GAITHERSBURG, Md--The FDA's Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend approval of Ciba-Geigy Corp.'s Aredia (pamidronate disodium for injection) for the treatment of osteolytic bone metastases in breast cancer patients undergoing either chemotherapy or hormonal therapy.
The panel recommended approving the drug for hormonal therapy patients despite the concerns of some members that the supporting data appeared weak. The panel declined to recommend that FDA approve Aredia for use in bone metastases from other types of tumors.
Aredia, a bisphosphonate, is a new class of osteoclast inhibitor that retards the resorption of bone. Ciba-Geigy officials and their outside consultants discussed two placebo-controlled, double-blinded, randomized trials in breast cancer patients who had developed lytic bone lesions.
One, P19, involved 382 patients receiving chemotherapy; the second, P18, studied 371 patients receiving hormonal treatments. Both trials used "skeletal related events [SREs] excluding hypercalcemia" as their primary endpoint. These included pathological fractures, spinal cord compression, radiation for pain, and surgery to bone, said John Seaman, PharmD, of Ciba-Geigy.
In P19, women getting Aredia in addition to chemotherapy had a median time to their first SRE of 13 months, compared with 7 months for the women in the chemotherapy-placebo group. The Aredia-treated women also suffered fewer SREs, a mean of 2.1 per year, compared with 3.3 for the placebo group.
Trial P18 showed that women receiving hormonal therapy plus Aredia had a median time to first SRE of 10.9 months, compared with 7.4 months for the placebo group. The Aredia group experienced a mean of 2.4 SREs per year vs an annual mean of 3.5 SREs in the placebo women.
In his efficacy and safety analysis, Dr. Seaman also presented data from P12, an Aredia trial in 392 multiple myeloma patients. Among the P19 and P12 patients, he said, "after 9 to 21 months of monthly therapy, the proportion of patients having SREs was significantly less on Aredia than on placebo."