Abstract P1-07-09: Serum activin A and outcomes in HR+ /HER2- metastatic breast cancer patients treated with everolimus: Results from BOLERO-2
Authors: Ali SM , Chen D , Ali A , Krecko L , Leitzel K , Vasekar M , Nagabhairu V , Marks E , Polimera H , Richardson A , May M , He W , Patel P , Lavin M , Hofsess S , Sweetman R , Hortobagyi G , Baselga J , Lipton A 
Published: February 2018

Abstract
Background: Everolimus (EVE) plus exemestane (EXE) doubled progression-free survival (PFS) while maintaining quality of life versus EXE alone in postmenopausal women with hormone receptor positive (HR+), HER2-negative metastatic breast cancer (mBC) (BOLERO-2 phase 3; NCT00863655). Pretreatment serum activin A was previously reported as a prognostic factor in first-line hormone therapy (letrozole vs tamoxifen) (Novartis P025) and anti-HER2 mBC (lapatinib vs trastzmab) (CCTG MA.31) trials. Here we investigate the prognostic and predictive ability of activin A in BOLERO-2.
Methods: Activin A levels were determined on pretreatment serum samples using ELISA. Cox-proportional hazards model was used to assess the efficacy of EVE in the activin A low and high subgroups (median cut-point), and the prognostic effect of activin A on PFS and overall survival (OS).
Results: Baseline activin A levels were determined in 513 patients (71% of 725 BOLERO-2 patients randomized 2:1 to EVE+EXE or EXE). Predictive and prognostic signals are shown in the table below
Predictive and prognostic signalsPredictive/PrognosticEnd-pointAct-ivin ATreatmentNEventsMedian PFSHR (95% CI); p valuepredictivePFSHEXE93832.5 (1.5-2.8)-predictivePFSHEVE+EXE1631325.4 (4.1-6.8)0.46 (0.34 - 0.60); &lt;0.0001predictivePFSLEXE89774.2 (2.0 -5.4)-predictivePFSLEVE+EXE1681059.9 (8.1-12.5)0.38 (0.28 - 0.51); &lt;0.0001predictiveOSHEXE936820.1 (13.8-22.6)-predictiveOSHEVE+EXE16312917.7 (15.7-22.3)1.04 (0.78 - 1.40); 0.78predictiveOSLEXE8939NA (34.7-NA)-predictiveOSLEVE+EXE1687241.4 (36.4-NA)1.02 (0.69 - 1.50); 0.93prognosticPFSH 2562154.1 (2.9-4.2)-prognosticPFSL 2571826.9 (6.7-8.5)0.54 (0.45 - 0.66); &lt;0.0001prognosticOSH 25619718.0 (16.5-21.1)-prognosticOSL 25711142.3 (38.5-NA)0.34 (0.27 - 0.42); &lt;0.0001
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In multivariate analysis (including sensitivity to prior hormone therapy and visceral disease), activin A remained a significant independent prognostic factor for PFS and OS [HR 0.57 (0.46-0.69) and 0.34 (0.27-0.43), respectively].
Conclusions: Higher serum activin A was strongly associated with shorter PFS and OS in HR+/HER2- mBC patients. Everolimus was efficacious regardless of serum activin A level. These results are similar to our previous studies in phase 3 trials of letrozole-tamoxifen (Novartis P025), and HER2-targeted therapy, lapatinib vs trastuzmab (CCTG MA.31): pretreatment serum activin A was prognostic for outcome, but was not a predictive factor for treatment arm selection.
Citation Format: Ali SM, Chen D, Ali A, Krecko L, Leitzel K, Vasekar M, Nagabhairu V, Marks E, Polimera H, Richardson A, May M, He W, Patel P, Lavin M, Hofsess S, Sweetman R, Hortobagyi G, Baselga J, Lipton A. Serum activin A and outcomes in HR+ /HER2- metastatic breast cancer patients treated with everolimus: Results from BOLERO-2 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-09.