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Clinical Trial
. 2022 Jul 1;8(7):1047-1052.
doi: 10.1001/jamaoncol.2022.0514.

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial

Debu Tripathy  1 , Sara M Tolaney  2 , Andrew D Seidman  3 , Carey K Anders  4 , Nuhad Ibrahim  1 , Hope S Rugo  5 , Chris Twelves  6 , Véronique Diéras  7 , Volkmar Müller  8 , Yining Du  9 , Sue L Currie  9 , Ute Hoch  9 , Mary Tagliaferri  9 , Alison L Hannah  9 , Javier Cortés  10   11 ; ATTAIN Investigators
Collaborators, Affiliations
Clinical Trial

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial

Debu Tripathy et al. JAMA Oncol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Tripathy reported grants from Novartis and Pfizer as well as personal fees from OncoPep, AstraZeneca, Exact Sciences, Gilead, Novartis, Pfizer, and GlaxoSmithKline outside the submitted work. Dr Tolaney reported grants and personal fees from Nektar during the conduct of the study as well as grants from AstraZeneca, Eli Lilly, Merck, Genentech/Roche, Pfizer, Novartis, Gilead, Exelixis, BMS, Sanofi, Eisai, and SeaGen and personal fees from AstraZeneca, Eli Lilly, Merck, Genentech/Roche, Pfizer, Novartis, Gilead, Puma, Daiichi Sankyo, Silverback Therapeutics, G1 Therapeutics, Athenex, OncoPep, Kyowa Kirin Pharmaceuticals, Samsung Bioepsis, CytomX, Mersana Therapeutics, Certara, BMS, Eisai, Sanofi, 4D Pharma, OncoSec, BeyondSpring Pharmaceuticals, Chugai Pharma, OncXerna, Zymeworks, Zentalis, and SeaGen outside the submitted work. Dr Seidman reported personal fees from Nektar during the conduct of the study. Dr Anders reported grants from Nektar during the conduct of the study as well as grants from Puma, Eli Lilly, SeaGen, Tesaro, G-1 Therapeutics, Zion, Novartis, and Pfizer; personal fees from Genentech, Eisai, Ipsen, AstraZeneca, Immunomedics, Elucida, and Athenex; and royalties from UpToDate and Jones & Bartlett Publishing Company outside the submitted work. Dr Rugo reported grants from Nektar during the conduct of the study; and research support for clinical trials through the University of California from Pfizer, Merck, Novartis, Lilly, Roche, Odonate, Daiichi Sankyo, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, AstraZeneca, OBI, Gilead, and Ayala and honoraria from Puma, Samsung, and Napo outside the submitted work. Dr Twelves reported personal fees from Nektar during the conduct of the study and personal fees from Pfizer, Daiichi Sankyo, Eisai, Zentalis, and AstraZeneca and nonfinancial support from Roche outside the submitted work. Dr Diéras reported personal fees from Roche, Genentech, Novartis, Eli Lilly, MSD, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, SeaGen, Eisai, and Pierre Fabre outside the submitted work. Dr Müller reported personal fees from Nektar during the conduct of the study and personal fees from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, SeaGen, Onkowissen, high5 Oncology, and Medscape and honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, and SeaGen outside the submitted work. Dr Currie reported personal fees from Nektar Therapeutics during the conduct of the study. Drs Hoch and Tagliaferri reported being employed by Nektar Therapeutics. Dr Hannah reported personal fees from Nektar Therapeutics during the conduct of the study. Dr Cortés reported personal fees from Roche, Celgene, Cellestia, AstraZeneca, SeaGen, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Merck, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, Bioinvent, Gemoab, Gilead, Menarini, Zymeworks, Novartis, Eisai, Pfizer, and Samsung Bioepis; grants from Roche, Aria Pharmaceuticals, AstraZeneca, Baxalta, Bayer, Eisai, Guardant Health, Merck, PIQR, Puma, and Queen Mary University of London; and stock in Medsir outside the submitted work. No other disclosures were reported.

References

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