As reported in JAMA Oncology by Debu Tripathy, MD, and colleagues, the phase III ATTAIN trial has shown no difference in overall survival with etirinotecan pegol vs physician’s choice of chemotherapy for patients with metastatic breast cancer and brain metastases.

The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with brain metastases However, this study represents one of the largest published trials dedicated to patients with breast cancer and brain metastases and may help to inform further research.

— Debu Tripathy, MD, and colleagues

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As noted by the investigators, the previously reported phase III BEACON trial showed no difference in overall survival with etirinotecan pegol vs physician’s choice of chemotherapy in patients with advanced breast cancer, but it did show a significant survival benefit in the subgroup of patients with preexisting, pretreated, and nonprogressive brain metastases.

Study Details

The open-label trial included 178 women from sites in 10 countries with a history of stable pretreated brain metastases who had disease progression while receiving chemotherapy in the metastatic setting. They were randomly assigned between March 2017 and November 2019 to receive etirinotecan pegol at 145 mg/m² every 21 days (n = 92) or physician’s choice of chemotherapy (n = 86) with eribulin (n = 34), vinorelbine (n = 17), gemcitabine (n = 16), nab-paclitaxel (n = 7), paclitaxel (n = 5), ixabepilone (n = 4), or docetaxel (n = 3) given in 21- or 28-day cycles. The primary endpoint was overall survival.

Overall Survival

Median overall survival was 7.8 months (95% confidence interval [CI] = 6.1–10.2 months) in the etirinotecan pegol group vs 7.5 months (95% CI = 5.8–10.4 months) in the chemotherapy group (hazard ratio [HR] = 0.90, 95% CI = 0.61–1.33, P = .60). Rates at 6 and 12 months were 63.4% vs 62.1% and 32.7% vs 31.2%.   

Overall median progression-free survival on blinded independent central review was 2.1 months (95% CI = 1.9–3.7 months) in the etirinotecan pegol group vs 1.9 months (95% CI = 1.8–2.0 months) in the chemotherapy group (HR = 0.59, 95% CI = 0.38–0.91, P = .02), including 2.8 vs 1.9 months (HR = 0.72, 95% CI = 0.45–1.16, P = .18) for non–central nervous system (CNS) metastases and 3.9 vs 3.3 months (HR = 0.59, 95% CI = 0.33–1.05, P = .07) for CNS metastases. Rates at 3 and 6 months were: 42.3% vs 26.2% and 14.8% vs 4.4% overall; 49.9% vs 32.8% and 32.1% vs 19.3% for non-CNS metastases; and 61.5% vs 51.8% and 23.3% vs 12.6% for CNS metastases.

Adverse Events

Grade 3 or 4 adverse events occurred in 56.7% of patients in the etirinotecan pegol group vs 63.6% of the chemotherapy group; the most common were diarrhea (13.3%), neutropenia (7.8%), and fatigue (6.7%) in the etirinotecan pegol group, and neutropenia (16.9%), decreased neutrophil count (9.1%), and fatigue and anemia (6.5% each) in the chemotherapy group. Serious adverse events occurred in 36.7% vs 31.2% of patients. Adverse events led to treatment discontinuation in 10% vs 1.3%. Adverse events led to death in three patients in the etirinotecan pegol group (3.3%) and no patients in the chemotherapy group.  

The investigators concluded, “The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with brain metastases However, this study represents one of the largest published trials dedicated to patients with breast cancer and brain metastases and may help to inform further research.”

Dr. Tripathy, of the Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Nektar Therapeutics. For full disclosures of the study authors, visit jamanetwork.com.