폐경 후 한국인 여성에서 호르몬 수용체 양성, HER2 음성 전이성 유방암에 대한 1차 내분비 요법으로 palbociclib 과 letrozole 병합 치료의 효과 및 안정성에 대한 후향적 분석

Abstract

Background: Palbociclib selectively inhibits cyclin-dependent kinase 4/6 to regulate cell cycle. Based on the results of the PALOMA-2 study which showed palbociclib plus letrozole combination therapy was effective for postmenopausal women with hormone receptor (HR)-positive and HER2-negative advanced breast cancer (ABC), palbociclib was approved in Korea in June 2017. We report the real-world outcomes of palbociclib plus letrozole combination therapy for Korean patients. Material and Methods: This study is a retrospective cohort study of patients treated with palbociclib plus letrozole for postmenopausal women with HR-positve, HER2-negative ABC at the Asan Medical Center, Seoul, Korea between June 2017 and August 2019. Primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety. Results: A total of 204 patients (pts) were enrolled with median age of 53 years (range, 29-82), 135 (66.2%) with visceral metastases and 80 (39.2%) received bilateral salpingo-oophorectomy (BSO) . Median follow-up period was 19.2 months (mo) (range, 1.4 to 39.8). The median PFS was 26.0 mo (95% confidence interval [CI], 19.9 to 26.1) and the median OS was not reached. The median PFS of pts who underwent BSO was 26.0 mo (95% CI, 19.9 to 26.0) and was not reached in those with natural menopause. ORR was 38.2% (95% CI, 31.5 to 45.2), and CBR was 81.9% (95% CI, 75.8 to 86.8). The most common adverse events of any grade were neutropenia (95.0%), followed by anemia (51.4%), thrombocytopenia (33.3%), stomatitis (22.5%), fatigue (18.1%). The most frequently reported grade ≥3 adverse events were neutropenia (83.3%, 170/204), but febrile neutropenia occurred only in 4 (2.0%) pts. Dose reduction of palbociclib was required in 164 (80.4%) pts due to neutropenia and was stopped in 2 pts due to grade 4 neutropenia and thrombocytopenia. Conclusions: Palbociclib plus letrozole in Korean pts with HR-positive, HER2-negative ABC demonstrated comparable efficacy to pivotal phase 3 trial. Although dose reductions of palbociclib due to hematologic toxicities were required more frequently in this population, dose adjustments seemed not affect the treatment outcome.