Zometa reduces bone loss in patients receiving breast cancer treatment

May 16 2005

Data presented at the American Society of Clinical Oncology (ASCO) annual meeting in Orlando, Florida, demonstrate that Zometa (zoledronic acid), an intravenous bisphosphonate, was shown to inhibit bone loss in postmenopausal women treated with Femara (letrozole) in the adjuvant breast cancer setting (directly following surgery to prevent cancer recurrence).

Importantly, several studies have shown that women treated with hormonal therapy in the adjuvant breast cancer setting are at risk of bone loss. This new data from the Z-FAST (Zometa-Femara Adjuvant Synergy Trial) study offers evidence that Zometa may prevent bone loss in these patients. The final data demonstrate a significant increase in bone mineral density (BMD) after 12 months for those breast cancer patients treated with Femara and upfront Zometa, compared with those who received Femara and delayed Zometa (when the BMD T score falls below -2 or a bone complication occurs).

"These are valuable and encouraging data for the medical community and breast cancer patients," said Rob Coleman, Professor of Medical Oncology at The University of Sheffield. "Zometa is the only bisphosphonate that has demonstrated efficacy in treating bone complications across a broad range of tumor types in metastatic patients, and it is exciting that it has also shown activity against bone loss in breast cancer patients receiving adjuvant treatment with aromatase inhibitors."

The Z-FAST study showed that at the 12-month follow-up, the group of patients receiving upfront Zometa had a mean increase of lumbar spine BMD of 1.9% vs a decrease of 2.4% in the group of patients who received delayed Zometa (p<0.0001). This represents a 4% relative difference in lumbar spine BMD in favour of the upfront Zometa group. Total hip BMD was also higher in the upfront group. Significantly, 8% of patients in the delayed group had decreases in BMD at the 12-month follow-up, which required initiation of Zometa.

"We are committed to developing innovative new treatments for patients with cancer," said John Ketchum, Head of the Oncology Business Unit, Novartis Pharmaceuticals UK. "We are pleased that these data suggest that Zometa may offer patients undergoing adjuvant hormonal therapy for breast cancer and their physicians an important new option."

The Z-FAST study is part of a wider clinical program that includes the international sister trial Zo-FAST. Zo-FAST, which will include more than 900 patients in 30 countries outside the US, including the UK, is investigating the same primary and secondary endpoints and will add to this body of clinical evidence.

The landmark study, Z-FAST, is a multicentre trial designed to help address two important and previously unanswered clinical questions facing the breast cancer community: 1) Does adjuvant treatment of breast cancer with an aromatase inhibitor cause bone loss? 2) Can potential bone loss be prevented by including an IV bisphosphonate in the treatment paradigm?

This open-label, randomised, multicentre trial enrolled 602 postmenopausal women with stage I, II, IIIa, oestrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer who have undergone complete tumour resection, and have no clinical or radiological evidence of recurrent or metastatic disease.

Patients will remain in the study and be treated for a maximum of five years, or until disease progression, with Femara as their adjuvant therapy beginning day one. Patients were randomised to one of two Zometa treatment arms, receiving either an upfront 4 mg, 15-minute infusion of Zometa every six months beginning on day one, or a delayed start 4 mg, 15-minute infusion of Zometa every six months. The delayed start group received Zometa when researchers detected a post-baseline bone mineral density T score below -2.0 SD (standard deviation) or after a bone complication has occurred. Patients will be followed for bone complications including fractures and spinal cord compressions.

Zometa is the first (IV) bisphosphonate to demonstrate efficacy in treating bone complications across a broad range of tumor types such as breast cancer, prostate cancer, renal cell and lung cancers, as well as multiple myeloma. Zometa received its first UK licence in April 2001 for the treatment of tumour-induced hypercalcaemia (TIH). Zometa then received a licence for the prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, TIH) in patients with advanced malignancies involving bone in September 2002. Zometa is most commonly used to treat bone metastases in prostate cancer, breast cancer, lung cancer, multiple myeloma and other solid tumours.