No Significant Survival Improvement With Etirinotecan Pegol vs Physician’s Choice in Heavily Pretreated Advanced Breast Cancer
In the phase III BEACON trial reported in The Lancet Oncology, Perez et al found that etirinotecan pegol was not associated with a significant increase in overall survival compared with physician’s choice of treatment in women with locally recurrent or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. Etirinotecan pegol is designed to prolong exposure to and reduce toxicity of the active metabolite of irinotecan (SN38). Benefit was observed in some patient subgroups.
Study Details
In this open-label trial, 852 women from 135 sites in 11 countries who had previously received an anthracycline, a taxane, and capecitabine and two to five regimens for advanced disease were randomly assigned between December 2011 and August 2013 to receive etirinotecan pegol at 145 mg/m² as a 90-minute intravenous infusion every 3 weeks (n = 429) or single-drug treatment of physician’s choice (n = 423).
The most common treatments in the physician’s choice group were eribulin (Halaven, 40%), vinorelbine (23%), gemcitabine (17%), and nab-paclitaxel (Abraxane) (8%). The primary endpoint was overall survival in the intent-to-treat population.
Patients had a median age of 55 years, most were treated in North America or Europe, 65% had hormone receptor–positive and HER2-negative disease, and 28% had triple-negative disease. The most common metastatic sites were bone (57%), liver (53%–54%), and lungs (36%–40%), with 4% of patients in both groups having stable brain metastasis.
Overall Survival
Median follow-up was 21.1 months in the etirinotecan pegol group and 21.7 months in the physician’s choice group. Median overall survival was 12.4 months (95% confidence interval [CI] = 11.0–13.6 months) in the etirinotecan pegol group vs 10.3 months (95% CI = 9.0–11.3 months) in the physician’s choice group (hazard ratio [HR] = 0.87, P = .084).
In subgroup analysis, hazard ratios significantly favored etirinotecan pegol in patients with liver (HR = 0.73, 95% CI = 0.59–0.89) and brain metastasis (HR = 0.51, 95% CI = 0.30–0.86) and in those with more than two metastatic sites (HR = 0.77, 95% CI = 0.62–0.95); a near-significant hazard ratio was observed in patients with hormone receptor–positive/HER2-negative disease (HR = 0.83, 95% CI = 0.69–1.00). Median progression-free survival was 2.4 vs 2.8 months (HR = 0.93, P = .30).
Toxicities
Serious adverse events occurred in 30% vs 32% of patients. Grade ≥ 3 adverse events occurred in 48% vs 63% (P < .0001), with the most common being diarrhea (10% vs 1%), neutropenia (10% vs 31%), and peripheral neuropathy (< 1% vs 4%). Death due to treatment-related adverse events occurred in three patients in the etirinotecan pegol group (pneumonia, myelodysplastic syndrome, and acute renal failure) and two patients in the physician’s choice group (neutropenic sepsis and septic shock).
The investigators concluded: “This trial did not demonstrate an improvement in overall survival for etirinotecan pegol compared to treatment of physician’s choice in patients with heavily pre-treated advanced breast cancer. The toxicity profile noted in the etirinotecan pegol group differed from that in the control group. In view of the frequency of cross-resistance and overlapping toxicities noted with many available drugs and the need for effective drugs in highly refractory disease, etirinotecan pegol may warrant further research in some subgroups of patients.”
Edith A. Perez, MD, of Mayo Clinic, Jacksonville, is the corresponding author for the Lancet Oncology article.
The study was funded by Nektar Therapeutics. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
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