147950-156

Phase III trial of etirinotecan pegol (EP) versus Treatment of Physician’s Choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C): The BEACON study.

Subcategory: 
Category: 
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Abstract Number: 

1001

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 1001)
Author(s): 
Edith A. Perez, Ahmad Awada, Joyce O'Shaughnessy, Hope S. Rugo, Chris Twelves, Seock-Ah Im, Carol Zhao, Ute Hoch, Alison L. Hannah, Javier Cortes; Mayo Clinic, Jacksonville, FL; Jules Bordet Institute, Bruxelles, Belgium; Baylor Sammons Cancer Ctr US Onc, Dallas, TX; University of California, San Francisco, San Francisco, CA; LIMM, Leeds, United Kingdom; Seoul National University College of Medicine, Seoul, South Korea; Nektar Therapeutics, San Francisco, CA; Consultant, Sebastopol, CA; Vall D'Hebron University Hospital, Barcelona, Spain

Abstract Disclosures

Abstract: 

Background: EP is the first long-acting topoisomerase 1 inhibitor providing sustained levels of SN38. In Phase II, EP demonstrated a 29% ORR following a median of 2 prior regimens for aBC. BEACON study (NCT01492101) randomized (1:1) pts with aBC and progressive disease following A,T and C to EP (145 mg/m2q3w over 90 minutes) or TPC (any of 7 cytotoxics). Methods: Eligible pts had any ER/HER2 and ECOG 0-1; stable brain metastases were allowed. 852 pts enrolled over 20 months and reached target for events in Dec2014. The choice of TPC: eribulin 40%, vinorelbine 23%, gemcitabine 18%, taxane 15%, ixabepilone 4%. Primary efficacy endpoint was overall survival (OS) by 2-sided log-rank test stratified by region, prior eribulin and receptor status; the study had 90% power to detect a target Hazard Ratio (HR) of 0.77. Circulating tumor cells (CTCs) were isolated in ~80% of pts and analyzed for target-specific pharmacodynamic biomarkers. This is the first presentation of these data. Results: EP provided a 2.1 month improvement in median OS over TPC (12.4 vs 10.3 months; HR 0.87, p = 0.08). In a pre-specified subgroup of 67 pts with brain metastases, EP showed an improvement of 5.2 months in median OS (10.0 vs 4.8 months; HR 0.51, p < 0.01); the proportion of pts with brain metastases alive at 12-mo survival was higher with EP (44.4% vs 19.4%). Similarly, in pts with liver metastases (n = 456) median OS improved with EP (10.9 vs 8.3 months; HR 0.73, p = 0.002). Grade (G) ≥ 3 AEs were lower with EP (48%) than TPC (63%). Common G ≥ 3 AE with EP: diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%); TPC: neutropenia (30.5%), anemia (4.7%) and dyspnea (4.4%). Severe neuropathy: 3.7% of pts (TPC) vs 0.5% (EP). Alopecia was less with EP (10% vs 23%). Data on efficacy in CTC biomarker defined sub-groups (TOP1, TOP2) will be presented. Conclusions: EP provided a clinically meaningful benefit to pts with late-stage aBC, although this did not reach statistical significance. In pts with brain metastases, median OS doubled; improved survival was also seen in other pt subsets. Toxicity with EP was less than with TPC. Clinical trial information: NCT01492101