Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL)
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.
Abstract
Purpose YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.
참고문헌 (23)
- Preusser M, "CDK4", 6 inhibitors in the treatment of patients with breast cancer : summary of a multidisciplinary round-table discussion, 2018, pp.3, e000368~
- Marra A, "Are all cyclin-dependent kinases 4", 6 inhibitors created equal?, 2019, pp.5, 27~
- Shah AN, "Hormone receptor-positive", human epidermal growth receptor 2-negative metastatic breast cancer in young women : emerging data in the era of molecularly targeted agents, 2020, pp.25, e900~8
- Finn RS, "Palbociclib and letrozole in advanced breast cancer", N Engl J Med, 375, pp.1925~1936 (2016)
- Cristofanilli M, "Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy(PALOMA-3) : final analysis of the multicentre, double-blind, phase 3 randomised controlled trial", Lancet Oncol, 17, pp.425~439 (2016)
- Park YH, "Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer(KCSG-BR15-10) : a multicentre, openlabel, randomised, phase 2 trial", Lancet Oncol, 20, pp.1750~1759 (2019)
- Kim JY, "Clinical features and outcomes of invasive breast cancer : age-specific analysis of a modern hospital-based registry", J Glob Oncol, 5, pp.1~9 (2019)
- Yeo W, "Treating HR+", HER2-breast cancer in premenopausal Asian women : Asian Breast Cancer Cooperative Group 2019 Consensus and position on ovarian suppression, 2019, pp.177, 549~559
- Finn RS, "Impact of prior treatment on palbociclib plus letrozole (P+L) efficacy and safety in patients (pts) with estrogen receptor-positive", human epidermal growth factor receptor 2-negative (ER+, Ann Oncol, pp.2017, 28(Suppl 5)[DOI]
- Cardoso F, "4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer(ABC 4)", Ann Oncol, 29, pp.1634~1657 (2018)
- Taylor CW, "Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer : an intergroup study", J Clin Oncol, 16, pp.994~999 (1998)
- Anders CK, "Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression", J Clin Oncol, 26, pp.3324~3330 (2008)
- Liao S, "The molecular landscape of premenopausal breast cancer", Breast Cancer Res, 17, pp.104~ (2015)
- Kan Z, "Multiomics profiling of younger Asian breast cancers reveals distinctive molecular signatures", Nat Commun, 9, pp.1725~ (2018)
- Yap YS, "Insights into breast cancer in the East vs the West : a review", JAMA Oncol, 5, pp.1489~1496 (2019)
- Lin CH, "Contrasting epidemiology and clinicopathology of female breast cancer in Asians vs the US population", J Natl Cancer Inst, 111, pp.1298~1306 (2019)
- Anders CK, "Breast cancer before age 40 years", Semin Oncol, 36, pp.237~249 (2009)
- Park YH, "Prevalence and clinical outcomes of young breast cancer(YBC)patients according to intrinsic breast cancer subtypes : Single institutional experience in Korea", Breast, 24, pp.213~217 (2015)
- Ahn SH, "Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance : nationwide survival data in Korea : a report from the Korean Breast Cancer Society", J Clin Oncol, 25, pp.2360~2368 (2007)
- Kim TY, "Abstract P1-09-09: role of endocrine therapy in premenopausal patients with hormone receptor-positive metastatic breast cancer, compared with postmenopausal patients: diachronic analyses from nationwide cohort in Korea (KCSG BR 14-07)", Cancer Res, 76(4 Suppl), pp.P1-09-09~ (2016)
- Tripathy D, "Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer(MONALEESA-7) : a randomised phase 3 trial", Lancet Oncol, 19, pp.904~915 (2018)
- Im SA, "Overall survival with ribociclib plus endocrine therapy in breast cancer", N Engl J Med, 381, pp.307~316 (2019)
- Turner NC, "Overall survival with palbociclib and fulvestrant in advanced breast cancer", N Engl J Med, 379, pp.1926~1936 (2018)