Nationwide real-world practice pattern and clinical data of palbociclib in HR (+), HER2 (-) metastatic breast cancer patients in Korea (KCSG BR21-15)

Abstract

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have remarkably improved the survival outcome in hormone-receptor-positive (HR+)/human epidermal growth factor-2-negative (HER2-) metastatic breast cancer (mBC). Although PALOMA-2 has met its primary outcome, overall survival (OS) was relatively shorter compared to ribociclib and abemaciclib. In Korea, use of palbociclib + aromatase inhibitor (AI) + gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women is limited, and bilateral salpingo-oophorectomy (BSO) is necessary before treatment. We analyzed the real-world clinical outcome and patient characteristics of letrozole + palbociclib in Korea.

Methods: Between August 2016 and December 2022, 1017 HR+/HER2-postmenopausal women treated with first-line letrozole + palbociclib were enrolled. Primary endpoints were real-world progression-free survival (rwPFS) in total population and survival differences according to menopausal status (natural or induced menopause via BSO).

Results: Patients' median age was 56 (range 27-92) years. Median rwPFS, real-world OS (rwOS) were 28.0 months (95 % confidence interval [CI] 25.5-32.1) and 61.8 months (95 % CI 57.7-70.5), with a median follow-up of 45.1 (IQR, 31.0-56.6) months. BSO group demonstrated similar median rwPFS compared to natural menopause group. Adjuvant tamoxifen ± GnRHa was most frequently prescribed (73.3 %). Primary endocrine resistant mBC patients showed inferior median rwPFS compared to secondary resistant mBC (14.6 vs. 27.1 months, p = 0.0063). Overall response rate was 47.5 %, with a disease control rate of 89.6 %.

Conclusion: This is the largest country-based real-world study on palbociclib + letrozole in Asia. Palbociclib demonstrated median rwOS over 60 months, comparable to other pivotal trials.

Keywords: Asia; Hormone receptor–positive breast cancer; Korea; Palbociclib; Real-world data.

Fig. 1

Survival Outcomes. (A) Median PFS in total patient population. (B) Median PFS according to method of menopause. (C) Median OS of total patient population. (D) Median OS according to method of menopause.

Fig. 2

Survival outcomes according to endocrine resistance and TFI in recurrent patient population. (A) Median PFS according to primary or secondary endocrine resistance. (B) Median OS according to endocrine resistance. (C) Median PFS according to TFI <12 months or ≥ 12 months. (D) Median OS according to TFI.

Fig. 3

Survival outcomes according to tamoxifen resistance and TFI in recurrent patient population who received adjuvant tamoxifen. (A) Median PFS according to primary or secondary tamoxifen resistance. (B) Median OS according to tamoxifen resistance. (C) Median PFS according to TFI < 12 months or ≥ 12 months. (D) Median OS according to TFI.

Supplementary Fig. 1

Consort diagram.

Supplementary Fig. 2

Survival outcomes according to luminal subtype or recurrence status. (A) Median PFS according to luminal A or B-like subtype. (B) Median PFS according to De novo or recurrent breast cancer status. (C) Median OS according to luminal subtype. (D) Median OS according to recurrent status.

Supplementary Fig. 3

Forest plot in total patient population. (A) Subgroup analysis of PFS. (B) Subgroup analysis of OS.

Supplementary Fig. 4

(A) Median PFS2 among patients who received second-line treatment after progression of letrozole + palbociclib. (B) Median PFS2 according to second-line cytotoxic chemotherapy or endocrine treatment.