Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases

TY - JOUR

T1 - Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases

T2 - Final Results From the Phase 3 ATTAIN Randomized Clinical Trial

AU - Tripathy, Debu

AU - Tolaney, Sara M

AU - Seidman, Andrew D

AU - Anders, Carey K

AU - Ibrahim, Nuhad

AU - Rugo, Hope S

AU - Twelves, Chris

AU - Diéras, Véronique

AU - Müller, Volkmar

AU - Du, Yining

AU - Currie, Sue L

AU - Hoch, Ute

AU - Tagliaferri, Mary

AU - Hannah, Alison L

AU - Cortés, Javier

AU - ATTAIN Investigators

PY - 2022/7/1

Y1 - 2022/7/1

N2 - IMPORTANCE: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM.OBJECTIVE: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial.DESIGN, SETTING, AND PARTICIPANTS: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019.INTERVENTIONS: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel).MAIN OUTCOMES AND MEASURES: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate.RESULTS: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable.CONCLUSIONS AND RELEVANCE: 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 BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02915744.

AB - IMPORTANCE: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM.OBJECTIVE: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial.DESIGN, SETTING, AND PARTICIPANTS: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019.INTERVENTIONS: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel).MAIN OUTCOMES AND MEASURES: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate.RESULTS: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable.CONCLUSIONS AND RELEVANCE: 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 BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02915744.

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Brain Neoplasms/drug therapy

KW - Breast Neoplasms/pathology

KW - Female

KW - Heterocyclic Compounds, 4 or More Rings/adverse effects

KW - Humans

KW - Middle Aged

KW - Polyethylene Glycols/adverse effects

U2 - 10.1001/jamaoncol.2022.0514

DO - 10.1001/jamaoncol.2022.0514

M3 - SCORING: Journal article

C2 - 35552364

VL - 8

SP - 1047

EP - 1052

JO - JAMA ONCOL

JF - JAMA ONCOL

SN - 2374-2437

IS - 7

ER -