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SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial of over 9,000 women.
The drug was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia. But some findings in the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial have ended that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.
The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene cut the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70%.
It also reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in the subjects, who were aged 60-85 at enrollment. But it did not significantly reduce nonvertebral fractures.
“We need a SERM [selective estrogen-receptor modulator] that would reduce vertebral and nonvertebral fractures,” said Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London. Arzoxifene also linked to increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than placebo.
“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place,” he said.
The researchers are puzzling over how the earlier studies could have been so misleading. Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for reducing invasive breast cancer risk in those at high risk for the cancer or who have osteoporosis. In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than raloxifene. It also resulted in increased bone density at nonvertebral sites and in the spine.
Disclosures: Eli Lilly & Co. funded the trial. Dr. Powles said he has no relevant financial relationships.
'We need a SERM that would reduce vertebral and nonvertebral fractures.'
Source DR. POWLES
SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial of over 9,000 women.
The drug was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia. But some findings in the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial have ended that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.
The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene cut the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70%.
It also reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in the subjects, who were aged 60-85 at enrollment. But it did not significantly reduce nonvertebral fractures.
“We need a SERM [selective estrogen-receptor modulator] that would reduce vertebral and nonvertebral fractures,” said Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London. Arzoxifene also linked to increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than placebo.
“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place,” he said.
The researchers are puzzling over how the earlier studies could have been so misleading. Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for reducing invasive breast cancer risk in those at high risk for the cancer or who have osteoporosis. In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than raloxifene. It also resulted in increased bone density at nonvertebral sites and in the spine.
Disclosures: Eli Lilly & Co. funded the trial. Dr. Powles said he has no relevant financial relationships.
'We need a SERM that would reduce vertebral and nonvertebral fractures.'
Source DR. POWLES
SAN ANTONIO — Arzoxifene, a once-promising selective estrogen-receptor modulator, experienced a fatal meltdown in a phase III trial of over 9,000 women.
The drug was being developed for prevention of both fractures and breast cancer in postmenopausal women with osteoporosis or osteopenia. But some findings in the 9,354-patient randomized, double-blind, placebo-controlled, multinational GENERATIONS trial have ended that, Dr. Trevor Powles said at the San Antonio Breast Cancer Symposium.
The breast cancer prevention portion of GENERATIONS went well: After 48 months of follow-up, arzoxifene cut the incidence of invasive breast cancer by 56%, compared with placebo, and reduced estrogen-receptor–positive invasive breast cancer by 70%.
It also reduced the incidence of vertebral fractures by 41% after 36 months of follow-up in the subjects, who were aged 60-85 at enrollment. But it did not significantly reduce nonvertebral fractures.
“We need a SERM [selective estrogen-receptor modulator] that would reduce vertebral and nonvertebral fractures,” said Dr. Powles, a medical oncologist who is professor emeritus at the Institute of Cancer Research, London. Arzoxifene also linked to increased rates of venous thromboembolism, endometrial polyps, leg cramps, hot flashes, and cholelithiasis, while offering no better protection against cardiovascular events than placebo.
“The overall benefit/risk profile of arzoxifene does not represent a meaningful advancement in the treatment of osteoporosis, so further development of this drug will not take place,” he said.
The researchers are puzzling over how the earlier studies could have been so misleading. Arzoxifene is a benzothiophene SERM, like raloxifene, which is approved in postmenopausal women for the treatment and prevention of osteoporosis as well as for reducing invasive breast cancer risk in those at high risk for the cancer or who have osteoporosis. In early clinical studies, arzoxifene had greater effects on bone mineral density and bone turnover markers than raloxifene. It also resulted in increased bone density at nonvertebral sites and in the spine.
Disclosures: Eli Lilly & Co. funded the trial. Dr. Powles said he has no relevant financial relationships.
'We need a SERM that would reduce vertebral and nonvertebral fractures.'
Source DR. POWLES