Novartis drug Afinitor® met primary endpoint of Phase III study in women with advanced breast cancer; potential to address significant unmet need

Top Quote Novartis announced today that an interim analysis of a pivotal Phase III study showed Afinitor® (everolimus) tablets in combination with exemestane significantly extended progression-free survival (PFS), or time without tumor growth, when compared to placebo plus exemestane in women with advanced breast cancer. End Quote
  • (1888PressRelease) July 06, 2011 - The trial was stopped early after interim results showed the primary endpoint of PFS was met. The study included postmenopausal women with ER+HER2- metastatic breast cancer whose disease has progressed, despite initial endocrine therapy.

    # Trial stopped early after positive interim results showed everolimus plus exemestane extended time without tumor growth
    # Postmenopausal ER+HER2- metastatic breast cancer patients whose disease has progressed despite initial endocrine therapy need effective new treatments[1]
    # Full study results to be submitted for presentation at an upcoming medical congress and worldwide regulatory filings are planned by the end of 2011

    "Despite clinical progress in advanced breast cancer, most women are either initially resistant or develop resistance to endocrine therapy over time. As a result, there is a significant need for new treatment options," said Hervé Hoppenot, President, Novartis Oncology. "Based on these study results, this combination has the potential to extend the time until chemotherapy is needed for these patients."

    The study, BOLERO-2 (Breast cancer trials of OraL EveROlimus-2), is a Phase III, randomized, double-blind, placebo-controlled study of everolimus in combination with exemestane versus placebo plus exemestane in postmenopausal women with estrogen receptor-positive locally-advanced or metastatic breast cancer, whose disease has progressed, despite treatment with the nonsteroidal aromatase inhibitors letrozole or anastrozole[2].

    Results will be presented at an upcoming medical conference and worldwide regulatory submissions are being planned by the end of 2011.

    Everolimus targets mTOR in cancer cells, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. Everolimus is also being investigated for the treatment of patients with HER2+ advanced breast cancer[3].

    Study design
    BOLERO-2 involved more than 700 patients at over 195 sites worldwide[2,4]. Patients in the trial were randomized (2:1) to receive continuous therapy with everolimus 10 mg/day orally or placebo plus oral exemestane 25 mg/day. Patients who had received more than one prior chemotherapy regimen for advanced breast cancer were excluded from enrollment. The primary endpoint was progression free survival. Secondary endpoints included overall survival, overall response rate, incidence of adverse events, patient reported outcomes and clinical benefit rate[2].

    About everolimus
    Afinitor® (everolimus) tablets is approved in the European Union (EU) for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy and also in the US and in Switzerland for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

    In Switzerland, everolimus is approved with the trade name Votubia® (everolimus) tablets for the treatment of patients three years of age and older with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) for whom surgery is not a suitable option. Should everolimus be approved in the EU, the trade name will be Votubia. In the US, Afinitor is approved to treat patients with SEGA associated with TS who require therapeutic intervention but are not candidates for curative surgical resection. The effectiveness of everolimus is based on an analysis of change in SEGA volume. Clinical benefit such as improvement in disease-related symptoms or increase in overall survival has not been shown.

    Afinitor is also approved in the US for the treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The US Food and Drug Administration determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumors have not been established. Novartis has submitted a marketing application for everolimus to the European Medicines Agency for this use, and similar regulatory submissions are under way worldwide.

    In the EU, everolimus is available in different dosage strengths for the non-oncology patient population under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. In the US, everolimus is available in different dosage strengths under the trade name Zortress® for the prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant.

    Everolimus is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

    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. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for breast cancer anywhere in the world. The efficacy and safety of everolimus in breast cancer has not been established.

    Important Safety Information about Afinitor
    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 have been reported.

    The foregoing release contains forward-looking statements that can be identified by terminology such as "to be submitted," "planned," "will," "potential," or similar expressions, or by express or implied discussions regarding potential submissions or approvals for new indications or labeling for Afinitor, or regarding the potential timing of any such submissions or approvals, or regarding potential future revenues from Afinitor. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Afinitor to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Afinitor will be submitted or approved for any additional indications or labeling in any market. Nor can there be any guarantee that Afinitor will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Afinitor could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry and general public pricing pressures; competition in general; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

    About Novartis
    Novartis provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, consumer health products, preventive vaccines and diagnostic tools. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 119,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit

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