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Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial.

ABSTRACT: BACKGROUND:HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting. METHODS/DESIGN:The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (? 12?months/> 12?months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS. DISCUSSION:To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03910712 . Registered on 10 Apr. 2019.

SUBMITTER: Wang C

PROVIDER: S-EPMC7359576 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial.

Wang Changjun C Lin Yan Y Zhou Yidong Y Mao Feng F Zhu Hanjiang H Guan Jinghong J Zhang Xiaohui X Shen Songjie S Huang Xin X Chen Chang C Yao Ru R Zhao Jialin J Sun Qiang Q

BMC cancer 20200713 1

<h4>Background</h4>HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting.<h4>Methods/design</h4> ...[more]

PMID: 32660609

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Project description:BackgroundThe anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC.MethodsIn this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles.ResultsBetween May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively.ConclusionsIn women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

Project description:ObjectivePyrotinib and pertuzumab are effective treatment options for HER2-positive metastatic breast cancer (HER2+ MBC). Our study was to directly compare the efficacy and safety of pyrotinib plus trastuzumab (PyroH) and pertuzumab plus trastuzumab (HP) in patients with HER2+ MBC.MethodsWe conducted a retrospective examination of HER2+ MBC patients who received PyroH plus chemotherapy or HP plus chemotherapy between 2017 and 2022 at five institutions in China. Our primary endpoint was progression-free survival (PFS).ResultsThis study involved 333 patients, among which 161 received PyroH and 172 received HP. The utilization of PyroH as a first-line therapy for MBC was more prevalent among older patients, those with a shorter duration of disease-free interval, or those who had previously been treated with trastuzumab. Although in the first-line advanced treatment HP cohort showed numerically longer PFS (median PFS: 14.46 vs. 22.90 months, p=0.057), in the second-line or later treatments, there was no significant difference in PFS between the PyroH and HP groups (median PFS: 8.67 vs. 7.92 months, p=0.286). Despite HP showing a longer PFS in the overall cohort (median PFS: 9.30 vs. 13.01 months, p=0.005), it did not serve as an independent predictor of PFS in the multivariate analysis (HR 1.134, 95% CI 0.710-1.811, p=0.598). Without taxane, PyroH demonstrated a longer PFS than HP (median PFS: 10.12 vs. 8.15 months, p=0.017). PyroH group displayed a numerically longer median PFS in patients with brain metastases compared to the HP group, though not statistically significant (median PFS: 9.03 vs. 8.15 months, p=0.976). PyroH had higher incidence of grade 3/4 diarrhea (34.3% vs. 3.0%) but similar overall adverse events.ConclusionIn conclusion, PyroH is comparable in second-line or later treatment and during brain metastasis, even having superior efficacy without taxane in real-world setting. Toxicities were tolerable in both groups. (ClinicalTrials.gov: NCT05572645).

Project description:PurposeAndrogen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.MethodsEligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.ResultsOverall, 103 women were enrolled [median age 60 years (range 34-83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0-3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.ConclusionsEnzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. CLINICALTRIALS.Gov numberNCT02091960.

Dataset Information

Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial.

Publications

Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial.

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