Endocrine therapy-based strategies with different endocrine sensitivity statuses for hormone receptor positive/HER2 negative metastatic breast cancer: A network meta-analysis.

person Jiani Wang National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China info_outline Jiani Wang, Yiqun Han, Jiayu Wang, Binghe Xu

Authors person Jiani Wang National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China info_outline Jiani Wang, Yiqun Han, Jiayu Wang, Binghe Xu Organizations National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Abstract Disclosures Research Funding No funding received None Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Since the absence of direct head-to-head comparisons for all regimens, decision-making guidelines are urgently needed for different endocrine sensitivity statuses. This study is to evaluate the efficacy of ET-based regimens in patients with HR+/HER2- MBC and to assess the heterogeneity among different compounds with a particular focus on their ability to improve survival outcomes. Methods: This network meta-analysis of phase II/III randomized controlled trials (RCTs) with at least one ET in HR+/HER2- MBC were enrolled. Based on the endocrine responses, participants were stratified into endocrine therapy sensitivity (ETS) and endocrine therapy resistance (ETR) groups. Primary endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed by bayesian algorithms and primarily measured as surface under the cumulative ranking curve (SUCRA). Results: A total of 42 trials (22917 patients) were included. Regarding PFS, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) +fulvestrant 500mg (F500) was recommended for the ETS group (SUCRA = 76.92%), while chemotherapy was considered as the most effective option for the ETR group (SUCRA = 73.47%). For visceral metastases, CDK4/6i +aromatase inhibitors (AIs) could provide the extreme efficacy for the ETS group (SUCRA = 63.27%) while the CDK4/6i +F500 (SUCRA = 76.17%) as the prior regimen for the ETR group. For bone-only disease, CDK4/6i+F500 was preferred for both the ETS (SUCRA = 67.04%) and the ETR (SUCRA = 70.24%) group. Concerning OS, CDK4/6i+tamoxifen was estimated as the first-rank regimen for the ETS subgroup (SUCRA = 67.04%) and chemotherapy for the ETR subgroup (SUCRA = 60.02%). Regarding resistance category, abemaciclib +F500 was likely the best option with PFS, for both primary (SUCRA = 69.19%) and secondary ETR (SUCRA = 69.09%) settings, as well as primary ETR associated with OS improvement (SUCRA = 67.67%). Pictilisib +F500 could be the optimal treatment with OS for secondary ETR (SUCRA = 60.50%)group. Conclusions: The results showed that CDK4/6i + F500 was probably the most promising option in ETS, visceral ETR and bone-only disease settings in terms of PFS. OS subgroup analysis showed that different endocrine sensitivity statuses required various optimal treatment strategies.