, Taiwan, and Singapore. As of June 2018, 46 patients have been enrolled.
CONTACT INFORMATION:
This trial is registered at ClinicalTrials.gov NCT03423199 and UMIN000030816. For more information, email NCCH1607_office@ml.res.ncc.go.jp
Citation Format: Noguchi E, Hata T, Nakamura K, Kuchiba A, Hayashi M, Hamada A, Yonemori K, Sohn J, Lu Y-S, Yap Y-S, Fujiwara Y, Tamura K. PATHWAY: Asian, multicenter, phase 3 trial of tamoxifen with or without palbociclib ± goserelin in women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-02.