Abstract P5-14-01: A meta-analysis of clinical benefit rates for fulvestrant 500 mg versus alternative therapies for treatment of postmenopausal, estrogen receptor-positive advanced breast cancer
Authors: Robertson JFR , Zefei J , Di Leo A , Ohno S , Pritchard KI , Ellis M , Bradbury I , Campbell C 
Published: May 2016

Abstract
Background
Fulvestrant 500 mg has demonstrated improved efficacy vs fulvestrant 250 mg (time to progression [TTP]/progression free survival [PFS] and overall survival) in the treatment of postmenopausal women with advanced breast cancer (ABC). Few clinical trials have demonstrated a significant increase in clinical benefit rate (CBR) for one endocrine therapy (ET) over another for the treatment of ABC. This implies that TTP/PFS improvements have been achieved principally by prolonging time to developing acquired resistance. However, it would be beneficial to know whether CBR is also improved, indicating that more patients experience tumor remission. We performed a meta-analysis to determine if there was a difference in CBR between fulvestrant 500 mg and its comparators in randomized clinical trials (RCTs).
Methods
Five RCTs evaluating fulvestrant 500 mg were included: CONFIRM, China CONFIRM, FINDER1 and FINDER2 (vs fulvestrant 250 mg) as second-line ET and FIRST (vs anastrozole) as first-line ET. CBR was calculated as the proportion of patients experiencing a best objective response of stable disease for ≥24 weeks, complete response or partial response. Peto method was used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p values. Separate fixed effect (FE) models were constructed for first- and second-line data combined, and for second-line only data. For each model Tarone's test for heterogeneity assessed the assumption of constant trial effect.
Results
Unadjusted ORs for CBR from CONFIRM, FINDER1 and FINDER2, adjusted OR for China CONFIRM (as reported in the trial publications), and combined FE models are shown (Table).The OR (95% CI) of the FE model for all trials indicated that CBR was higher with fulvestrant 500 mg than with comparator treatments (OR: 1.34 [1.12-1.61]; FE p=0.001; Tarone's test p=0.91). When assessing second-line ET only, the OR was similar to the overall combined analysis.
ORs (95% CI) of CBR from individual trials and meta-analysis. nOR of CBR for fulvestrant 500 mg vs comparator (95% CI)First-lineFIRST2051.30 (0.72–2.38)Second-lineCONFIRM7361.28 (0.95–1.71)China CONFIRM2211.37 (1.04–1.80)FINDER1921.20 (0.53–2.74)FINDER2931.96 (0.84–4.54)Fixed effects modelFirst- and second-line combined13471.34 (1.12–1.61) FE p=0.001; Tarone's test p=0.91Second-line only11421.35 (1.11–1.63) FE p=0.002; Tarone's test p=0.81CBR, clinical benefit rate; CI, confidence interval; FE, fixed effects model; OR, odds ratio. Adjusted odds ratio and CI (as reported in the trial publications) are presented for China CONFIRM; unadjusted odds ratios and CIs are used for all other trials. FINDER1 and FINDER2 included fulvestrant 500 mg, 250 mg plus loading dose, and 250 mg treatment arms. Data shown for fulvestrant 500 mg versus 250 mg.
Conclusions
These data suggest that fulvestrant 500 mg is associated with a significant improvement in CBR of approximately 34% compared with comparator ETs (i.e. more tumors are placed into remission). This finding is consistent in both second- and first-line ET settings. We await the results of the Phase 3 FALCON first-line ET RCT to see if it supports this finding of increased CBR with fulvestrant 500 mg.
Citation Format: Robertson JFR, Zefei J, Di Leo A, Ohno S, Pritchard KI, Ellis M, Bradbury I, Campbell C. A meta-analysis of clinical benefit rates for fulvestrant 500 mg versus alternative therapies for treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-01.