Abstract PO3-04-10: Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy in Japanese patients with HR+/HER2- ABC in the first- or second-line setting: A multicenter observational study
Authors: Masuda Norikazu , Hattori Masaya , Yoshinami Tersuhiro , Okamura Takuho , Watanabe Ken-ichi , Nakayama Takahiro , Masuda Hiroko , Tsuneizumi Michiko , Takabatake Daisuke , Harao Michiko , Yoshino Hiroshi , Mori Natsuko , Yasojima Hiroyuki , Oshiro Chiya , Iwase Madoka , Yamaguchi Miki , Sangai Takafumi , Sasada Shinsuke , Ishida Takanori , Futamura Manabu , Kosaka Nobuyoshi , Shibasaki Yoshiyuki , Nagai Shigenori 
Published: May 2024

Abstract
Introduction
Palbociclib (PAL), a selective, oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), plus (+) endocrine therapy (ET) is standard therapy for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) and was launched in December 2017 in Japan. Efficacy and safety of PAL + ET was shown by randomized clinical studies, PALOMA-2 and PALOMA-3. Further, recent large real-world studies, P-REALITY/P-REALITY X, confirmed effectiveness of PAL+ aromatase inhibitor (AI) for HR+/HER2- ABC in routine United States clinical practice. However, there is limited real-world evidence (RWE) for PAL in Japan. To strengthen the RWE of PAL+ET for HR+/HER2- ABC treatment under different clinical practice and healthcare system, we examine the real-world effectiveness of PAL + ET as 1st line (1L) and 2nd line (2L) treatment for HR+/HER2- ABC in Japan.
Methods
In this multicenter, observational study, patients with HR+/HER2- ABC, who initiated PAL + ET from 15 December 2017 to 31 December 2020 were enrolled. To reduce selection bias, all patients who started PAL during the above period were listed and their eligibility confirmed. Eligible patients had 1) diagnosis of HR+/HER2- ABC; 2) received PAL + ET as 1L or 2L treatment; 3) at least 6 months of follow up from start of PAL or died within that period. The 1L treatment was defined as the first systemic therapy received for ABC regardless of recurrence timing if receiving adjuvant treatment. The subsequent treatment after 1L treatment was defined as a 2L treatment. The primary endpoint was real-world progression-free survival (rwPFS) defined as the time from PAL+ET start to physician-documented disease progression or death due to any cause, whichever occurs first. Secondary endpoints included overall survival (OS), and chemotherapy-free survival (CFS). Results were stratified by treatment line (ie. 1L or 2L). rwPFS, OS, and CFS were analyzed with the Kaplan-Meier method (NCT05399329).
Results
In this study, 677 patients were enrolled. Among them, 419 (62%) patients and 258 (38%) patients received PAL + ET as 1L and 2L, respectively. The median age was 59.0 (range 29-87)　and 470 patients (69.8%) were postmenopausal. 49.0% patients had visceral involvement and 63.8% had a disease-free interval &gt;24 months, defined as date of breast cancer surgery to the diagnosis date of recurrence, and 26.9% had de novo metastatic disease. The starting dose of PAL was 125 mg (89%), 100mg (9%), and 75mg (2%); dose reductions during the treatment period were required for 72% of patients. The most common ET combined with PAL was fulvestrant (FUL; 56.3% in 1L, 76.7% in 2L) followed by letrozole (LET; 37.9% in 1L, 16.3% in 2L). After a median follow-up of 36.2 months, the median rwPFS (95% CI) was 24.5 months (19.9-29.4) for 1L treatment and 14.5 months (10.2-18.3) for 2L treatment. Among the 604 patients initiating at 125 mg/day, the median rwPFS was 25.6 months (21.3-30.4) for 1L treatment and 14.3 months (9.7-18.3) for 2L treatment. Although median OS was not reached (NR) in 1L, median OS of 2L was 44.1 months (39.2 -NR). The 48-months OS rates for 1L and 2L treatment were 62.0% (55.4-67.9) and 48.4 % (40.4-55.9), respectively. The median CFS was 36.7 months (31.8-43.9) for 1L treatment and 23.8 months (20.5-27.3) for 2L treatment.
Conclusions
Our real-world data are consistent with findings form the PALOMA-2 and PALOMA-3 studies and those from RWE in routine United States clinical practice. FUL was the most commonly endocrine partner with PAL regardless of treatment lines. These observations add to the body of evidence supporting PAL effectiveness in clinical practice for Japanese ABC patients.
Citation Format: Norikazu Masuda, Masaya Hattori, Tersuhiro Yoshinami, Takuho Okamura, Ken-ichi Watanabe, Takahiro Nakayama, Hiroko Masuda, Michiko Tsuneizumi, Daisuke Takabatake, Michiko Harao, Hiroshi Yoshino, Natsuko Mori, Hiroyuki Yasojima, Chiya Oshiro, Madoka Iwase, Miki Yamaguchi, Takafumi Sangai, Shinsuke Sasada, Takanori Ishida, Manabu Futamura, Nobuyoshi Kosaka, Yoshiyuki Shibasaki, Shigenori Nagai. Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy in Japanese patients with HR+/HER2- ABC in the first- or second-line setting: A multicenter observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-10.