Abstract PO1-06-03: Efficacy of First-line Treatments for Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer: A Systematic Literature Review and Network Meta-analysis Feasibility Assessment
Authors: Sharma Priyanka , Dang Chau , Drudge Christopher , Debnath Amrita , Rai Manvir , Gauthier Eric , Broughton Edward 
Published: May 2024

Abstract
Background:
A comprehensive summary of clinical evidence for first-line (1L) treatments for hormone receptor-positive, human epidermal growth factor receptor 2-positive (HR+/HER2+) advanced or metastatic breast cancer (mBC) is needed to understand which treatments have been evaluated and the outcomes associated with different treatments. Understanding the available clinical evidence for HR+/HER2+ mBC 1L treatments can also inform the feasibility of network meta-analyses (NMAs) to estimate relative treatment effects where head-to-head trials are not available. The objective was to prepare a systematic summary of clinical trials of 1L treatments for HR+/HER2+ mBC and assess the feasibility of NMAs for key efficacy outcomes.
Methods:
A systematic literature review (SLR) was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials evaluating 1L treatments for adults with HR+/HER2+ mBC published between January 2000 and January 2023 were identified via predefined searches of databases (Embase, MEDLINE, Cochrane Library), relevant congress proceedings, and ClinicalTrials.gov (updating a previous SLR covering January 2000 to December 2020). Study design characteristics, patient characteristics, and efficacy outcomes were extracted from identified trials. An NMA feasibility assessment that considered network connectivity and cross-study heterogeneity was conducted for four efficacy outcomes of interest: progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR).
Results:
After screening, 37 records reporting on 23 unique studies (11 randomized controlled trials [RCTs] and 12 single-arm trials; 35 study arms in total) were selected. Included trials were mostly phase II or phase III multi-country studies that evaluated a HR+ or HER2+ population, with outcomes being reported for the subgroup of patients with the HR+/HER2+ subtype. Treatments evaluated included one or two anti-HER2 therapies (AHTs) + endocrine therapy (ET) (5/35 study arms), AHTs + chemotherapy (CT) (20/35), AHTs + ET + CT (2/35), AHTs alone (5/35), and ET alone (3/35). For HR+/HER2+ patients, PFS and OS were reported by 17/23 and 10/23 studies, respectively. Reported median PFS and OS ranged from 2.4-23.7 months and 23.9-66.7 months, respectively. Among the 11 included RCTs, hazard ratios and/or Kaplan-Meier curves, which were considered a requirement for NMAs for time to event outcomes, were reported for PFS and OS by 9 and 6 studies, respectively. Among these studies, reported median PFS and OS ranged from 2.4-19.2 months and 23.9-57.9 months, respectively. For HR+/HER2+ patients, ORR and CBR were reported by 13/23 and 6/23 studies, respectively. Assuming all CTs could be considered equivalent treatments and all ETs could be considered equivalent treatments, NMAs involving networks of 9, 6, 6, and 3 treatments were feasible for PFS, OS, ORR, and CBR, respectively. Some patient characteristics including time since mBC diagnosis and proportion with bone metastases were not reported consistently across trials. However, included studies were broadly comparable based on study design characteristics, outcome definitions and other reported patient characteristics such as age and Eastern Cooperative Oncology Group performance status.
Conclusion:
Clinical trials in 1L HR+/HER2+ mBC have evaluated various combinations of AHTs, CTs, and ETs, with most study arms being AHTs + CT. Although efficacy outcomes of interest were not consistently reported across trials, NMAs were found to be feasible for PFS, OS, ORR, and CBR based on available data.
Citation Format: Priyanka Sharma, Chau Dang, Christopher Drudge, Amrita Debnath, Manvir Rai, Eric Gauthier, Edward Broughton. Efficacy of First-line Treatments for Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer: A Systematic Literature Review and Network Meta-analysis Feasibility Assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-03.