CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

HPV Incidence

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study.

Supporting Evidence

A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don't think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

No Evidence for Screening Sexual Partners

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients' partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they've already swapped. Just because they suddenly found that one of them got cancer from it doesn't mean the other one will."

More Research Needed on Vaccines for Prevention

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Second Study: Four Assays Used to Determine HPV Status

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported.

Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

HPV Incidence

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study.

Supporting Evidence

A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don't think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

No Evidence for Screening Sexual Partners

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients' partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they've already swapped. Just because they suddenly found that one of them got cancer from it doesn't mean the other one will."

More Research Needed on Vaccines for Prevention

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Second Study: Four Assays Used to Determine HPV Status

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported.

Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

HPV Incidence

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study.

Supporting Evidence

A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don't think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

No Evidence for Screening Sexual Partners

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients' partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they've already swapped. Just because they suddenly found that one of them got cancer from it doesn't mean the other one will."

More Research Needed on Vaccines for Prevention

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Second Study: Four Assays Used to Determine HPV Status

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported.

Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO – In findings that are likely to change clinical practice, a randomized phase III trial has shown that extending the duration of adjuvant imatinib therapy markedly improves outcomes in patients with resected gastrointestinal stromal tumor who are at high risk for recurrence.

Compared with their counterparts given imatinib (Gleevec) for just 1 year after surgery, patients given the drug for 3 years were 54% less likely to have had a recurrence and 55% less likely to have died at the 5-year mark.

In addition, extended treatment with the drug, an oral agent that inhibits multiple tyrosine kinases, was generally well tolerated.

Lead author Dr. Heikki Joensuu presented the trial’s findings in a press briefing and later in a plenary session at the annual meeting of the American Society of Clinical Oncology.

"These data are pretty compelling," commented Dr. Joensuu, professor of oncology at Helsinki University Central Hospital. "I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future."

At present, there are no data from randomized trials to suggest that taking this therapy out further will yield even greater benefit, Dr. Joensuu said. Instead, he predicted, the strategy going forward will be to stop imatinib at 3 years but closely follow up patients to catch any recurrences early.

"There is evidence that when we restart imatinib, the patients will respond to imatinib again," he explained. "And those patients who have a small tumor volume will have a good chance of responding to imatinib rechallenge for many years, even after 10 years."

Dr. Mark G. Kris, moderator of the press briefing, commented, "I think the entire oncology community was extremely excited when we saw that survival curve and those numbers at 5 years, and I think that’s one of the reasons that this paper was chosen for the plenary session. It’s one of the amazing stories in oncology that ... patients who had a 50% death likelihood at 5 years, by taking four pills [of imatinib] a day, are alive at 5 years, and the vast majority alive are cancer free."

The data will likely be taken into consideration by professional oncology organizations as they update their practice guidelines, according to Dr. Kris, chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "This is the kind of data that does change guidelines, absolutely, and I believe that’s what we are going to see," he said.

Participants in the trial, formally known as the SSGXVIII/AIO trial, were 400 patients in Finland, Germany, Norway, and Sweden who underwent resection of stem cell growth factor (KIT)-positive gastrointestinal stromal tumor (GIST), and were at high risk for recurrence according to modified Consensus Criteria.

In the pre-imatinib era, such patients had at least 50% risks of recurrence and death in the first 5 years after resection, according to Dr. Joensuu.

The patients were assigned in equal numbers to treatment with imatinib 400 mg/day for either 1 year (shown to improve recurrence-free survival in a previous trial) or 3 years on an open-label basis. The drug targets the KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, the genes for which are mutated in most GISTs, as well as the BCR-ABL tyrosine kinase.

Safety results showed that "the treatment was generally well tolerated," Dr. Joensuu reported. The most common adverse events were anemia, periorbital edema, fatigue, nausea, and muscle cramps, all of which were generally mild.

Relative to their counterparts in the 1-year group, patients in the 3-year group were more likely to experience grade 3/4 adverse events (33% vs. 20%) and to stop treatment because of adverse events (14% vs. 8%), however.

Intention-to-treat efficacy results showed that after a 54-month median follow-up, the 5-year rate of recurrence-free survival was significantly better with 3 years of imatinib than with 1 year (65.6% vs. 47.9%; hazard ratio, 0.46; P less than .0001). "Resistance was not a big problem in the current study," Dr. Joensuu noted.

In addition, although the 5-year rate of overall survival was high in both groups, it was likewise superior with 3 years of imatinib (92.0% vs. 81.7%; HR, 0.45; P = .019). The majority of deaths were due to GIST.

There may be other pharmacotherapy options for patients at high risk for GIST recurrence, he acknowledged. "We need to have the next generation of trials, and we also may need to address sequential treatment and combinations. And we need to learn more about the biology of the disease."

Abstract discussant Dr. Charles D. Blanke, chief of medical oncology at the University of British Columbia, Vancouver, said, "If you have a patient who has a high-risk GIST – at least as defined by the study – giving him or her 3 years of imatinib represents the new gold standard. For now, the overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting hoping to ‘catch up’ when a patient has recurrent metastatic disease."

That said, the optimal duration of therapy remains unknown. "There are plenty of reasons to think giving imatinib for a longer period would be better, but that theory remains unproven," he said. "For now, if I were a patient with resected GIST and I had a compliant oncologist, I would request more. As a compliant oncologist, I personally will offer patients treatment to eternity, meaning indefinitely."

However, Dr. Blanke added, "I reserve the right to change my mind pending the longer-term overall survival results of SSGXVIII and the findings in PERSIST-5," a trial assessing 5 years of adjuvant imatinib. "But I don’t think GISTs are curable, even in the adjuvant setting, and I bet I won’t [change my mind]."

Oncologists must also decide for themselves which patients to treat, as the high-risk category used in the SSGXVIII trial included patients with possible recurrence risks ranging from 34% up to nearly 100%.

"But given the possibility that we need to treat for a very long time, coupled with the difficulty patients have taking long-duration drugs, I probably will recommend therapy for those with a 50% chance or greater of recurrence following surgery alone," he said. "I suspect many of you will choose a lower number."

Dr. Joensuu reported being a consultant to and receiving honoraria from Novartis. Novartis provided the drug and partly funded the trial. Dr. Kris reported being a consultant to GlaxoSmithKline, Merck, and Sanofi-Aventis. Dr. Blanke reported being a consultant to Novartis.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.

CHICAGO –More good news on ipilimumab for metastatic melanoma emerged from the results of a trial reported at the annual meeting of the American Society of Clinical Oncology.

In a double-blind, randomized, phase III study, nearly 21% of 250 metastatic melanoma patients who underwent first-line treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) in combination with dacarbazine were alive after 3 years, compared with 12% of 252 patients given placebo and dacarbazine, Dr. Jedd Wolchok reported during a plenary session at the meeting.

Overall survival was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the placebo plus dacarbazine group. The study was simultaneously published in the New England Journal of Medicine (2011 June 5;doi:10.1056/NEJMoa1104621).

A divergence in the survival curve was evident at 1 year, with 47% survival in the ipilimumab plus dacarbazine group, compared with 36% in the placebo plus dacarbazine group; at 2 years, the survival rates were 28% and 18%, respectively. The hazard ratio was 0.72, or 28% reduction in death.

At last year’s ASCO meeting, ipilimumab monotherapy was shown to prolong survival in previously treated metastatic melanoma patients. The drug was approved earlier this year as a first-line monotherapy treatment at a dosage of 3 mg/kg.

This is the first trial to show efficacy and safety of combining immunotherapy and chemotherapy in metastatic melanoma, said Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York. The next step for ipilimumab combination therapy is to look to other combination therapies, such as the investigational agent vemurafenib (PLX4032), as well as other targeted agents and immune-modifying agents.

Dr. Wolchok cautioned that ipilimumab is approved only as a monotherapy and should only be used at the approved dose. Any use in combination therapy should be conducted as part of a clinical trial, several of which are ongoing or about to get underway.

In another plenary presentation at ASCO, Dr. Paul Chapman, also of Memorial Sloan-Kettering, reported a 63% reduction in risk of death with vemurafenib, compared with dacarbazine alone, in metastatic melanoma patients with BRAF mutations. Vemurafenib is an investigational oral drug that inhibits BRAF kinase.

In Dr. Wolchok’s study, progression-free survival was not significantly different between the two treatment groups. Ipilimumab, a monoclonal antibody that blocks CTLA-4 and augments T-cell activation, may improve survival by re-establishing an immuno-equilibrium that allows patients to survive despite the presence of tumors, he said. "The immune system is a ‘living drug,’ able to adapt itself to changes in the tumor ... overall survival is a more accurate way to gauge treatment effectiveness than progression-free survival."

In the trial, patients received either ipilimumab (10 mg/kg, three times per week for 4 weeks) plus dacarbazine (850 mg/m², three times per week for 8 weeks) or placebo plus dacarbazine at the same dose and schedule. More than half of the patients in the study had MC1 disease.

Tumors were assessed at weeks 1, 12, and 24 in the protocol. For the maintenance therapy section of the trial, placebo or ipilimumab at 10 mg/kg once every 12 weeks was given until the disease progressed or patients had toxic effects.

Treatment discontinuations due to disease progression and adverse events were higher in the ipilimumab plus dacarbazine group; 92 patients received all four doses, compared with 165 patients in the placebo plus dacarbazine group.

Most discontinuations were due to disease progression, which occurred in 46% of the ipilimumab plus dacarbazine group and in 77% of the placebo plus dacarbazine group.

Of those who received at least one dose of therapy, 89 of 247 patients in the ipilimumab plus dacarbazine group and 10 of 251 patients given dacarbazine plus placebo discontinued. In the ipilimumab plus dacarbazine group, 85 of 247 discontinued after the induction phase because of a drug-related adverse event as did 10 of 251 in the placebo plus dacarbazine group.

After the maintenance dose, 4 of 43 in the dacarbazine plus ipilimumab group and none of the 53 in the placebo plus dacarbazine group discontinued therapy after receiving the maintenance dose.

The only treatment-related death occurred in the placebo plus dacarbazine group. Immune-related adverse events were seen in 78% of the ipilimumab plus dacarbazine group and in 38% of the placebo plus dacarbazine group. Grade 3 and 4 adverse events occurred in 38% of the ipilimumab plus dacarbazine group and in 4.4% of the placebo plus dacarbazine group. Liver function abnormalities were the most common immune-mediated adverse event. Most of the patients received steroids and their liver function normalized.

The study was funded by Bristol-Myers Squibb, the maker of ipilimumab. Dr. Wolchok is a consultant/advisor to Bristol-Myers Squibb.