Dataset Information

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).

ABSTRACT:

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 whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting.Patients and Methods: 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% of 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 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⁺ early breast cancer.

SUBMITTER: Mayer IA

PROVIDER: S-EPMC6522303 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

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 Ingrid A IA Prat Aleix A Egle Daniel D Blau Sibel S Fidalgo J Alejandro Pérez JAP Gnant Michael M Fasching Peter A PA Colleoni Marco M Wolff Antonio C AC Winer Eric P EP Singer Christian F CF Hurvitz Sara S Estévez Laura García LG van Dam Peter A PA Kümmel Sherko S Mundhenke Christoph C Holmes Frankie F Babbar Naveen N Charbonnier Laure L Diaz-Padilla Ivan I Vogl Florian D FD Sellami Dalila D Arteaga Carlos L CL

Clinical cancer research : an official journal of the American Association for Cancer Research 20190205 10

<h4>Purpose</h4>Addition of alpelisib to fulvestrant significantly extended progression-free survival in <i>PIK3CA</i>-mutant, hormone receptor-positive (HR<sup>+</sup>) 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<sup>+</sup> advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant se ...[more]

PMID: 30723140

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Project description:The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor-positive (hr+), human epidermal growth factor receptor 2-positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib-letrozole, letrozole, anastrozole, or trastuzumab-anastrozole as first-line treatment. Clinical inputs for lapatinib-letrozole and letrozole were taken from the EGF30008 trial (NCT00073528). Clinical inputs for anastrozole and trastuzumab-anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer's price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan's Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.Quality-adjusted life years gained with lapatinib-letrozole were 0.236 compared with trastuzumab-anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib-letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab-anastrozole. Results from the societal perspective were similar.In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib-letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab-anastrozole.

Dataset Information

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).

Purpose

Results

Conclusions

Publications

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).

Similar Datasets

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