A phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NeO-ORB)

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Mayer IA, Prat A, Egle D, Blau S, Alejandro Perez Fidalgo J, Gnant M, Fasching P, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estevez LG, Van Dam PA, Kummel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL
Zeitschrift: Clinical Cancer Research
Jahr der Veröffentlichung: 2019
Band: 25
Heftnummer: 10
Seitenbereich: 2975-2987
ISSN: 1078-0432


Abstract

Purpose: Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA-mutant, hormone receptor–positive (HR
þ
) advanced/metastatic breast cancer in the phase III SOLAR-1 study. The combination of alpelisib and letrozole also had promising activity in phase I studies of HR
þ
advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting. Patients and Methods: Postmenopausal women with HR
þ
, human epidermal growth factor receptor 2-negative, T1c-T3 breast cancer were assigned to the PIK3CA-wild-type or PIK3CA-mutant cohort according to their tumor PIK3CA status, and randomized (1:1) to 2.5 mg/day letrozole with 300 mg/day alpelisib or placebo for 24 weeks. Primary endpoints were objective response rate (ORR) and pathologic complete response (pCR) rate for both PIK3CA cohorts. Results: In total, 257 patients were assigned to letrozole plus alpelisib (131 patients) or placebo (126 patients). Grade 3 adverse events (5% of patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculopapular rash (8%). The primary objective was not met; ORR in the alpelisib versus placebo arm was 43% versus 45% and 63% versus 61% in the PIK3CA-mutant and wild-type cohorts, respectively. pCR rates were low in all groups. Decreases in Ki-67 were similar across treatment arms and cohorts. In PIK3CA-mutant tumors, alpelisib plus letrozole treatment induced a greater decrease in phosphorylated AKT versus placebo plus letrozole. Conclusions: In contrast to initial results in advanced/metastatic disease, addition of alpelisib to 24-week neoadjuvant letrozole treatment did not improve response in patients with HR
þ
early breast cancer.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

Dana–Farber Cancer Institute
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Hospital Clínic de Barcelona
Hospital Clínico Universitario de Valencia
Hospital Network Antwerp / Ziekenhuis Netwerk Antwerpen (ZNA)
Johns Hopkins Hospital
Kliniken Essen-Mitte
MD Anderson Cancer Center Madrid
Medizinische Universität Innsbruck
Medizinische Universität Wien
Novartis AG
Novartis Pharma S.A.S.
Rainier Therapeutics
Universitätsklinikum Schleswig-Holstein (UKSH)
University of California Los Angeles (UCLA)
University of Texas Southwestern Medical Center (UT Southwestern)
Vanderbilt University Medical Center


Zitierweisen

APA:
Mayer, I.A., Prat, A., Egle, D., Blau, S., Alejandro Perez Fidalgo, J., Gnant, M.,... Arteaga, C.L. (2019). A phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NeO-ORB). Clinical Cancer Research, 25(10), 2975-2987. https://dx.doi.org/10.1158/1078-0432.CCR-18-3160

MLA:
Mayer, Ingrid A., et al. "A phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NeO-ORB)." Clinical Cancer Research 25.10 (2019): 2975-2987.

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Zuletzt aktualisiert 2019-03-06 um 11:23