Etirinotecan Pegol Conveys No Benefit vs Chemotherapy for Patients With Metastatic Breast Cancer and Brain Metastases

Treatment with etirinotecan pegol yielded no statistically significant difference in outcomes compared to chemotherapy in patients with metastatic breast cancer and brain metastases, according to findings from the ATTAIN trial.

“Patients with breast cancer and brain metastases have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients,” explained Debu Tripathy, MD, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

The open-label, phase 3 ATTAIN trial enrolled 178 female patients with metastatic breast cancer and a history of stable pretreated brain metastases from 47 sites in 10 countries between March 7, 2017, and November 6, 2019, who proved unresponsive to chemotherapy in the metastatic setting. Patients were randomized to receive treatment with either etirinotecan pegol (n = 92) or chemotherapy (n = 86). The primary outcome of the study was overall survival (OS) with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), duration of response, and clinical benefit rate.

Treatment in both the etirinotecan pegol and chemotherapy arms yielded similar median OS (7.8 and 7.5 months, respectively; hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.61 to 1.33; P = 0.6). Median PFS for non–central nervous system metastases was 2.8 months in the etirinotecan pegol arm compared to 1.9 months with chemotherapy (HR, 0.72; 95% CI, 0.45 to 1.16; P = 0.18) The median PFS for  central nervous system metastases was 3.9 months with etirinotecan pegol vs 3.3 months in the chemotherapy arm (HR, 0.59; 95% CI, 0.33 to 1.05; P = .07)., respectively. Safety profiles between the groups were largely comparable.

The authors noted that though the trial results are not positive and run counter to the earlier BEACON trial’s findings, their study constitutes the most comprehensive published data on the topic to date and may be useful in guiding future research.

“There is a clear need for trials dedicated to this patient population or allowing for inclusion of patients with treated/untreated [brain metastases] in other studies and trials,” wrote Tripathy et al. “Results from this and other studies demonstrate the feasibility of trials in this population of patients with breast cancer and [brain metastases] and highlight the importance of confirming findings from subgroup analyses.”

Source:                                    

Tripathy D, Tolaney SM, Seidman AD, et al. Treatment with etirinotecan pegol for patients with metastatic breast cancer and brain metastases: Final results from the phase 3 ATTAIN randomized clinical trial. JAMA Oncol. 2022;8(7):1047-1052. doi:10.1001/jamaoncol.2022.0514