Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

Yi Li; Chengcheng Gong; Qianyi Lu; Zhaochun Zhou; Ting Luo; Wei Li; Gang Li; Rui Ge; Fei Xu; Biyun Wang

doi:10.3389/fonc.2020.00271

Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

Front Oncol. 2020 Mar 3:10:271. doi: 10.3389/fonc.2020.00271. eCollection 2020.

Authors

Yi Li¹, Chengcheng Gong¹, Qianyi Lu², Zhaochun Zhou³, Ting Luo⁴, Wei Li⁵, Gang Li⁶, Rui Ge⁷, Fei Xu², Biyun Wang¹

Affiliations

¹ Department of Medical Oncology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
² The State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
³ Huangpu Branch of Shanghai Ninth People's Hospital, Shanghai, China.
⁴ Department of Head, Neck and Mammary Gland Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Medical Oncology, Jiangsu Province Hospital, Nanjing, China.
⁶ Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, China.
⁷ Huadong Hospital Affiliated to Fudan University, Shanghai, China.

Abstract

Introduction: Combination of trastuzumab (T) and lapatinib (L) has been showed to significantly improve the prognosis of HER2+ heavily pretreated metastatic breast cancer (MBC). Whether TL combined chemotherapy (TLC) can further improve the efficacy in HER2+ MBC remains to be further studied. The aim of the study was to report the first real-world data of TLC in HER2+ MBC, including the efficacy, safety and treatment patterns. Methods: Patients with HER2+ MBC treated with TLC in 5 institutions of China from September 2013 to July 2019 were included. Progression free survival (PFS), objective response rate (ORR), overall survival (OS), toxicity profile and treatment pattern were reported. Results: A total of 285 patients were included. 88.8% were exposed to trastuzumab and 49.2% received 2 or more lines of systematic therapy before TLC previously. The most common chemotherapy regimens combined with TL were capecitabine (40.7%) and vinorelbine (21.4%) and almost 1/3 received maintenance treatment after TLC. Median PFS was 10.9 months while patients received TLC as first line treatment showed longest median PFS of 20.7 months. Patients pretreated with trastuzumab showed a median PFS of 10.2 months. In patients who pretreated with trastuzumab, the continuation of trastuzumab on the basis of standard lapatinib plus capecitabine had a median PFS of 11.3 months. TL combined with capecitabine or vinorelbine showed no significant difference in median PFS, though TL combined with capecitabine had numerically prolongation (11.4 vs. 8.5 months, p = 0.231). Patients had brain metastasis (BM) also showed a median PFS (intracranial and extracranial lesions considered) of 10.6 months. Lines of systematic metastatic treatment was an independent predictive factor of PFS. The median OS was not reached. Two hundred and seventy seven patients were included in ORR analysis. ORR was 42.6%. Toxicities of triplet combinations were tolerable and the most common grade 3 and 4 adverse events were neutropenia (16.8%). Conclusions: TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04001634.

Keywords: chemotherapy; human epidermal growth factor receptor 2 positive; lapatinib; metastatic breast cancer; trastuzumab.

Associated data

ClinicalTrials.gov/NCT04001634