Rad001 (everolimus)

Overview: TAMRAD Clinical Trial
The Phase II TAMRAD trial conducted by the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens et du sein (GINECO Group, France) was designed to evaluate the efficacy and safety of everolimus in combination with hormonal therapy tamoxifen versus tamoxifen alone for the treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer with prior exposure to aromatase inhibitors (AI)1. Overview
Phase II trial evaluating the efficacy and safety of everolimus in combination with tamoxifen in AI pretreated HR+/HER2- metastatic breast cancer patients compared to tamoxifen therapy alone1 Trial Design
 Randomized trial of 111 patients with HR+/HER2- metastatic breast cancer with prior exposure to AI treatment (in adjuvant and/or metastatic setting)1  Patients randomized 1:1 to receive1: o Everolimus plus tamoxifen (10 mg/day and 20 mg/day respectively; n=54) To evaluate whether there is a clinical benefit, as defined as complete response, Objective
partial response and stable disease (CR+PR+SD) at six months in the everolimus plus tamoxifen arm1 Secondary
To evaluate time to disease progression, overall survival, objective response rate and Objectives
safety of everolimus in combination with tamoxifen1  The study met its primary endpoint, showing that the proportion of metastatic breast cancer patients without tumor progression at six months was 61.1% in the everolimus plus tamoxifen arm (95% confidence interval [CI], 46.9 to 74.1) vs. 42.1% in patients treated with tamoxifen alone (95% CI, 29.1 to 55.9); p=0.045)1  Time to disease progression was delayed by a median of 8.6 months in patients treated with everolimus plus tamoxifen vs. 4.5 months in patients treated with tamoxifen alone, providing a statistically significant reduction in the risk of disease progression by 47% (hazard ratio=0.53 [95% CI, 0.35 to 0.81]; log-rank test: p=0.0026, exploratory analysis)1 Dosing of everolimus had to be decreased for 15 patients (28%). Treatment was stopped due to toxicities in three patients in the everolimus plus tamoxifen arm and in four patients in the tamoxifen-only arm. Grade 3-4 adverse events (>10%) were stomatitis (11% in the combination arm and 0% in the tamoxifen-only arm), pain (9% in the combination arm and 19% in the tamoxifen-only arm) and fatigue (6% in the combination arm and 11% in the tamoxifen-only arm)1.
About everolimus
Afinitor® (everolimus) tablets is approved in more than 70 countries and regions including the United States
and the European Union in the oncology settings of advanced renal cell carcinoma (RCC) following
vascular endothelial growth factor (VEGF)-targeted therapy and advanced progressive neuroendocrine
tumors of pancreatic origin (pNET).
Everolimus is also available from Novartis for use in non-oncology patient populations under the brand
names Votubia®, Certican® and Zortress® and is exclusively licensed to Abbott and sublicensed to Boston
Scientific for use in drug-eluting stents.
Indications vary by country and not all indications are available in every country. Access to everolimus
outside of the approved indications has been carefully controlled and monitored in clinical trials designed to
better understand the potential benefits and risks of the compound. As an investigational compound the
safety and efficacy profile of everolimus has not yet been established outside the approved indications.
Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially
available for additional indications anywhere else in the world.
Important Safety Information about Afinitor (everolimus) tablets
Afinitor can cause serious side effects including lung or breathing problems, infections, and renal failure
which can lead to death. Mouth ulcers and mouth sores are common side effects. Afinitor can affect blood
cell counts, kidney and liver function, and blood sugar and cholesterol levels. Afinitor may cause fetal harm
in pregnant women. Women taking Afinitor should not breast feed.
The most common adverse drug reactions (incidence ≥15%) are mouth ulcers, diarrhea, feeling weak or
tired, skin problems (such as rash or acne), infections, nausea, swelling of extremities or other parts of the
body, loss of appetite, headache, inflammation of lung tissue, abnormal taste, nose bleeds, inflammation of
the lining of the digestive system, weight decreased and vomiting. The most common Grade 3-4 adverse
drug reactions (incidence ≥2%) are mouth ulcers, feeling tired, low white blood cells (a type of blood cell
that fights infection), diarrhea, infections, inflammation of lung tissue, and diabetes. Cases of hepatitis B
reactivation and blood clot in the lung and leg have been reported.
References
1.
Bachelot, T. et. al. TAMRAD: A GINECO Randomized Phase II Trial of Everolimus in Combination With Tamoxifen Versus Tamoxifen Alone in Patients (pts) With Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer (MBC) With Prior Exposure To Aromatase Inhibitors (AI). 33rd San Antonio Breast Cancer Symposium. 2010.

Source: http://www.novartisoncology.com/files/media/research/FINAL%20-%20Global%20Afinitor%20Breast%20-TAMRAD%20Trial%20Fact%20Sheet.pdf