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Phase II trial of neoadjuvant letrozole and lapatinib in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer [Neo-ALL-IN]: Highlighting the TILs, ER expressional change after neoadjuvant treatment, and FES-PET as potential significant biomarkers.
- Source :
- Cancer Chemotherapy & Pharmacology; Oct2016, Vol. 78 Issue 4, p685-695, 11p
- Publication Year :
- 2016
-
Abstract
- <bold>Purpose: </bold>Neo-ALL-IN (NCT 01275859) is a single-center, phase II study aimed to evaluate the efficacy and safety profiles of neoadjuvant letrozole plus lapatinib, as well as potential biomarkers, in postmenopausal women with ER- and HER2-positive (ER+HER2+) breast cancer.<bold>Methods: </bold>Postmenopausal ER+HER2+ breast cancer of stages II-III was eligible. Daily 2.5 mg letrozole plus 1500 mg lapatinib were administered for 18-21 weeks before surgery. Clinical responses were assessed by palpation with caliper, breast ultrasonography, mammogram, and/or MRI. Biologic samples were collected for biomarker analyses at three time points (baseline, day 14, and before surgery). Baseline fluorine-18 fluorodeoxyglucose and fluorine-18 fluoroestradiol PET-CT scans were performed.<bold>Results: </bold>Among 24 patients enrolled, 17 (70.8 %) completed planned neoadjuvant treatment, whereas 7 prematurely terminated the treatment and proceeded to surgery because of toxicity or progression; 2 patients showed definite progression, and 2 showed clinical regrowth by palpation regardless of minimal response. All patients eventually underwent breast cancer surgery. Toxicities were generally mild mostly within grades 1-2 except prolonged or recurrent grade 3 liver toxicities in 3 patients (13.6 %) regardless of sequential dose reduction, which finally led to discontinuation of treatment. The overall clinical response rates were 62.5 % (n = 15) including 1 CR in breast. However, no pathologic CR (ypT0-is N0) was achieved. SUVmax lower than 5.5 in baseline FES PET-CT (p = 0.007), baseline TILs over 20 % (p = 0.026), and decreased IHC ER Allred score after neoadjuvant treatment (p = 0.021) were significantly associated with adverse clinical response.<bold>Conclusions: </bold>When this chemo-free, combination neoadjuvant therapy with letrozole and lapatinib is given for Asian postmenopausal ER+HER2+ breast cancer, TILs, change of ER expression following neoadjuvant treatment, and SUVmax in baseline FES-PET are to be considered potential biomarkers in these patients. [ABSTRACT FROM AUTHOR]
- Subjects :
- HORMONE receptor positive breast cancer
LETROZOLE
LAPATINIB
POSTMENOPAUSE
DRUG efficacy
MEDICATION safety
BIOMARKERS
CANCER treatment
THERAPEUTICS
ANTINEOPLASTIC agents
ASIANS
BREAST tumors
CELL receptors
CLINICAL trials
COMBINED modality therapy
COMPARATIVE studies
HETEROCYCLIC compounds
LYMPHOCYTES
MASTECTOMY
RESEARCH methodology
MEDICAL cooperation
ORGANIC compounds
PROTEINS
RESEARCH
POSITRON emission tomography
EVALUATION research
LYMPHOCYTE count
Subjects
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 78
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 118414824
- Full Text :
- https://doi.org/10.1007/s00280-016-3107-6