S'abonner

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study - 30/08/23

Doi : 10.1016/S1470-2045(23)00268-1 
Sara A Hurvitz, ProfMD a, b, , Aditya Bardia, MD MPH c, Vanesa Quiroga, MD PhD d, e, Yeon Hee Park, ProfMD PhD f, Isabel Blancas, MD PhD d, g, h, José Luis Alonso-Romero, MD PhD d, i, Aleksandr Vasiliev, MD j, Hryhoriy Adamchuk, MD k, Marcelo Salgado, MD PhD l, Denise A Yardley, MD m, Oleksandr Berzoy, MD n, Pilar Zamora-Auñón, MD d, o, David Chan, MD p, Gonzalo Spera, MD MSc q, Cloris Xue, PhD r, Erika Ferreira, MEng s, Tanja Badovinac Crnjevic, MD MSc t, Pablo Diego Pérez-Moreno, MD u, Vanesa López-Valverde, PhD t, Jutta Steinseifer, MD PhD t, Tharu M Fernando, PhD u, Heather M Moore, PhD u, Peter A Fasching, ProfMD v
on behalf of the

coopERA Breast Cancer study group

  Investigators are listed in the Supplementary Material

a Breast Cancer Clinical Trials Program, Division of Hematology-Oncology, David Geffen School of Medicine, Clinical Research Unit, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA 
b Fred Hutchinson Cancer Center, Seattle, WA, USA 
c Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 
d GEICAM Spanish Breast Cancer Group, San Sebastián de los Reyes, Madrid, Spain 
e Catalan Institute of Oncology Badalona, Barcelona, Spain 
f Samsung Medical Center, Seoul, Republic of Korea 
g Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada, Granada, Spain 
h Medicine Department, Granada University, Granada, Spain 
i Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain 
j NSHI Road Clinical Hospital of JSC Russian Railways, Saint Petersburg, Russia 
k Communal Enterprise Kryvyi Rih Oncology Dispensary, Kryvyi Rih, Ukraine 
l Hospital do Câncer de Pernambuco, Recife, Brazil 
m Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, USA 
n Communal Non-profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council, Odesa, Ukraine 
o Hospital Universitario La Paz, Madrid, Spain 
p Torrance Memorial Hunt Cancer Center, Torrance, CA, USA 
q Translational Research in Oncology (TRIO), Montevideo, Uruguay 
r F Hoffmann-La Roche, Toronto, ON, Canada 
s Roche Products, Welwyn Garden City, UK 
t F Hoffmann-La Roche, Basel, Switzerland 
u Genentech, South San Francisco, CA, USA 
v University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany 

* Correspondence to: Prof Sara A Hurvitz, Fred Hutchinson Cancer Center, Seattle 98109, WA, USA Fred Hutchinson Cancer Center Seattle WA 98109 USA

Summary

Background

The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer.

Methods

In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a–c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0–1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1–14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1–21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete.

Findings

Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0–68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0–67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was –75% (95% CI –80 to –70) with giredestrant and –67% (–73 to –59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3–4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction).

Interpretation

Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials.

Funding

F Hoffmann-La Roche.

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© 2023  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Publié par Elsevier Masson SAS. Tous droits réservés.
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P. 1029-1041 - septembre 2023 Retour au numéro
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