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Title
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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)
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Author
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Abstract
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| Purpose: Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA-mutant, hormone receptor-positive (HR+) 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+ advanced/metastatic breast cancer. NEO-ORB aimed to determine if addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting. Experimental Design: Postmenopausal women with HR+, 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% patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculo-papular rash (8%). The primary objective was not met; ORR in the alpelisib vs. placebo arm was 43% vs. 45% and 63% vs. 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 vs. 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+ early breast cancer. |
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Language
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English
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Source (journal)
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Clinical cancer research. - Philadelphia, Pa, 1995, currens
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Publication
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Philadelphia, Pa
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Association for Cancer Research
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2019
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ISSN
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1078-0432
[print]
1557-3265
[online]
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DOI
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10.1158/1078-0432.CCR-18-3160
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Volume/pages
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25
:10
(2019)
, p. 2975-2987
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ISI
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000468064200007
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Pubmed ID
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30723140
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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