Palbociclib plus tamoxifen ± goserelin in women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer (BC): PATHWAY, an Asian international double-blind randomized phase 3 trial—Final overall survival (OS) analysis.

Abstract

LBA1018 Background: In Asia, BC incidence is increasing and peaks before menopause; tamoxifen is commonly used for pre/perimenopausal BC. However, tamoxifen was not approved for use in combination with CDK4/6 inhibitors in many countries. PATHWAY previously showed significantly improved progression-free survival (PFS) for palbociclib plus tamoxifen (± goserelin) at the primary analysis (data cut-off 15 Sep 2022) with immature OS. Here, we report updated PFS and final OS. Methods: This phase 3 trial was conducted in Japan, Korea, Taiwan, and Singapore (NCT03423199). Eligible patients were women with locally advanced or metastatic HR-positive, HER2-negative BC who were candidates for 1st- or 2nd-line tamoxifen-based endocrine therapy and had not received a prior CDK4/6 inhibitor. Patients were randomized 1:1 to receive palbociclib (125 mg daily, days 1–21 of a 28-day cycle) or placebo, each with tamoxifen 20 mg daily. Pre/perimenopausal patients also received goserelin. Randomization was stratified by line of therapy and menopausal status. Investigator-assessed PFS (primary endpoint) and OS were analyzed using Kaplan–Meier methods and compared using a stratified log-rank test with 1-sided p values; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a stratified Cox proportional hazards model. Results: 184 patients were randomized (Feb 2018–Jul 2019) at 22 sites. Overall, 28.3% were pre/perimenopausal and 71.7% postmenopausal; 60.9% received study treatment as 1st-line and 39.1% as 2nd-line endocrine therapy. At the end of study in October 2025, 154 PFS events and 105 deaths occurred. Updated PFS remained significantly improved with palbociclib plus tamoxifen vs placebo plus tamoxifen (HR 0.594; 95% CI, 0.427–0.825; P < 0.001), with median PFS 24.4 months (95% CI, 13.1–32.4) vs 11.1 months (95% CI, 7.4–14.6), respectively. PFS benefit was observed regardless of menopausal status (pre/perimenopausal: HR 0.343; 95% CI, 0.175–0.675; postmenopausal: HR 0.697; 95% CI, 0.479–1.012). Final OS also favored palbociclib plus tamoxifen (HR 0.772; 95% CI, 0.525–1.134; P = 0.093), with median OS 71.7 months (95% CI, 57.1–not estimable) vs 62.0 months (95% CI, 49.9–73.1); OS results were consistent across menopausal subgroups (pre/perimenopausal: HR 0.747; 95% CI, 0.339–1.647; postmenopausal: HR 0.772; 95% CI, 0.497–1.198). Palbociclib plus tamoxifen was generally well tolerated; adverse events were manageable with dosing interruptions/dose reductions, and no new safety findings. Conclusions: With longer follow-up, palbociclib plus tamoxifen (± goserelin) provided durable PFS benefit and a favorable OS trend with manageable safety, supporting this regimen as an effective option regardless of menopausal status. Clinical trial information: NCT03423199 .