Trastuzumab Emtansine: Antibody-drug Conjugate in Treatment of Human Epidermal Growth Factor Receptor-2-Positive Metastatic Breast Cancer

Ajay Gogia; Jagdish Nigade; Chirag Desai; Babu K Govind; Chetan Deshmukh; Binay Swarup

doi:10.4103/ijmpo.ijmpo_53_17

Indian Journal of Medical and Paediatric Oncology, Table of Contents

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2018; 39(01): 79-87
DOI: 10.4103/ijmpo.ijmpo_53_17

Review Article

Trastuzumab Emtansine: Antibody-drug Conjugate in Treatment of Human Epidermal Growth Factor Receptor-2-Positive Metastatic Breast Cancer

Authors

Ajay Gogia

Department of Medical Oncology, Dr. Bhimrao Ramji Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Jagdish Nigade

Roche Products (India) Pvt Ltd. Bandra Kurla Complex, Bandra (E), Mumbai, Maharashtra, India
Chirag Desai

Department of Medical Affairs, Hemato-Oncology Clinic, Vedanta Institute of Medical Sciences, Navrangpura, Ahmedabad, Gujarat, India
Babu K Govind

Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
Chetan Deshmukh

Department of Oncology, Deenanath Mangeshkar Hospital and Research Center, Erandwane, Pune, Maharashtra, India
Binay Swarup

Roche Products () Pvt Ltd. Bandra Kurla Complex, Bandra (E), Mumbai, Maharashtra, India

Abstract

The human epidermal growth factor receptor-2 (HER2)-targeted therapies have improved clinical outcomes for patients at any stage of HER2-positive breast cancer (BC). Trastuzumab, a monoclonal antibody that targets the HER2 receptor on BC cells, showed improved survival in metastatic BC (MBC). However, resistance to therapy arises in the majority of patients with advanced disease. Antibody–drug conjugate (ADC) is a relatively new development to deliver cytotoxic drugs specifically to cancer cells. Trastuzumab emtansine (T-DM1) is a HER2-targeted ADC, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent, emtansine (DM1, derivative of maytansine). T-DM1 has been approved for use in patients with MBC who have failed prior therapy with trastuzumab and a taxane. Dose finding Phase I study established the maximum tolerated dose at 3.6 mg/kg every 3 weeks. Phase I and II studies of T-DM1 have shown clinical activity and a favorable safety profile in HER2-positive MBC patients. The Phase III randomized EMILIA and TR3RESA trials demonstrated that T-DM1 significantly improves progression-free and overall survival in pretreated HER2-positive MBC patients. Nausea and fatigue are most commonly reported adverse drug reactions with T-DM1 and cardiac toxicity comparable with standard of care therapies. The drug is well tolerated in most patients, with a predictable pharmacokinetic profile and minimal systemic exposure to free cytotoxic DM1. T-DM1 has emerged as an effective therapeutic option for the management of patients with HER2-positive MBC.

Keywords

Drug conjugate - human epidermal growth factor receptor-2 - metastatic breast cancer - Trastuzumab emtansine

Full Text

References

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