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Neratinib: an option for HER2-positive metastatic breast cancer

Joyce A O'Shaughnessy^1,2, Ruth O'Regan³, Claudine Isaacs⁴

¹Baylor University Medical Center, Dallas, Texas.

Clinical Advances in Hematology & Oncology : H&O

|April 12, 2021

Abstract:

Metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is currently incurable. The primary goals of treatment are to prolong survival while optimizing quality of life. Several agents are now available in this setting, including neratinib, tucatinib, ado-trastuzumab emtansine, and trastuzumab deruxtecan. Neratinib in combination with capecitabine was recently approved for the treatment of adult patients with advanced or metastatic breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting. Neratinib is an oral pan-HER inhibitor that binds covalently to the kinase site, providing irreversible binding. Phase 3 data showed that the combination of neratinib plus capecitabine improved progression-free survival vs lapatinib plus capecitabine. The duration of response was longer among patients in the neratinib arm. Neratinib plus capecitabine was also active against brain metastases associated with refractory, HER2-positive breast cancer, and this combination is listed in guidelines from the National Comprehensive Cancer Network for this indication. When combined with fulvestrant, neratinib demonstrated efficacy in patients with HER2-positive breast cancer, regardless of their hormone receptor status. Ongoing trials are evaluating the ability of neratinib to treat brain metastases, as well as the efficacy and safety of the triplet combination of neratinib, fulvestrant, and trastuzumab in this setting.

Insights

Neratinib plus capecitabine offers a new treatment option for advanced HER2-positive breast cancer, improving progression-free survival and showing activity against brain metastases.

Area of Science:

Oncology
Pharmacology

Background:

Metastatic HER2-positive breast cancer remains incurable, necessitating novel therapeutic strategies.
Current treatments aim to extend survival and maintain quality of life.
Several anti-HER2 agents are available, including neratinib, tucatinib, ado-trastuzumab emtansine, and trastuzumab deruxtecan.

Purpose of the Study:

To evaluate the efficacy and safety of neratinib in combination with capecitabine for advanced or metastatic HER2-positive breast cancer.
To assess neratinib's activity against brain metastases in refractory HER2-positive breast cancer.
To explore neratinib's efficacy in combination with fulvestrant, irrespective of hormone receptor status.

Main Methods:

Phase 3 clinical trial comparing neratinib plus capecitabine versus lapatinib plus capecitabine.
Evaluation of progression-free survival, duration of response, and activity against brain metastases.
Analysis of neratinib's efficacy when combined with fulvestrant in HER2-positive breast cancer patients.

Main Results:

Neratinib plus capecitabine demonstrated improved progression-free survival compared to lapatinib plus capecitabine.
A longer duration of response was observed in the neratinib arm.
The combination showed activity against brain metastases and is recognized in NCCN guidelines.

Conclusions:

Neratinib plus capecitabine is an approved treatment for patients with advanced or metastatic HER2-positive breast cancer after prior anti-HER2 therapies.
Neratinib offers a valuable therapeutic option, including for patients with brain metastases.
Ongoing research investigates neratinib's role in combination therapies for brain metastases and other settings.

Read full analysis

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