FRIMLEY, England, June 5, 2010 /PRNewswire/ --

- Data show zoledronic acid, a bisphosphonate, provided significant clinical anticancer benefit and significantly reduced risk of skeletal- related events(1,2) - Overall survival advantage observed with zoledronic acid plus chemotherapy versus oral clodronate plus chemotherapy is independent of skeletal-related event benefit(1) - Results from a separate five-year follow-up study of hormone receptor-positive premenopausal early breast cancer patients showed significant improvement in progression-free survival with zoledronic acid in this patient population(2)

New data to be presented tomorrow at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, from the Myeloma IX study, show that zoledronic acid plus first-line chemotherapy significantly improved overall survival for newly diagnosed multiple myeloma patients by 16% (P=0.0118) and progression-free survival by 12%, (P=0.0179) compared to oral clodronate plus first-line chemotherapy(1). The 5.5 month survival improvement demonstrated by zoledronic acid in this study of nearly 2,000 UK patients was independent of the drug's effect on bone complications ( also known as skeletal-related events or SREs)(1). Zoledronic acid was significantly superior to oral clodronate in the prevention of bone complications associated with multiple myeloma, reducing the relative risk of SREs 24% more than clodronate (P=0.0004)(1).

Zoledronic acid is licensed in the UK for the prevention of bone complications (skeletal-related events, or SREs) in multiple myeloma and across a broad range of metastatic cancers (breast, prostate, lung and other solid tumours) involving bone, as well as for the treatment of hypocalcaemia of malignancy (HCM)(3).

This is the first time we have seen in a large, phase III independent study that zoledronic acid plus chemotherapy significantly improves survival in patients with myeloma. said Eric Low, Chief Executive of Myeloma UK. This is extremely encouraging news for the 4,000 patients who are diagnosed with myeloma in the UK each year and the results suggest that zoledronic acid has the potential to help myeloma patients live longer.

Other zoledronic acid data presented at ASCO include a five-year follow- up analysis from the Phase III Austrian Breast Colorectal Cancer Study Group 12 (ABCSG-12) trial, which showed that the addition of zoledronic acid to hormonal therapy following surgery improved disease-free survival by 32% (HR=0.68 [95%CI 0.51,0.91], P=0.009) in premenopausal women with hormone receptor-positive (HR+) early breast cancer(2). Data from the ABCSG- 12 study are the basis of the Company's US and European Union regulatory filings for zoledronic acid in the adjuvant treatment of premenopausal hormone receptor-positive early breast cancer.

There is a significant unmet medical need to further reduce the risks of breast cancer recurrence and women are naturally very concerned about the possible return or spread of their disease, said Professor Rob Coleman , Consultant Medical Oncologist at Weston Park Hospital, Sheffield. These five-year data are exciting for oncologists and patients alike because they indicate that adding zoledronic acid to a post-surgical hormonal treatment regimen for premenopausal women with hormone sensitive breast cancer can significantly reduce the risk of recurrence.

Notes to Editors

Myeloma IX Study Details

Myeloma IX is a Phase III, prospective, multicentre, randomised, controlled study to compare intravenous (IV) zoledronic acid (4mg every 3-4 weeks) with oral clodronate (1600 mg daily) in improving survival(4). A total of 1,960 evaluable patients(1) from the United Kingdom with newly diagnosed International Staging System (ISS) stage i, ii or iii multiple myeloma entered either an intensive or non-intensive treatment pathway, determined on the basis of performance status, informed decision and consent4. Patients were randomised for type of bisphosphonate therapy and first-line therapy (induction chemotherapy) on a 1:1 basis(4). Patients in the intensive treatment pathway (younger/more fit patients where intensive high-dose treatment (HDT) with stem cell support was considered appropriate) were randomised to one of four treatment arms to receive either zoledronic acid or oral clodronate in combination with one of two intensive induction chemotherapy regimens(4). Patients in the non-intensive pathway (older/less fit patients where standard dose chemotherapy was considered appropriate) were randomised to one of four treatment arms to receive either zoledronic acid or clodronate in combination with one of two non-intensive induction chemotherapy regimens(4). Following completion of induction and consolidation therapy, patients in both pathways were randomised to thalidomide maintenance or no maintenance therapy, also on a 1:1 basis(4).

The primary study endpoints were overall survival (OS), progression free survival (PFS) and response(4). OS was defined as the length of time after randomisation to death from any cause(4). PFS was defined as the length of time from randomisation to disease progression or death(4). Response was categorised as complete or partial(4). Secondary endpoints included quality of life, SREs (including bone fractures, radiation to bone, surgery to bone and/or spinal cord compression), height loss, toxicity (including thromboembolic events, renal toxicity, hematologic toxicity and graft versus host disease), proportion receiving bortezomib-dexamethasone as early rescue on induction chemotherapy and proportion receiving bortezomib- dexamethasone at relapse(4).

At a median follow-up of 3.7 years, risk of death was reduced by 16% (P=0.0118) and the risk of progression-free survival events fell by 12% (P=0.0179) with zoledronic acid versus oral clodronate(1). The proportion of patients who experienced a SRE was reduced by 24% in those receiving zoledronic acid versus clodronate (27.0% versus 35.3%; P=0.0004)(1). The survival advantage demonstrated by zoledronic acid was observed in patients with stage i, ii, iii newly diagnosed multiple myeloma. This survival advantage was also observed in addition to and independent of the drug's effect on bone complications(1).

The tolerability profile of zoledronic acid is well-established and results from this study were found to be consistent with the known profile. The incidence of osteonecrosis of the jaw (ONJ) in the zoledronic acid and clodronate treatment arms was 3.5% and 0.3%, respectively(1). Renal deterioration was reported to be similar between treatment groups(1).

ABCSG-12 Study Details

ABCSG-12 is an open-label, multicentre, Phase III study that enrolled 1,803 premenopausal women with hormone receptor-positive Stage I or II breast cancer, with fewer than 10 axillary lymph nodes involved(2,5). Patients were recruited for the study after curative surgery and initiation of goserelin treatment for ovarian suppression, and randomly assigned into one of four study groups: (1) anastrozole plus zoledronic acid; (2) anastrozole alone; (3) tamoxifen plus zoledronic acid; (4) tamoxifen alone. Zoledronic acid was administered at a dose of 4mg every six months for a total treatment period of three years and the median follow-up period was 62 months(2,5).

The primary endpoint for all four study arms was disease-free survival(5) . Recurrence-free survival, overall survival and bone-mineral density were secondary endpoints(5). Disease-free survival was defined as the length of time after randomisation during which patients had no local recurrence, contralateral breast cancer, distant metastasis, secondary carcinoma and/or death from any cause(5). Recurrence-free survival was defined as the length of time after randomisation during which patients had no local recurrence, contralateral breast cancer, distant metastasis and/or secondary carcinoma. Bone-mineral density was a primary endpoint of the sub-study(5). Exploratory endpoints included bone metastasis-free survival(5).

At the median follow-up of 62 months, disease-free survival events were reduced by 32% (P=0.009) with zoledronic acid added to hormone therapy versus hormone therapy alone(2). In addition, a positive trend was seen in overall survival with a 34% reduction in the risk of death but this was not statistically significant (P=0.10)(2). This updated analysis continues to show no difference between tamoxifen and anastrozole use, but adding zoledronic acid significantly improves disease-free survival (HR=0.68 for both arms)(2). Overall, side effects were consistent with known drug profiles(5). There were no cases of renal failure or confirmed cases of ONJ in the study(2).

ABOUT ZOMETA (Zoledronic Acid)(3)

Zoledronic acid is indicated for the prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypocalcaemia) in patients with advanced malignancies involving bone. An intravenous bisphosphonate, zoledronic acid is the only licensed bisphosponate to demonstrate efficacy in reducing or delaying bone complications across a broad range of tumour types such as breast, prostate, lung and renal cell cancers, in patients with metastatic disease when administered monthly. Zometa is administered as a 4mg infusion over at least 15 minutes.

Zoledronic acid is indicated for the prevention of skeletal-related events (SREs) in patients with advanced malignancies involving bone across a broad range of tumours. Laboratory research has suggested that zoledronic acid may also help protect patients from the spread of cancer to other parts of the body (distant metastatic sites) and help keep patients recurrence-free.


Zoledronic acid has been associated with reports of renal insufficiency . Patients should be adequately rehydrated and have their serum creatinine assessed prior to receiving each dose of zoledronic acid. Due to the risk of clinically significant deterioration in renal function, single doses of zoledronic acid should not exceed 4 mg and the duration of infusion should be no less than 15 minutes in 100 ml of dilutent. Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates including zoledronic acid. Caution is advised when zoledronic acid is used in aspirin-sensitive patients, or with aminoglycosides, loop diuretics and other potentially nephrotoxic drugs. Zoledronic acid is the same active ingredient as found in Aclasta. Patients being treated with Zometa should not be treated with Aclasta concomitantly.

In clinical trials, the most commonly reported adverse events included flu-like syndrome (fever, arthralgias, myalgias, and skeletal pain), fatigue, gastrointestinal reactions, anaemia, weakness, cough, dyspnoea and oedema. Zoledronic acid should not be used during pregnancy. Zoledronic acid is contraindicated in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of zoledronic acid.

Osteonecrosis of the Jaw (ONJ): ONJ has been reported in patients with cancer receiving treatment including bisphosphonates, chemotherapy, and/or corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors. While on treatment, these patients should avoid invasive dental procedures if possible. Little data are available to suggest whether discontinuation of bisphosphonate therapy reduces the risk of ONJ in patients requiring dental procedures.

For further information please see the summary of product characteristics.

About Novartis

Novartis AG 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, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group's continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in RD activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 98,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit


1. Morgan, GJ, et al. Evaluating the effects of zoledronic acid (ZOL) on overall survival (OS) in patients (Pts) with multiple myeloma (MM): Results of the Medical Research Council (MRC) Myeloma IX study. 2010 ASCO Annual Meeting, abstract 8021.

2. Gnant, M, et al. Mature results from ABCSG-12: Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with endocrine-responsibe early breast cancer. 2010 ASCO Annual Meeting, abstract 533.

3. Zometa. Summary of Product Characteristics.

4. Medical Research Council. Myeloma IX: Myelomatosis therapy trial for patients of all age groups. Version 3.0. 14 March 2006.

5. Gnant, M, et al. Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer. N Engl J Med 2009; 360(7): 679-91.

SOURCE: Novartis

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