Etirinotecan Pegol Active in Patients With Previously Treated Metastatic Breast Cancer
Etirinotecan pegol is a topoisomerase-I inhibitor designed to provide prolonged tumor cell exposure to the active metabolite of irinotecan. In a phase II study reported in The Lancet Oncology, Ahmad Awada, MD, of Jules Bordet Institute, Université Libre de Bruxelles, and colleagues examined every-2-week and every-3-week regimens of etirinotecan pegol in patients with previously treated metastatic breast cancer. On the basis of the study findings, the every-3-week regimen was advanced to phase III testing.
Study Details
In this open-label trial, 70 patients who had received taxane therapy and no more than two previous chemotherapy regimens for metastatic breast cancer and had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were randomly assigned to etirinotecan pegol at 145 mg/m² every 14 days (n = 35) or every 21 days (n = 35). The primary endpoint was confirmed objective response as defined by RECIST (version 1.0).
The 14-day and 21-day groups were generally balanced for age (median, 53 and 56 years), ECOG performance status (1 in 57% and 63%), menopausal status (postmenopausal in 71% and 83%), time from initial diagnosis (median, 4.0 and 5.4 years), receptor status (estrogen receptor–positive in 60% and 57%, progesterone receptor–positive in 31% and 37%, HER2-positive in 9% and 6%, and triple-negative in 31% and 29%), visceral disease (80% and 91%), median number of cytotoxic regimens in the metastatic setting (one and two), and previous systemic treatments (eg, cytotoxic neoadjuvant or adjuvant therapy in 77% and 69%, anthracycline in 89% in both, anthracycline/taxane in 66% and 60%, and capecitabine in 26% and 29%).
Response Rates
Of the 70 patients, 20 (29%, 95% confidence interval [CI] = 18.4–40.6) achieved an objective response, including complete response in 2 (3%) and partial response in 18 (26%). Response was observed in 10 patients in the 14-day group (29%, 95% CI = 14.6–46.3), including 8 partial responses and 2 complete responses, and in 10 in the 21-day group (29%, 95% CI = 14.6–46.3), all with partial response.
Median progression-free survival was 3.3 months in patients on the 14-day schedule and 5.6 months in patients on the 21-day schedule, and median overall survival was 8.8 vs 13.1 months; 6-month overall survival was 57.1% vs 82.9%, and 1-year overall survival was 42.9% vs 51.4%. Exploratory subgroup analyses indicated that the 21-day regimen was associated with better efficacy outcomes among women with triple-negative disease and those who had received prior anthracycline/taxane or anthracycline/taxane/capecitabine treatment.
Toxicities
Grade 3 or higher adverse events occurred in 54% of the 14-day group and 52% of the 21-day group and serious adverse events occurred in 51% vs 43%. The most common grade 3 or higher adverse events were delayed diarrhea (20% vs 23%), fatigue (14% vs 9%), neutropenia (11% vs 11%), and dehydration (9% vs 11%). In total, 20% of patients discontinued treatment due to drug-related toxicity. There were two possible drug-related deaths (acute renal failure and septic shock) in the 14-day group. Other drug-related serious adverse events reported by more than one patient included diarrhea (17% vs 11%), dehydration (6% vs 11%), nausea (6% vs 0%), and vomiting (6% vs 0%).
The investigators concluded, “On the basis of the overall clinical data, pharmacokinetics, and tolerability profile, etirinotecan pegol 145 mg/m² every 21 days has been selected for a phase III trial against treatment of physician’s choice in patients with advanced breast cancer.”
The study was funded by Nektar Therapeutics.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
