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Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.

ABSTRACT: PURPOSE:This review aims to present the preclinical and clinical data regarding efficacy and safety of lapatinib alone and in combination with other agents in the treatment of human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer. BACKGROUND:HER2-positive (HER2+) breast cancer remains a treatment challenge. It is more aggressive than other breast cancers and it is associated with a poor outcome. Targeted therapy for HER2+ breast cancer has significantly changed the clinical course of the disease. Despite advances in therapy, there remains an unmet need in the treatment of HER2+ breast cancer. Lapatinib is a novel, orally bioavailable epidermal growth factor receptor/HER2+ targeted agent. Many trials have investigated the efficacy and safety of lapatinib alone and in conjunction with other agents in the treatment of HER2+ breast cancer. METHODS AND RESULTS:Preclinical and clinical trials of lapatinib have shown that it is effective in the treatment on HER2+ breast cancer. More important, studies show that it is effective in the setting of trastuzumab resistance and in the treatment of central nervous system metastases, both of which are current treatment challenges. Furthermore, lapatinib is effective in conjunction with trastuzumab in the treatment of early breast cancer. Data regarding the safety of lapatinib show that it is generally well tolerated; however, multiple studies have shown significant (grade 3 and 4) diarrhea and rash associated with lapatinib, thereby limiting its use. Carditoxicity has not been a significant adverse event associated with the use of lapatinib. CONCLUSION:Lapatinib is effective alone and in conjunction with other agents in the treatment of HER2+ breast cancer. However, its use is limited by significant diarrhea and rash.

SUBMITTER: Hurvitz SA

PROVIDER: S-EPMC3846547 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.

Hurvitz Sara A SA Kakkar Reva R

Breast cancer (Dove Medical Press) 20120403

<h4>Purpose</h4>This review aims to present the preclinical and clinical data regarding efficacy and safety of lapatinib alone and in combination with other agents in the treatment of human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer.<h4>Background</h4>HER2-positive (HER2+) breast cancer remains a treatment challenge. It is more aggressive than other breast cancers and it is associated with a poor outcome. Targeted therapy for HER2+ breast cancer has significantly chan ...[more]

PMID: 24367193

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Project description: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.

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Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.

Publications

Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.

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