Abstract P6-16-02: Beta-adrenergic receptor blockers (BB) and increased progression free survival (PFS) in patients with advanced triple negative breast cancer (TNBC): A retrospective analysis of the ROSE/TRIO012 study
Authors: Spera G , Fresco R , Fung H , Dyck JRB , Pituskin E , Patterson I , Aspeslet L , Mackey JR 
Published: March 2017

Introduction: Recent retrospective studies suggest beta-adrenergic blocking drugs are associated with improved survival in patients with a wide range of cancers. Although limited and discordant data suggest that the use of BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC, which may be a more appropriate clinical scenario to evaluate anti-cancer effects of new treatment strategies.

We analyzed the relationship between BB use and clinical outcomes in the ROSE/TRIO012 study, a double-blinded multinational registration phase III trial that randomized 1,144 patients with HER2-negative advanced BC to receive first-line docetaxel in combination with ramucirumab (RAM) or placebo.

Objective: To explore the association between BB use and BC outcomes in patients participating in the ROSE/TRIO-012 trial.

Methodology: We retrospectively compared PFS,OS,Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) using the ITT population, in patients who received BB during the trial with those who did not receive them. PFS and OS were estimated using the Kaplan-Meier method. PFS and OS of both treatment groups were compared using the Log-Rank test. Cox proportional models were fitted to determine the association between BB, PFS and OS. ORR and CBR in both groups were compared using the Fisher's Exact Test.

Results: 153/1,144 (13%) patients received BB during the trial. Median PFS in patients treated with BB was 10.3 months, compared to 8.3 months in patients who did not receive them (HR 0.81; 95% CI 0.66-0.99; p=0.0379). In patients treated with BB only after enrolment (57/153, 37%) median PFS was 15.5 months vs. 8.3 months in patients with no BB (p=0.0005). In the subset of patients with TNBC, median PFS was 13 months if received BB compared to 5.2 months if no BB (HR 0.52; 95% CI 0.34-0.79; p=0.002). No difference in PFS was observed in patients with hormone receptor positive BC. The magnitude of PFS benefit in the RAM arm was similar as the whole ITT population (HR 0.73; 95% CI 0.57-0.94; p=0.014. If BB received only after enrolment HR 0.50; 95% CI 0.35-0.72; p=0.0003). The benefit of BB intake in PFS was independent of development of treatment-emergent hypertension (hypertension occurring within 42 days of first study drug administration; HR 0.92; 95% CI 0.73-1.15; p=0.476) but dependent on treatment arm (HR 0.86; 95% CI 0.74-0.99; p=0.037). The test for interactions between BB and treatment arm was not significant (p =0.276). No differences in OS, ORR or CBR were seen.

Conclusions: In this exploratory post-hoc analysis of the ROSE/TRIO012 study, BB intake was associated with a significant improvement in PFS compared to patients who did not receive them, particularly in patients with TNBC and patients not previously exposed to these drugs. Further evaluation of the BB intake on BC outcomes warrants evaluation in a prospectively-designed clinical trial.

Citation Format: Spera G, Fresco R, Fung H, Dyck JRB, Pituskin E, Patterson I, Aspeslet L, Mackey JR. Beta-adrenergic receptor blockers (BB) and increased progression free survival (PFS) in patients with advanced triple negative breast cancer (TNBC): A retrospective analysis of the ROSE/TRIO012 study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-02.