Abstract P4-13-13: Meta-analyses of visceral versus non-visceral metastases treated by AI & SERD agents as 2nd line endocrine therapy (ET) for HR+ breast cancer (BC)
Authors: Robertson JFR , Di Leo A , Johnston S , Chia S , Bliss J , Bradbury I , Campbell C 
Published: May 2019

Abstract
There is a prevailing belief that ET for HR+ advanced BC is not as effective in patients with visceral metastases (VM) compared to non-visceral metastases (nVM), particularly with later lines of ET. Recently fulvestrant 500mg (Ful 500), has been reported to have greater efficacy in nVM compared to i) VM treated by Ful 500 but also compared to ii) nVM treated by Ful 250 (2nd line) and iii) nVM treated by aromatase inhibitor (AI), anastrozole (1st Line) – implying both site and agent related efficacy. Absence of significant overall survival (OS) difference in PALOMA 3 (2nd line) has increased the debate regarding when to add CDK 4/6is to ET, especially given the OS advantage for Ful 500 monotherapy in the 1st & 2nd line settings.
Patients & Methods: Anonymised, individual patient level data was obtained from randomised controlled trials (RCTs) involving AI & SERD used as mono-theraphy in 2nd or 3rd Line setting in known HR+ BC. All the trials were Phase 3 double-blind, placebo RCTs. All were rigorously assessed for clinical benefit (CB), progression free survival (PFS), duration of CB (DoCB) and OS. Details of the studies, types of ET and patient numbers are shown in the Table.
Results: Outcome data is presented for each study and then summarised under AI, SERD (Ful 250 or 500) and 'all Ets combined'. Odds ratios (Ors) & hazard ratios (HRs) for VM versus nVM by endocrine agents are shown in the Table.
AgentStudyTotal Pats.HR+ Pats.CBRPFSOSDoCBAI(n)(n)OR (95%Cis)HR (95%Cis)HR (95%Cis)HR (95%Cis)Exe00202301831.181.441.271.50Exe00211931681.151.951.832.12AnaEFECT3403360.941.521.201.10AnaSOFEA2492491.291.181.051.41subtotal7636871.11 (0.84-1.48)1.47*** (1.22-1.79)1.21* (1.01-1.45)1.43** (1.10-1.86)SERDFul 25000202191601.791.701.401.23Ful 25000212041771.281.811.322.06Ful 250EFECT3513450.791.401.311.03Ful 250SOFEA2312310.701.171.242.22Ful 250CONFIRM1521521.131.071.510.84Subtotal9268341.05 (0.75-1.45)1.39*** (1.16-1.67)1.34*** (1.14-1.57)1.36 (0.93-1.98)SERDFul 500CONFIRM1441442.24 (1.12-4.48)1.30 (0.90-1.87)1.33 (1.14-1.57)0.97 (0.55-1.66)All ETsTotal183316651.13 (0.92-1.39)1.42*** (1.26-1.59)1.28*** (1.14-1.44)1.35** (1.09-1.66)
[Pats=Patients; (n)=number; CBR-Clinical Benefit Rate; p-values p&lt;0.05*, p&lt;0.01**, p&lt;0.001***]
Median PFS (months) for nVM for AI, SERD250, SERD500 & ‘all Ets combined’ were 5.4, 5.5, 11.0 & 5.5 respectively: for VM they were 2.9, 3.5, 5.5 & 3.2 respectively.
Median OS (months) for nVM for AI, SERD250, SERD500 & ‘all Ets combined’ was 24.2, 26.0, 35.4 & 25.4 respectively: for VM the figures were 22.8, 20.8, 26.4 & 22.0 respectively.Conclusions:1) In the 2nd line HR+ setting AI & Ful 250 both significantly increased PFS & OS in nVM versus VM. Longer PFS appears due to longer duration of control (DoCB) than increasing the number of patients responding (CBR).
2) Median OS for nVM ranged from 24 – 35 months versus 20.8-26.4 months for VM: for the majority of patients the 2nd line ET setting is not ‘immediately life threating’ and ET is therefore an option to consider.
3) These data on site of disease (nVM vs VM) contribute to the selection of which patients should receive endocrine mono- and which endocrine combination therapy (ie plus mTORi or CDK4/6i) in the second line setting.
Citation Format: Robertson JFR, Di Leo A, Johnston S, Chia S, Bliss J, Bradbury I, Campbell C. Meta-analyses of visceral versus non-visceral metastases treated by AI & SERD agents as 2nd line endocrine therapy (ET) for HR+ breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-13.