Abstract P4-01-26: Real-world treatment duration of subsequent therapy after palbociclib (PAL) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) in Japan
Authors: Sawaki Masataka , Muramatsu Yasuaki , Togo Kanae , Iwata Hiroji 
Published: March 2023

Abstract
Background: PAL is a first-in-class cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) for the treatment of HR+/HER2− ABC. Two CDK4/6is are currently available in Japan; PAL and abemaciclib (ABE). CDK4/6i+endocrine therapy (ET) has shown significant clinical benefits compared to ET alone in clinical trials. CDK4/6i combination therapy is strongly recommended as a first-line (1L) treatment in global and Japanese treatment guidelines. However, no optimal subsequent treatment has been established after discontinuing treatment with CDK4/6i+ET. Substantial data are required to determine whether the available treatment options remain effective after CDK4/6i treatment. Here, we report the treatment pattern of subsequent therapy after PAL in a real-world setting in Japan to provide insights into the optimal subsequent therapy.
Methods: This retrospective, observational study utilized a nationwide hospital-based medical claims database managed by Medical Data Vision (MDV). The MDV database, one of the largest medical databases in Japan, covers 26% of acute-care hospitals across Japan, including 226 cancer therapeutic facilities. We evaluated the data of patients who received PAL from September 2017 to June 2021 and subsequently received therapy. Any treatment for ABC initiated within 30 days was considered part of one regimen. The median time-to-treatment failure (TTF) of subsequent therapy was estimated using the Kaplan–Meier method.
Results: From the database, we identified 1,170 patients with HR+/HER2− ABC who received PAL, among which 398 (34%) received combination therapy as 1L treatment. The median age at PAL initiation was 64 years (range 53–72), and 13.0% of the patients were pre-/peri-menopausal. Among the 398 patients, 224 (56.3%) received therapy after PAL+ET. Endocrine-based therapy was commonly used as the first subsequent therapy (n=136; 60.7%), including CDK4/6i+ET (n=70; 31.2%), ET alone (n=39; 17.4%), and everolimus+ET (n=27; 12.1%). Among the 81 (36.2%) patients who received chemotherapy as the first subsequent therapy, 27 (12.1%) received bevacizumab+chemotherapy. The median TTF (95% confidence interval [CI]) of the first subsequent therapy was 7.5 months (6.5–8.4), and that of each subsequent regimen is listed in Table 1. The median TTF (95% CI) for patients received CDK4/6i+ET as first subsequent therapy after PAL+ET was the longest among the regimens, 10.9 months (6.5–15.6). Among the 70 patients, 36 changed only CDK4/6i type, 17 changed only ET type, and 12 changed both CDK4/6i and ET types. The median TTF (95% CI) was 20.1 months (6.5– not reached [NR]), 8.7 months (2.9–11.2), and 7.7 months (2.6–NR), respectively. No obvious trend was observed between the TTF of PAL+ET as a 1L treatment and the TTF of subsequent ABE after the PAL+ET treatment.
Conclusion: More than half the patients received endocrine-based therapy after PAL+ET as a 1L treatment, and the observed treatment duration was comparable to the results of clinical trials reported to date, even after PAL treatment. ET+targeted therapy and chemotherapy represent acceptable treatment options after PAL+ET. One-third of patients received CDK4/6i+ET after PAL+ET in Japanese clinical practice; however, further investigation is warranted to confirm that this treatment strategy is effective.
Table 1. Median TTF of each subsequent therapy after PAL+ET
Citation Format: Masataka Sawaki, Yasuaki Muramatsu, Kanae Togo, Hiroji Iwata. Real-world treatment duration of subsequent therapy after palbociclib (PAL) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) in Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-26.