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Giredestrant for Estrogen Receptor–Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study

2024; Lippincott Williams & Wilkins; Volume: 42; Issue: 18 Linguagem: Inglês

10.1200/jco.23.01500

1527-7755

Miguel Martín, Elgene Lim, Mariana Chávez‐MacGregor, Aditya Bardia, Jiong Wu, Qingyuan Zhang, Zbigniew Nowecki, Felipe José Silva Melo Cruz, R. N. Safin, Sung‐Bae Kim, Christian Schem, Alberto J. Montero, Sarah Khan, Reeti Bandyopadhyay, Heather M. Moore, Mahesh Shivhare, Monika Patre, Jorge Martinalbo, Laura Roncoroni, Pablo Perez-Moreno, Joohyuk Sohn, G. Aguil, Marcos E. Alfie, Valeria Cáceres, Guillermo Lerzo, Sandra A. Ostoich, F. Boyle, Elgene Lim, Hayes Martin, Catherine Oakman, Felipe Melo Cruz, Fábio Franke, André Mattar, E.H. Silva, Katsuki Arima Tiscoski, Wei Chen, Wěi Li, Zhongsheng Tong, Jing Wang, Shaomeng Wang, X. Wang, Jiong Wu, Xiao‐Yuan Wu, Ju Yang, Q. Zhang, Till‐Oliver Emde, G. Gaffunder, Carsten Hielscher, Michael P. Lux, Christian Schem, Manfred Welslau, Claudia Schumacher, I. Kuchuk, T Peretz, Larisa Ryvo, R. Yerushalmi, Hee Dong Chae, Y.S. Chae, Seock‐Ah Im, Hwa Jung Kim, Jie‐Hyun Kim, S.-B. Kim, Jung Eun Lee, Y. H. Park, Joohyuk Sohn, Michał Jarząb, Monika Nowaczyk, Zbigniew Nowecki, Tadeusz Pieńkowski, Marek Z. Wojtukiewicz, Piotr J. Wysocki, E. Fomin, I. P. Ganshina, Nikolay Kislov, М. В. Копп, Н. В. Коваленко, Y. Makarova, Marina Matrosova, Р. В. Орлова, Artem Poltoratsky, Р. Р. Сафин, Р. А. Зуков, A. Wong, Yoon Sim Yap, M.A. Coccia-Portugal, Nicolaas H. Fourie, R. Khanyile, L. Schoeman, Ta‐Chung Chao, S.-T. Chen, Wei‐Pang Chung, Yin‐Hsun Feng, Yung‐Chang Lin, Thitiya Dejthevaporn, Napa Parinyanitikul, Chirawadee Sathitruangsak, Areewan Somwangprasert, Piyawan Tienchaianada, Ahmet Alacacıoğlu, Efnan Algın, Devrim Çabuk, Cengiz Demır, Umut Demırcı, Di̇lek Erdem, Sukru Hakan Gunduz, Murat Yıldırım, Siraj Ahmed Khan, Peter Schmid, I. Sandri, Olga Oikonomidou, Tameem Ansari, Apostolos Konstantis, S. Hrybach, A. Krochkin, O. Lipetska, D. Osinskii, S. Hrybach, A. Krochkin, O. Lipetska, D. Osinskii, J.C. Andersen, Michelina Cairo, Patrick Cobb, Venu Madhav Konala, Steve McCune, Alberto J. Montero, Debra A. Patt, Ines J Sanchez-Rivera, JJ Strain, KB Wendell,

HER2/EGFR in Cancer Research

PURPOSE To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor–positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455 ). METHODS Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone–releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). RESULTS At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA–evaluable patients (n = 232), the HR in patients with a detectable ESR1m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. CONCLUSION Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.