Subject: Nerlynx SGM 2178-A P2026

Drug

NERLYNX  (neratinib)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-approved Indications¹

·        Nerlynx is indicated as a single agent for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer, to follow adjuvant trastuzumab based therapy.

·        Nerlynx is indicated in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.

Compendial Uses³

·        Breast Cancer

·        Cervical Cancer

All other indications are considered experimental/investigational and not medically necessary.

Documentation

Submission of the following information is necessary to initiate the prior authorization review, where applicable:

·        Human epidermal growth factor receptor 2 (HER2) status

·        HER2 activating mutation status

Coverage Criteria

Breast cancer^1-3

Authorization of up to 12 months total may be granted for treatment of HER2-positive breast cancer when the requested medication will be initiated after completing adjuvant trastuzumab based therapy when used as a single agent.

Authorization of 12 months may be granted for treatment of HER2-positive breast cancer when either of the following criteria are met:

·        The requested medication is used in combination with capecitabine for members with no response to preoperative systemic therapy or disease that is recurrent unresectable or metastatic, as fourth line or later therapy.

·        The requested medication is used in combination with ado-trastuzumab emtansine or capecitabine for brain metastases.

Authorization of 12 months may be granted for treatment of metastatic breast cancer with HER2 activating mutations when used in combination with fulvestrant and trastuzumab for third-line or later therapy when either of the following criteria are met:

§  The disease is hormone receptor positive and HER2-negative and the member previously received a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor [e.g., Ibrance (palbociclib), Kisqali (ribociclib), Verzenio (abemaciclib)].

§  The disease is triple negative.

Cervical Cancer³

Authorization of 12 months may be granted for subsequent treatment of recurrent or metastatic HER2-mutant cervical cancer when used as a single agent.

Continuation of Therapy

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for an indication listed in the coverage criteria section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen. Adjuvant treatment of breast cancer will be approved for a total of 12 months of therapy.

Place of Service:

Outpatient

The above policy is based on the following references:

1.      Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.; March 2022.

2.     Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016; 17(3):367-77.

3.     The NCCN Drugs & Biologics Compendium® © 2025 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed October 31, 2025.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

July 14, 2026