Abstract P1-14-02: Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In]: First efficacy and safety report
Authors: Park Ji Hyun , Kang Myoung Joo , Ahn Jin-Hee , Kim Jeong Eun , Jung Kyung Hae , Gong Gyung-Yub , Lee Hee Jin , Son Byung-Ho , Ahn Sei-Hyun , Kim Hak-Hee , Shin Hee Jung , Moon Dae-Hyuk , Kim Sung-Bae 
Published: May 2015

Abstract
Purpose Neo-ALL-In (NCT 01275859) is a single center, prospective study aimed to evaluate the recruitment feasibility, efficacy and safety profiles as well as biologic features of neoadjuvant letrozole plus lapatinib in postmenopausal women with ER and HER2 positive breast cancer.
Methods Postmenopausal women with stage IIA to IIIB ER and HER-2 positive breast cancer were eligible. Patients received combination therapy of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily for 18-21 weeks before surgery. Clinical responses were assessed by clinical palpation, ultrasonography (US), mammography and/or MRI. Tissue and/or blood samples were collected for analysis of biomarkers at three time points (baseline, day 15, and before surgery). Baseline Fluorine-18 Fluorodeoxyglucose (18F-FDG) and Fluorine-18 Fluoroestradiol (18F-FES) PET-CT imagings were obtained.
Results Among twenty-four patients enrolled, 22 patients underwent surgery while 1 patient is currently on neoadjuvant therapy and the other patient is waiting for surgery. Among 22 patients completed surgery, 16 patients (72.7%) completed planned neoadjuvant letrozole and lapatinib, whereas 3 patients (13.6%) prematurely terminated the treatment and proceeded to surgery due to minimal clinical response or progression. Except grade 3 liver toxicities revealed in 3 patients (13.6%), which resulted in sequential dose reduction and discontinuation, adverse events were mainly grades 1 to 2 (Skin, 83.3%; GI, 77.3%), and these were generally tolerable with excellent compliance. Overall clinical response rates including complete and partial response was 72.7% (n=16), and pathologic complete response in breast (pCR; ypT0-is) was 4.5% (n=1).
Clinical and pathologic responses of 22 patients by assessment modalitiesTotal (N=22, %)Clinical palpationUSMammographyMRpathologic response in breast (ypT0-is)pathologic response in breast and lymph nodes (ypT0-is N0)Overall responseCR1 (4.5)0 (0.0)0 (0.0)1 (4.5)1 (4.5)0 (0.0)1 (4.5)PR17 (77.3)12 (54.5)9 (40.9)9 (40.9)11 (50.0)15 (68.215 (68.2)No change3 (13.6)9 (40.9)13 (59.1)5 (22.7)9 (40.9)7 (31.8)4 (18.2)PD1(4.5)1 (4.5)0 (0.0)1 (4.5)1 (4.5)0 (0.0)2 (9.1)Not available/evaluable0 (0.0)0 (0.0)0 (0.0)6 (27.3)0 (0.0)0 (0.0)0 (0.0)CR, complete response; PR, partial response; PD, progressive disease; US, ultrasonography
In analyses of biomarkers thus far, 81.8% of patients showed stationary expression of HER-2, 54.5% of patients showed decrease in Ki-67 expression, and 27.3% of patients showed increase in ER expression from baseline to surgery by immunothistochemistry (IHC) staining. Decreased expression of ER after surgery by IHC staining was significantly correlated with poor clinical response (p=0.004). However, no significant differences in baseline SUVmax in FDG-PET were found between responders and non-responders (8.8 VS 10.7, p=0.53).
Conclusion This chemo-free combination neoadjuvant therapy was feasible, with comparable efficacy outcomes and manageable toxicities profiles. Updated data on 18F-FES PET-CT and biomarkers will be provided.
Citation Format: Ji Hyun Park, Myoung Joo Kang, Jin-Hee Ahn, Jeong Eun Kim, Kyung Hae Jung, Gyung-Yub Gong, Hee Jin Lee, Byung-Ho Son, Sei-Hyun Ahn, Hak-Hee Kim, Hee Jung Shin, Dae-Hyuk Moon, Sung-Bae Kim. Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In]: First efficacy and safety report [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-14-02.