Etirinotecan pegol: An option for late-stage breast cancer?

摘要

Breast cancer is the most common malignancy in women in developed countries. Although breast cancer mortality has decreased in recent years, the disease is still the leading cause of cancer-related deaths in women. Most women who have recurrence of a primary breast cancer will have previously received taxane and anthracycline treatment in the adjuvant setting. Accordingly, very few treatment options are available for metastatic disease. Etirinotecan pegol (NKTR-102) is a long-acting inhibitor of topoisomerase I, which is an essential enzyme in mammalian cells, required for DNA replication, transcription, and repair. Irinotecan, another topoisomerase I inhibitor, is pharmacokinetically different to etirinotecan pegol, but both drugs are enzymatically converted to the biologically active metabolite SN38. As a monotherapy, the proportion of patients with metastatic breast cancer who achieve a response with irinotecan ranges from 5% to 23%. In The Lancet Oncology, Ahmad Awada and colleagues report data from a randomised phase 2 study assessing two dosing schedules of etirinotecan pegol (145 mg/m2 every 14 or 21 days) in 70 patients with metastatic breast cancer. Before treatment with etirinotecan pegol, patients had received taxane and a maximum of two chemotherapeutic regimens for their metastatic disease. Ten (29%) patients in each group had an objective response. Median progression-free survival (PFS) was 3.3 months for patients on the 14-day schedule and 5.6 months for those on the 21-day schedule; median overall survival was 8.8 months and 13.1 months for patients on the 14-day and 21-day schedules, respectively, with results thus favouring the 21-day schedule overall.