According to the results of a large Phase 3 clinical trial, Zometa increases overall and progression-free survival rates among multiple myeloma patients compared to Bonefos and is more effective in preventing bone loss and fractures.  Additonally, the trial found that inclusion of thalidomide as part of an induction regimen further improved responses. 

Dr. Gareth Morgan of the Royal Marsden Hospital in London presented the results, recently published in The Lancet (abstract), at the American Society of Hematology (ASH) annual meeting in Orlando today.

“I think it is incredibly compelling that the Zometa-treated group has a statistically significantly longer overall survival that amounts to about 5.5 months, which I think is clinically significant,” stated Dr. Morgan.

According to Dr. Morgan, the increase in overall survival observed in Zometa patients are a result of inherent anti-cancer effects of Zometa rather than a decrease in skeletal-related events. He added that an analysis demonstrated that there was no relationship between a reduction in skeletal-related events and patient survival. Additionally, patients without myeloma bone disease experienced a survival benefit when treated with Zometa.

Multiple myeloma is commonly associated with a number of skeletal complications, including fractures, spinal cord compression, elevated calcium levels in the blood, and severe bone pain.

These complications arise as a result of skeletal weakening due to bone lesions. Bone lesions are the result of an under activity or absence of cells responsible for bone formation paired with the over activity of cells that degrade bone (see related Beacon news). Up to 90 percent of multiple myeloma patients may develop bone lesions over the course of their disease.

Zometa (zoledronic acid) and Bonefos (clodronate) are both bisphosphonates, which reduce bone loss and fractures by inhibiting the specialized cells that breakdown bone. Zometa is approved for use in the United States, and Bonefos, while not approved for use in the United States, is currently approved in Canada, the United Kingdom, and Italy.

Previous pre-clinical and clinical trials have indicated that Zometa may have anti-cancer effects, in addition to preventing bone loss and related complications. However, no clinical trials have shown that Zometa has anti-myeloma effects.

Dr. Morgan and his colleagues compared the anti-myeloma effects of Zometa to Bonefos by evaluating the effect of the two drugs on overall survival and progression-free survival in myeloma patients. They also evaluated the drugs’ effects on skeletal-related events.

A total of 1,960 newly diagnosed multiple myeloma patients participated in the study. Each participant received either Zometa or Bonefos following induction therapy. Patients followed intensive or non-intensive pathways, which differed in terms of the induction regimen used and whether or not patients underwent a stem cell transplant.  After bisphosphonate treatment, all patients also had the option of receiving maintenance treatment with thalidomide (Thalomid).

In the intensive treatment group, the patients who received thalidomide (Thalomid) had a statistically significant higher percentage of complete responses and very good partial responses than those who did not. 

Though it was not statistically significant, Dr. Morgan noted that a higher percentage of patients in the intensive treatment group receiving Zometa achieved complete and very good partial responses (36 percent) than those receiving Bonefos (34.7 percent).

In the non-intensive treatment group, however, there was a statistically significant improvement in response rates for patients receiving Zometa compared to those receiving Bonefos.

At a median follow-up of 3.7 years, patients taking Zometa had a 16 percent reduced risk of death compared to those on Bonefos.  Likewise, Zometa improved progression-free survival by 12 percent compared with Bonefos.

Of the patients taking Zometa, 27 percent experienced a skeletal-related event, compared to 35 percent taking Bonefos. The reduction in skeletal-related events was observed regardless of whether or not patients had bone disease when they enrolled in the trial.

Dr. Morgan also noted that for elderly patients in the non-intensive treatment group, the risk of bone disease was further reduced in those patients who received thalidomide as part of their induction therapy. 

Side effects were minimal for both treatments, and there was no difference in kidney function deterioration among the Bonefos and Zometa groups. However, the rate of osteonecrosis of the jaw, a condition that is associated with a loss of blood supply to the jaw resulting in jawbone death, was higher in the Zometa group (4 percent) compared to the Bonefos group (>1 percent).

For more information, please see abstract 311 on the American Society of Hematology annual meeting website and the Novartis press release.