Abstract PS11-24: Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for stage I-III HER2-positive breast cancer: Results of a single-arm pilot clinical trial
Authors: Jiang Jun 
Published: February 2021

Abstract
Aim: Pyrotinib is an irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptor 1 (HER1), HER2, and HER4, which exhibits well-tolerated antitumor activity in patients with HER2-postive metastatic breast cancer; however, its performance in neoadjuvant therapy remains uncertain. Thus, the efficacy and safety of neoadjuvant therapy of pyrotinib plus trastuzumab was estimated in patients with HER2-positive breast cancer in this pilot study.
Methods: Chinese female patients with stage I-III HER2-positive breast cancer were assigned to receive eight cycles of neoadjuvant pyrotinib (P) (400 mg) orally daily in combination with four cycles of epirubicin (E) (100 mg/m2), cyclophosphamide (C) (600 mg/m2) intravenously followed by four cycles of docetaxel (T) (100 mg/m2), trastuzumab (H) (8 mg/kg in the first load followed by 6 mg/kg) intravenously, once every three weeks, referred to as P + EC-TH, before definitive surgery. The primary endpoint was the proportion of patients who achieved a total pathological complete response (tpCR) in the breast and axilla (ypT0/is ypN0) in the intention-to-treat population. Safety was analyzed in patients who received at least one neoadjuvant treatment cycle according to the actual treatment received. This trial is registered with the Chinese Clinical Trial Registry (number: ChiCTR1900022293), and the follow up randomized, controlled phase III trial is ongoing.
Results: Between February 19, 2019, and May 25, 2019, 19 eligible patients were administrated pyrotinib neoadjuvant therapy with epirubicin plus cyclophosphamide, followed by docetaxel plus trastuzumab. A total of 18 patients completed the therapy and final surgery. The tpCR rate was 72.2% (95% CI: 46.5 - 90.3), and no recurrence or metastasis occurred during the short-term follow-up period. The objective response rate (ORR) was 100% (95% CI: 81.5 - 100) at the end of eighth cycle. The most common adverse events (AEs) were diarrhea and leukopenia in 17 of 19 patients (89.5 %). The most severe AEs were grade 4 leukopenia and neutropenia; however, no grade 5 AEs were reported.
Conclusions: This pilot study initially reported that neoadjuvant therapy of P + EC-TH improved the tpCR rate in HER2-positive operable or locally advanced breast cancer by approximately one time higher than EC-TH neoadjuvant therapy reported in other trials, with tolerable side effects. A subsequent randomized phase III clinical trial is warranted.
Table 1. Differences in the tpCR rates in the subgroupsP + EC-TH (n=18)CharacteristicNo.tpCR (No.)pCR rate (%)Patients181372.2Lymph-nodes statusPositive11872.7Negative7571.4Tumor size13266.72151173.330cTNMI3266.7II141071.4III11100.0HR statusPositive11761.1Negative7685.7Ki-67&lt;20%5240.0≥20%131184.6Pre-TILsLow5240.0Intermediate10880.0High33100.0Abbreviations: tpCR, total pathological complete response; cTNM, clinical TNM stage; HR, hormone receptor; Pre-TILs, previous treatment tumor infiltrating lymphocytes.
Table 2. P + EC-TH related AEs of all grades that occurred in all patients (n = 19)All GradesGrade 1Grade 2Grade 3Grades 4AENo. (%)No. (%)No. (%)No. (%)No. (%)Diarrhea17(89.5%)10(52.6%)14(73.7%)9(47.4%)0Leukopenia17(89.5%)10(52.6%)10(52.6%)6(31.6%)2(10.5%)Decreased hemoglobin16(84.2%)16(84.2%)6(31.6%)00Alopecia13(68.4%)6(31.6%)7(36.8%)00Vomiting12(63.2%)10(52.6%)2(10.5%)00Decreased appetite12(63.2%)12(63.2%)000Oral ulceration11(57.9%)11(57.9%)000Nausea10(52.6%)8(42.1%)2(10.5%)00Skin pigmentation10(52.6%)10(52.6%)000Neutropenia10(52.6%)3(15.8%)4(21.1%)3(15.8%)1(5.3%)Headache8(42.1%)8(42.1%)1(5.3%)00Increased ALT7(36.8%)5(26.3%)1(5.3%)3(15.8%)0Fatigue7(36.8%)7(36.8%)1(5.3%)00Weight loss6(31.6%)6(31.6%)000Increased AST5(26.3%)4(21.1%)1(5.3%)1(5.3%)0Muscle spasms5(26.3%)5(26.3%)000Thrombocytopenia5(26.3%)5(26.3%)000Rash3(15.8%)3(15.8%)000Dizziness2(10.5%)2(10.5%)000Cough2(10.5%)2(10.5%)000Hypokalemia2(10.5%)2(10.5%)000Upper respiratory tract infection2(10.5%)2(10.5%)000Increased total bilirubin2(10.5%)2(10.5%)000Stomachache2(10.5%)1(5.3%)1(5.3%)00Palpitation2(10.5%)2(10.5%)000Abbreviation: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase.
Citation Format: Jun Jiang. Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for stage I-III HER2-positive breast cancer: Results of a single-arm pilot clinical trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-24.