Targeted Therapy Drugs: Trastuzumab

Targeted Therapy Drugs: Trastuzumab-Introduction

Trastuzumab, developed by Genentech, Inc., a monoclonal antibody that interferes with the HER2/neu receptor. It is approved in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil), for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Targeted Therapy Drugs: Trastuzumab-Target

The target of this drug is HER2/neu receptor. The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER protein, Human Epidermal Growth Factor Receptor, binds to Human Epidermal Growth Factor, and stimulates cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.

Targeted Therapy Drugs: Trastuzumab-Efficacy

The approval is based on a significant improvement in median overall survival (OS) of 2.5 months with trastuzumab plus chemotherapy treatment compared to chemotherapy alone demonstrated in a single, international, multicenter, open-label, randomized clinical trial, BO18255 (ToGA trial). A total of 594 patients with locally advanced or metastatic HER2 overexpressing adenocarcinoma of the stomach or GE junction were randomized (1:1) to receive either trastuzumab plus chemotherapy or chemotherapy alone.
The trial was closed after the second interim analysis when 167 deaths had occurred on the trastuzumab arm and 184 deaths on the control arm. In the final OS analysis, the median OS was 13.5 months (95% CI: 11.7, 15.7) and 11.0 months (95% CI: 9.4, 12.5) in the trastuzumab and control arms, respectively. The hazard ratio (HR) was 0.73 [(95% CI: 0.60, 0.91); p-value, two sided = 0.0038 (nominal significance level of 0.0193)] in favor of the trastuzumab arm.

Targeted Therapy Drugs: Trastuzumab-Side Effect

The most common adverse reactions (< 10%) associated with trastuzumab were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common grade 3 and 4 adverse reactions (>5%) related to trastuzumab were neutropenia (35%), anemia (12%), diarrhea (9%), nausea (8%), anorexia (7%), and vomiting (6%). About 37% of patients receiving trastuzumab plus chemotherapy had infusion-related reactions. No grade 4 infusion reactions or deaths related to infusion reactions were reported. Cardiac adverse reactions occurred at the same incidence on both study arms. The incidence of cardiac failure was < 1%. Over 90% of the deaths in both arms were due to disease progression or disease-related complications. The most common adverse reactions resulting in treatment discontinuation in the trastuzumab arm were infection, diarrhea, and febrile neutropenia.

Targeted Therapy
What is Targeted Therapy
Targeted Therapy: Targets
Targeted Therapy for Cancer
EGFR Targeted Therapy
HER2 Targeted Therapy
VEGF Targeted Therapy
BRAF Targeted Therapy
ALK Targeted Therapy
Immune Checkpoint Targeted Therapy
Targeted Therapy Drugs
Targeted Therapy Drugs: Elotuzumab
Targeted Therapy Drugs: Necitumumab
Targeted Therapy Drugs: Daratumumab
Targeted Therapy Drugs: Ramucirumab
Targeted Therapy Drugs: Trastuzumab
Targeted Therapy Drugs: Vemurafenib
Targeted Therapy Drugs: Crizotinib
The Differences between Chemotherapy and Targeted Therapy
Side Effects of Targeted Therapy
Oral Targeted Therapy
Targeted Therapy Resistance
How does Targeted Therapy Work