Giredestrant for Estrogen Receptor–Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study
Authors: Miguel Martín, Elgene Lim, Mariana Chavez-MacGregor, Aditya Bardia, Jiong Wu, Qingyuan Zhang, Zbigniew Nowecki, Felipe Melo Cruz, Rustem 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 Diego Pérez-Moreno, Joohyuk Sohn, G. Aguil, M. Alfie, V. Caceres, G. Lerzo, S. Ostoich, F. Boyle, E. Lim, H. Martin, C. Oakman, F.M. Cruz, F.A. Franke, A. Mattar, E.H. Silva, K. Tiscoski, W. Chen, W. Li, Z. Tong, J. Wang, S. Wang, X. Wang, J. Wu, X. Wu, J. Yang, Q. Zhang, T.-O. Emde, G. Gaffunder, C. Hielscher, M. Lux, C. Schem, M. Welslau, C. Schumacher, I. Kuchuk, T. Peretz, L. Ryvo, R. Yerushalmi, H. Chae, Y. S. Chae, S.-A. Im, H. J. Kim, J. H. Kim, S.-B. Kim, J. E. Lee, Y. H. Park, J. Sohn, M. Jarząb, M. Nowaczyk, Z. Nowecki, T. Pienkowski, M. Wojtukiewicz, P. Wysocki, E. Fomin, I. Ganshina, N. Kislov, M. Kopp, N. Kovalenko, Y. Makarova, M. Matrosova, R. Orlova, A. Poltoratsky, R. Safin, R. Zukov, A. Wong, Y.S. Yap, M. Coccia-Portugal, N. Fourie, R. Khanyile, L. Schoeman, T.-C. Chao, S.-T. Chen, W.-P. Chung, Y.-H. Feng, Y.-C. Lin, T. Dejthevaporn, N. Parinyanitikul, C. Sathitruangsak, A. Somwangprasert, P. Tienchaianada, A. Alacacioglu, E. Algin, D. Cabuk, C. Demir, U. Demirci, D. Erdem, Ş. Gündüz, M.E. Yildirim, S. Khan, P. Schmid, I. Sandri, O. Oikonomidou, T. Ansari, A. Konstantis, S. Hrybach, A. Krochkin, O. Lipetska, D. Osinskii, S. Hrybach, A. Krochkin, O. Lipetska, D. Osinskii, J.C. Andersen, M. Cairo, P. Cobb, V. Konala, S.L. McCune, A.J. Montero, D.A. Patt, I. Sanchez-Rivera, S. Strain, K. Wendell
Journal: Journal of Clinical Oncology (2024)

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.