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.


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).


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.


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.


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.


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.


This trial is registered at NCT03423199 and UMIN000030816. For more information, email [email protected]

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.