Real-world data in Japan: 1L/2L palbociclib-ET effective in HR-positive/HER2-negative advanced breast cancer

Palbociclib combined with endocrine therapy (ET) is effective in hormone receptor (HR)–positive, HER2-negative advanced breast cancer (ABC) in both first-line (1L) and second-line (2L) settings in the real world, a multicentre observational study in Japan has shown.

The investigators analyzed medical records from 677 ABC patients who initiated palbociclib plus ET as either 1L (n=420; median age, 60 years; female, 99.3 percent; postmenopausal, 71.5 percent) or 2L treatment (n=257; median age, 60 years; female, 99.6 percent; postmenopausal, 68.0 percent) across 20 centres between December 2017 and December 2020. Among patients treated in the 1L setting, after end of adjuvant therapy, 46.0 percent had treatment-free interval (TFI) <12 months, and 20.5 percent had TFI ≥12 months. The remaining 26.0 percent had de novo metastasis or did not receive adjuvant therapy after surgery. [Breast Cancer 2024;doi:10.1007/s12282-024-01575-5]

At treatment initiation, the standard dose of palbociclib (125 mg/day) was administered to 90.5 percent of patients in the 1L setting and 87.2 percent of patients in the 2L setting. Dose reduction was subsequently required in 73.6 percent and 69.3 percent of patients, respectively, with approximately 26 percent receiving 100 mg/day and 40–44 percent receiving 75 mg/day. ET predominantly included fulvestrant (56.4–76.7 percent) and letrozole (16.3–37.9 percent). Median follow-up from palbociclib initiation was 36.3 months.

Median real-world progression-free survival (rwPFS) was 24.5 months and 14.5 months in the 1L and 2L settings, respectively. In the 1L setting, median rwPFS was 33.6 months in patients with de novo metastatic disease or no adjuvant therapy, 14.5 months in those with TFI <12 months, and 27.3 months in those with TFI ≥12 months.

Median overall survival (OS) was not reached in the 1L setting and 46.7 months in the 2L setting, with corresponding 36-month OS rates of 74.4 percent and 60.2 percent. Notably, in the 1L setting, median OS was not reached in patients with de novo metastasis or no adjuvant therapy and those with TFI ≥12 months, and was 50.1 months in those with TFI <12 months. The 36-month OS rates were 80.2 percent, 82.0 percent, and 66.0 percent, respectively.

“Our results demonstrated clinical benefits of palbociclib combined with ET for HR-positive, HER2-negative ABC patients in the 1L and 2L settings, which were comparable to [findings from] phase III PALOMA trials,” the researchers highlighted. [Breast Cancer 2024;doi:10.1007/s12282-024-01575-5; Breast Cancer Res Treat 2019;174:719-729; J Clin Oncol 2024;42:994-1000; Eur J Cancer 2018;104:21-31; Clin Cancer Res 2022;28:3433-3442]

In the study, palbociclib discontinuation rates were 70.0 percent and 81.3 percent in the 1L and 2L settings, respectively, primarily due to disease progression (68.0 percent and 77.5 percent) and adverse events (AEs; 22.4 percent and 18.2 percent). The higher incidence of AEs leading to treatment discontinuation in the study vs phase III trials (PALOMA-2, 7.4–15.6 percent; PALOMA-3, 0.0–2.6 percent) may be attributed to suboptimal AE management during early stages after palbociclib’s launch in Japan and sequential abemaciclib use without proper palbociclib dose reduction or interruption. [Breast Cancer 2024;doi:10.1007/s12282-024-01575-5; N Engl J Med 2016;375:1925-1936; Int J Clin Oncol 2019;24:274-287; N Engl J Med 2015;373:209-219; Int J Clin Oncol 2019;24:262-273]

“Further research is needed to explore the temporal trend in [palbociclib] discontinuation rate and the pattern of palbociclib treatment in patients who received abemaciclib as subsequent therapy,” the researchers noted. [Breast Cancer 2024;doi:10.1007/s12282-024-01575-5]