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)

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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 25

Pages Range: 2975-2987

Journal Issue: 10

DOI: 10.1158/1078-0432.CCR-18-3160

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.

Authors with CRIS profile

Involved external institutions

Johns Hopkins Hospital United States (USA) (US) Medizinische Universität Wien Austria (AT) Hospital Clínic de Barcelona Spain (ES) Medizinische Universität Innsbruck Austria (AT) Hospital Clínico Universitario de Valencia Spain (ES) Vanderbilt University Medical Center United States (USA) (US) Rainier Therapeutics United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) Novartis AG Switzerland (CH) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US) Novartis Pharma S.A.S. France (FR) Hospital Network Antwerp / Ziekenhuis Netwerk Antwerpen (ZNA) Belgium (BE) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Dana–Farber Cancer Institute United States (USA) (US) MD Anderson Cancer Center Madrid Spain (ES) Kliniken Essen-Mitte Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE)

How to cite

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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