Jane Salodof MacNeil

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Women taking zoledronic acid monthly for metastatic breast cancer that has spread to the bone may be able to get by with quarterly injections after a year of standard treatment.

The first phase III trial to compare the two dosing schedules for the bisphosphonate found that less frequent therapy produced "noninferior" outcomes compared with the current standard of care, Dr. Carla Ripamonti reported at the annual meeting of the American Society of Clinical Oncology.

Zoledronic acid (Zometa) has been shown to reduce skeletal-related events for up to 2 years in such patients, and international guidelines recommend its use until they experience a substantial decrease in performance status, said Dr. Ripamonti of the National Cancer Institute in Milan, Italy. The thinking behind the current trial was that after a year of treatment, a more convenient regimen "might contribute to improved patient compliance and safety, and help reduce cost while maintaining the efficacy of the drug."

Underscoring the universality of the issue, the invited discussant, Dr. Thomas J. Smith, director of palliative medicine at Johns Hopkins University’s Sidney Kimmel Cancer Center in Baltimore, introduced his comments with the observation, "I’m a breast cancer doctor, and so I see so many people who ask, ‘Do I have to come in every month for my zoledronic acid?’ And the answer is, ‘I don’t know.’ "

Dr. Ripamonti and her coinvestigators randomized 209 women to 4 mg of zoledronic acid every 12 weeks and 216 women to 4 mg every 4 weeks in the 12-month, open-label, multicenter ZOOM trial. All participants had received 9-12 infusions prior to entering the prospective study.

At the trial’s end, 149 and 142 women, respectively, had completed treatment with no difference in the skeletal morbidity rate, the primary end point, in an intent-to-treat analysis. The mean of the ratio of skeletal events per year to time on trial was 0.26 with quarterly treatment and 0.22 with monthly dosing, she reported.

The proportion of patients with skeletal-related events, a secondary end point, also was similar at 14.8% in the quarterly group and 15.3% in the monthly group.

Both schedules were well tolerated, with little difference in adverse events, she reported. The rate of renal side effects was 4% in each arm; osteonecrosis of the jaw occurred in 4 patients on the quarterly schedule and 3 treated monthly.

An assessment of median NTx (N-telopeptides of type I collagen) levels at baseline and every 3 months on study raised some concern, in that the bone resorption marker was increased at 6 months and stayed elevated in the quarterly group, but it did not rise with standard care. This suggests that "caution is needed and longer follow-up is needed to assess whether zoledronic acid every 3 months can maintain adequate efficacy in skeletal-related events over time," said Dr. Ripamonti.

Despite the generally positive results, she noted that the trial was conducted in just one country as an open-label study, it did not have a prespecified imaging frequency, and patients were followed for only 1 year. She urged clinicians to wait for data from the double-blind, phase III Optimize-2 trial, which compared the same dose schedules. Results will be available in the next year, and then oncologists "can decide how to change our clinical practice," she said.

Dr. Smith agreed. It’s "too early" to use NTx levels, he said, recommending that clinicians wait for new data and guidelines. If quarterly dosing becomes possible, he predicted the "cost will be one-third of what it was before."

"So don’t change your current approach, but stay tuned," he told attendees.

Dr. Ripamonti said she had no relevant disclosures. Dr. Smith said he received research funds from the American Cancer Society.

CHICAGO – Women taking zoledronic acid monthly for metastatic breast cancer that has spread to the bone may be able to get by with quarterly injections after a year of standard treatment.

The first phase III trial to compare the two dosing schedules for the bisphosphonate found that less frequent therapy produced "noninferior" outcomes compared with the current standard of care, Dr. Carla Ripamonti reported at the annual meeting of the American Society of Clinical Oncology.

Zoledronic acid (Zometa) has been shown to reduce skeletal-related events for up to 2 years in such patients, and international guidelines recommend its use until they experience a substantial decrease in performance status, said Dr. Ripamonti of the National Cancer Institute in Milan, Italy. The thinking behind the current trial was that after a year of treatment, a more convenient regimen "might contribute to improved patient compliance and safety, and help reduce cost while maintaining the efficacy of the drug."

Underscoring the universality of the issue, the invited discussant, Dr. Thomas J. Smith, director of palliative medicine at Johns Hopkins University’s Sidney Kimmel Cancer Center in Baltimore, introduced his comments with the observation, "I’m a breast cancer doctor, and so I see so many people who ask, ‘Do I have to come in every month for my zoledronic acid?’ And the answer is, ‘I don’t know.’ "

Dr. Ripamonti and her coinvestigators randomized 209 women to 4 mg of zoledronic acid every 12 weeks and 216 women to 4 mg every 4 weeks in the 12-month, open-label, multicenter ZOOM trial. All participants had received 9-12 infusions prior to entering the prospective study.

At the trial’s end, 149 and 142 women, respectively, had completed treatment with no difference in the skeletal morbidity rate, the primary end point, in an intent-to-treat analysis. The mean of the ratio of skeletal events per year to time on trial was 0.26 with quarterly treatment and 0.22 with monthly dosing, she reported.

The proportion of patients with skeletal-related events, a secondary end point, also was similar at 14.8% in the quarterly group and 15.3% in the monthly group.

Both schedules were well tolerated, with little difference in adverse events, she reported. The rate of renal side effects was 4% in each arm; osteonecrosis of the jaw occurred in 4 patients on the quarterly schedule and 3 treated monthly.

An assessment of median NTx (N-telopeptides of type I collagen) levels at baseline and every 3 months on study raised some concern, in that the bone resorption marker was increased at 6 months and stayed elevated in the quarterly group, but it did not rise with standard care. This suggests that "caution is needed and longer follow-up is needed to assess whether zoledronic acid every 3 months can maintain adequate efficacy in skeletal-related events over time," said Dr. Ripamonti.

Despite the generally positive results, she noted that the trial was conducted in just one country as an open-label study, it did not have a prespecified imaging frequency, and patients were followed for only 1 year. She urged clinicians to wait for data from the double-blind, phase III Optimize-2 trial, which compared the same dose schedules. Results will be available in the next year, and then oncologists "can decide how to change our clinical practice," she said.

Dr. Smith agreed. It’s "too early" to use NTx levels, he said, recommending that clinicians wait for new data and guidelines. If quarterly dosing becomes possible, he predicted the "cost will be one-third of what it was before."

"So don’t change your current approach, but stay tuned," he told attendees.

Dr. Ripamonti said she had no relevant disclosures. Dr. Smith said he received research funds from the American Cancer Society.

CHICAGO – Women taking zoledronic acid monthly for metastatic breast cancer that has spread to the bone may be able to get by with quarterly injections after a year of standard treatment.

The first phase III trial to compare the two dosing schedules for the bisphosphonate found that less frequent therapy produced "noninferior" outcomes compared with the current standard of care, Dr. Carla Ripamonti reported at the annual meeting of the American Society of Clinical Oncology.

Zoledronic acid (Zometa) has been shown to reduce skeletal-related events for up to 2 years in such patients, and international guidelines recommend its use until they experience a substantial decrease in performance status, said Dr. Ripamonti of the National Cancer Institute in Milan, Italy. The thinking behind the current trial was that after a year of treatment, a more convenient regimen "might contribute to improved patient compliance and safety, and help reduce cost while maintaining the efficacy of the drug."

Underscoring the universality of the issue, the invited discussant, Dr. Thomas J. Smith, director of palliative medicine at Johns Hopkins University’s Sidney Kimmel Cancer Center in Baltimore, introduced his comments with the observation, "I’m a breast cancer doctor, and so I see so many people who ask, ‘Do I have to come in every month for my zoledronic acid?’ And the answer is, ‘I don’t know.’ "

Dr. Ripamonti and her coinvestigators randomized 209 women to 4 mg of zoledronic acid every 12 weeks and 216 women to 4 mg every 4 weeks in the 12-month, open-label, multicenter ZOOM trial. All participants had received 9-12 infusions prior to entering the prospective study.

At the trial’s end, 149 and 142 women, respectively, had completed treatment with no difference in the skeletal morbidity rate, the primary end point, in an intent-to-treat analysis. The mean of the ratio of skeletal events per year to time on trial was 0.26 with quarterly treatment and 0.22 with monthly dosing, she reported.

The proportion of patients with skeletal-related events, a secondary end point, also was similar at 14.8% in the quarterly group and 15.3% in the monthly group.

Both schedules were well tolerated, with little difference in adverse events, she reported. The rate of renal side effects was 4% in each arm; osteonecrosis of the jaw occurred in 4 patients on the quarterly schedule and 3 treated monthly.

An assessment of median NTx (N-telopeptides of type I collagen) levels at baseline and every 3 months on study raised some concern, in that the bone resorption marker was increased at 6 months and stayed elevated in the quarterly group, but it did not rise with standard care. This suggests that "caution is needed and longer follow-up is needed to assess whether zoledronic acid every 3 months can maintain adequate efficacy in skeletal-related events over time," said Dr. Ripamonti.

Despite the generally positive results, she noted that the trial was conducted in just one country as an open-label study, it did not have a prespecified imaging frequency, and patients were followed for only 1 year. She urged clinicians to wait for data from the double-blind, phase III Optimize-2 trial, which compared the same dose schedules. Results will be available in the next year, and then oncologists "can decide how to change our clinical practice," she said.

Dr. Smith agreed. It’s "too early" to use NTx levels, he said, recommending that clinicians wait for new data and guidelines. If quarterly dosing becomes possible, he predicted the "cost will be one-third of what it was before."

"So don’t change your current approach, but stay tuned," he told attendees.

Dr. Ripamonti said she had no relevant disclosures. Dr. Smith said he received research funds from the American Cancer Society.

CHICAGO – Breast cancer risk is much higher than previously recognized among women who received chest radiation for Hodgkin’s lymphoma when they were children, investigators reported.

By the time these survivors are 50 years of age, breast cancer incidence is 30% – "remarkably similar" to the 31% incidence observed in the high-risk group of women with BRCA1 mutations, Chaya S. Moskowitz, Ph.D., and her colleagues determined in a study presented at the annual meeting of the American Society of Clinical Oncology.

Although the effect was less dramatic, cumulative risk also was elevated in survivors of other childhood cancers treated with chest radiation, reaching 24% overall by age 50, Dr. Moskowitz said at a press briefing. Among the general population of women in the United States, it is 4% at that benchmark, she noted.

Particularly concerning is the heightened risk observed in women who received less radiation than the current threshold at which the Children’s Oncology Group (COG) recommends breast cancer surveillance. The COG says that survivors who received 20 Gy or more of chest radiation should start annual mammograms at age 25 years or 8 years after radiotherapy, whichever comes later.

In this group, 12% of survivors will develop breast cancer by age 40, said Dr. Moskowitz, a biostatistician at Memorial Sloan-Kettering Cancer Center in New York. The study showed that breast cancer incidence also was elevated, albeit not as dramatically – 7% by age 40 – among survivors who received 10-19 Gy of radiation.

Excess risk in those treated with 10-19 Gy warrants "consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with [more than] 20 Gy," the investigators concluded.

About 50,000 survivors received 20 Gy or more of radiation and, therefore, meet the current threshold, Dr. Moskowitz said. Lowering the threshold to include survivors who were treated with 10-19 Gy of chest radiation would add another 7,000-9,000 women.

Increasing public awareness is crucial to increasing surveillance. "Many women who were treated with chest radiation don’t know they have an increased risk of breast cancer," she said. "Their physicians may or may not know, but many physicians are not aware of the guidelines."

Moreover, many survivors don’t know their radiation exposure, and she urged them to try to find those records from long, long ago.

The analysis – a report from the Childhood Cancer Survivor Study (CCSS) and the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study – mined data on 1,268 women survivors of childhood cancers diagnosed from 1970 to 1986 and on 4,570 first-degree relatives of women who had survived at least 1 year after being diagnosed with breast cancer.

Median follow-up was 26 years in the childhood survivors, of whom 175 women were diagnosed with breast cancer as adults. Median latency was 23 years after treatment, and diagnosis was made at a median age of 38 years.

Multiple studies have shown an increased risk of breast cancer in women who received chest radiation as children, Dr. Moskowitz said. This large study has substantially longer follow-up and was surprising in the magnitude of risk it documents.

Chest radiation doses are lower today, and mantle field radiation – which had been used almost exclusively in Hodgkin’s lymphoma – is no longer used, but other regimens are still in the clinic, she added.

Another surprise from the study was that whole lung radiation, even at low doses, can heighten breast cancer risk. "Women treated with whole lung radiation have a risk of breast cancer that is higher than previous recognized and may benefit from surveillance strategies," she said.

"These are striking data and certainly warrant our careful attention," commented press briefing chair Dr. Nicholas Vogelzang, chair and medical director of the developmental therapeutics committee at the Comprehensive Cancer Centers of Nevada, Las Vegas, and cochair of the genitourinary committee for U.S. Oncology Research.

"The benefit of curing a cancer is you can live 25 or more years," he said, noting that curves for breast cancer incidence rose after 25 years in a graphic representation of the data presented. "We have an obligation to those many thousands of young women whom we treated many years ago."

The investigators said that they had no relevant financial disclosures.

CHICAGO – Breast cancer risk is much higher than previously recognized among women who received chest radiation for Hodgkin’s lymphoma when they were children, investigators reported.

By the time these survivors are 50 years of age, breast cancer incidence is 30% – "remarkably similar" to the 31% incidence observed in the high-risk group of women with BRCA1 mutations, Chaya S. Moskowitz, Ph.D., and her colleagues determined in a study presented at the annual meeting of the American Society of Clinical Oncology.

Although the effect was less dramatic, cumulative risk also was elevated in survivors of other childhood cancers treated with chest radiation, reaching 24% overall by age 50, Dr. Moskowitz said at a press briefing. Among the general population of women in the United States, it is 4% at that benchmark, she noted.

Particularly concerning is the heightened risk observed in women who received less radiation than the current threshold at which the Children’s Oncology Group (COG) recommends breast cancer surveillance. The COG says that survivors who received 20 Gy or more of chest radiation should start annual mammograms at age 25 years or 8 years after radiotherapy, whichever comes later.

In this group, 12% of survivors will develop breast cancer by age 40, said Dr. Moskowitz, a biostatistician at Memorial Sloan-Kettering Cancer Center in New York. The study showed that breast cancer incidence also was elevated, albeit not as dramatically – 7% by age 40 – among survivors who received 10-19 Gy of radiation.

Excess risk in those treated with 10-19 Gy warrants "consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with [more than] 20 Gy," the investigators concluded.

About 50,000 survivors received 20 Gy or more of radiation and, therefore, meet the current threshold, Dr. Moskowitz said. Lowering the threshold to include survivors who were treated with 10-19 Gy of chest radiation would add another 7,000-9,000 women.

Increasing public awareness is crucial to increasing surveillance. "Many women who were treated with chest radiation don’t know they have an increased risk of breast cancer," she said. "Their physicians may or may not know, but many physicians are not aware of the guidelines."

Moreover, many survivors don’t know their radiation exposure, and she urged them to try to find those records from long, long ago.

The analysis – a report from the Childhood Cancer Survivor Study (CCSS) and the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study – mined data on 1,268 women survivors of childhood cancers diagnosed from 1970 to 1986 and on 4,570 first-degree relatives of women who had survived at least 1 year after being diagnosed with breast cancer.

Median follow-up was 26 years in the childhood survivors, of whom 175 women were diagnosed with breast cancer as adults. Median latency was 23 years after treatment, and diagnosis was made at a median age of 38 years.

Multiple studies have shown an increased risk of breast cancer in women who received chest radiation as children, Dr. Moskowitz said. This large study has substantially longer follow-up and was surprising in the magnitude of risk it documents.

Chest radiation doses are lower today, and mantle field radiation – which had been used almost exclusively in Hodgkin’s lymphoma – is no longer used, but other regimens are still in the clinic, she added.

Another surprise from the study was that whole lung radiation, even at low doses, can heighten breast cancer risk. "Women treated with whole lung radiation have a risk of breast cancer that is higher than previous recognized and may benefit from surveillance strategies," she said.

"These are striking data and certainly warrant our careful attention," commented press briefing chair Dr. Nicholas Vogelzang, chair and medical director of the developmental therapeutics committee at the Comprehensive Cancer Centers of Nevada, Las Vegas, and cochair of the genitourinary committee for U.S. Oncology Research.

"The benefit of curing a cancer is you can live 25 or more years," he said, noting that curves for breast cancer incidence rose after 25 years in a graphic representation of the data presented. "We have an obligation to those many thousands of young women whom we treated many years ago."

The investigators said that they had no relevant financial disclosures.

CHICAGO – Breast cancer risk is much higher than previously recognized among women who received chest radiation for Hodgkin’s lymphoma when they were children, investigators reported.

By the time these survivors are 50 years of age, breast cancer incidence is 30% – "remarkably similar" to the 31% incidence observed in the high-risk group of women with BRCA1 mutations, Chaya S. Moskowitz, Ph.D., and her colleagues determined in a study presented at the annual meeting of the American Society of Clinical Oncology.

Although the effect was less dramatic, cumulative risk also was elevated in survivors of other childhood cancers treated with chest radiation, reaching 24% overall by age 50, Dr. Moskowitz said at a press briefing. Among the general population of women in the United States, it is 4% at that benchmark, she noted.

Particularly concerning is the heightened risk observed in women who received less radiation than the current threshold at which the Children’s Oncology Group (COG) recommends breast cancer surveillance. The COG says that survivors who received 20 Gy or more of chest radiation should start annual mammograms at age 25 years or 8 years after radiotherapy, whichever comes later.

In this group, 12% of survivors will develop breast cancer by age 40, said Dr. Moskowitz, a biostatistician at Memorial Sloan-Kettering Cancer Center in New York. The study showed that breast cancer incidence also was elevated, albeit not as dramatically – 7% by age 40 – among survivors who received 10-19 Gy of radiation.

Excess risk in those treated with 10-19 Gy warrants "consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with [more than] 20 Gy," the investigators concluded.

About 50,000 survivors received 20 Gy or more of radiation and, therefore, meet the current threshold, Dr. Moskowitz said. Lowering the threshold to include survivors who were treated with 10-19 Gy of chest radiation would add another 7,000-9,000 women.

Increasing public awareness is crucial to increasing surveillance. "Many women who were treated with chest radiation don’t know they have an increased risk of breast cancer," she said. "Their physicians may or may not know, but many physicians are not aware of the guidelines."

Moreover, many survivors don’t know their radiation exposure, and she urged them to try to find those records from long, long ago.

The analysis – a report from the Childhood Cancer Survivor Study (CCSS) and the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study – mined data on 1,268 women survivors of childhood cancers diagnosed from 1970 to 1986 and on 4,570 first-degree relatives of women who had survived at least 1 year after being diagnosed with breast cancer.

Median follow-up was 26 years in the childhood survivors, of whom 175 women were diagnosed with breast cancer as adults. Median latency was 23 years after treatment, and diagnosis was made at a median age of 38 years.

Multiple studies have shown an increased risk of breast cancer in women who received chest radiation as children, Dr. Moskowitz said. This large study has substantially longer follow-up and was surprising in the magnitude of risk it documents.

Chest radiation doses are lower today, and mantle field radiation – which had been used almost exclusively in Hodgkin’s lymphoma – is no longer used, but other regimens are still in the clinic, she added.

Another surprise from the study was that whole lung radiation, even at low doses, can heighten breast cancer risk. "Women treated with whole lung radiation have a risk of breast cancer that is higher than previous recognized and may benefit from surveillance strategies," she said.

"These are striking data and certainly warrant our careful attention," commented press briefing chair Dr. Nicholas Vogelzang, chair and medical director of the developmental therapeutics committee at the Comprehensive Cancer Centers of Nevada, Las Vegas, and cochair of the genitourinary committee for U.S. Oncology Research.

"The benefit of curing a cancer is you can live 25 or more years," he said, noting that curves for breast cancer incidence rose after 25 years in a graphic representation of the data presented. "We have an obligation to those many thousands of young women whom we treated many years ago."

The investigators said that they had no relevant financial disclosures.

CHICAGO – Enjoying periodic breaks from hormonal therapy can take years off the life of a man with metastatic prostate cancer, according to results of the largest and longest clinical trial comparing intermittent androgen deprivation with continuous therapy.

The data are expected to squelch the use of intermittent androgen therapy (IAD) in men seeking quality-of-life improvements without reducing the efficacy of treatment for advanced disease. Previous studies suggested no harm would be done, but up to now physicians did not have a definitive comparison with continuous androgen deprivation (CAD).

Patrice Wendling/IMNG Medical Media

"This study for the first time demonstrates that there is a price to pay, and in the patients most likely to receive intermittent therapy in this country and around the world, the minimal disease patients, it is almost 2 years’ median survival. So I think that is an important fact," said Dr. Bruce J. Roth, moderator of a press briefing at the American Society of Clinical Oncology annual meeting, where the outcomes were presented in a plenary session on Sunday, June 3.

The greatest impact was seen in men with minimal disease, who lived a median of 5.2 years if randomized to intermittent therapy vs. 7.1 years with continuous treatment, according to Dr. Maha Hussain, the lead author. Half of the men in the continuous arm, but only 42% on intermittent therapy, were alive at 7 years in the phase III intergroup study led by the Southwest Oncology Group (SWOG).

Men with extensive disease fared no worse on IAD – their median overall survival reached 5 years vs. 4.4 years among those on CAD. The investigators found this "striking and surprising because it goes against conventional belief based on all the trials that have been done thus far with this disease," said Dr. Hussain, a professor of medicine and urology at the University of Michigan Comprehensive Cancer Center in Ann Arbor. A third of these men were alive at 7 years, regardless of which regimen they received.

Photo Jane S. MacNeil/IMNG Medical Media

Overall, IAD did not meet the standard of non-inferiority to CAD, Dr. Hussain emphasized. At a median 9.2 years of follow-up, men randomized to CAD lived a median of 5.8 years vs. 5.1 years with IAD.

"Because of these findings continuous therapy continues to be the standard of care," said Dr. Hussain; IAD was not inferior to CAD in patients with extensive disease, but it was "significantly inferior" in men with minimal disease. "These observations suggest inherent biological differences and warrant further evaluations."

Asked whether she might recommend IAD in men with extensive disease, she cautioned that the data in this group came from a secondary analysis and are not understood. Moreover, many new therapies are emerging, giving more options to men with metastatic prostate cancer.

The trial used a nonstandard definition of extensive disease and the subset analysis was not "preplanned," Dr. William K. Oh said, dismissing the extensive disease finding in a plenary session discussion of the presentation.*

Overall, he called the trial a "Herculean effort" and noted that, unlike many previous studies, it was adequately powered to determine overall survival. Preclinical mouse studies that suggested IAD might delay time to castration resistance should no longer be cited as a rationale for IAD, he added.

"Neither this nor any randomized trial has ever shown a superior outcome with intermittent ADT [androgen deprivation therapy]," said Dr. Oh, chief of the Division of Hematology and Medical Oncology at Mt. Sinai Medical Center in New York.

"Continuous ADT remains the standard of care for all patients with metastatic prostate cancer," he concluded, allowing that it might still be considered in patients with nonmetastatic rising PSA.

The trial was started in 1995; at that time median survival was 2.5 – 3 years, and physicians hoped that intermittent therapy could relieve side effects impinging on quality of life. Based on experimental data, investigators hypothesized that delivering less drug over time might delay resistance to hormonal therapy. The non-inferiority trial design required that the investigators could rule out a 20% or greater relative increase in risk of death with a 95% confidence interval.

Dr. Hussain, Dr. Roth, and Dr. Oh offered a number of reasons why the non-inferiority trial revealed a negative impact that was not seen in the previous studies.

Notably, the SWOG 9346 (Intergroup -0162) trial was larger, involving 5 cancer research groups in the United States, Canada, and Europe. They accrued 3,040 patients with newly diagnosed metastatic prostate cancer and a PSA of at least 5 by 2008.

In addition, the trial randomized only men with newly metastatic disease who had achieved a PSA of 4.0 or less after 7 months of CAD with goserelin and bicalutamide – starting 770 patients on IAD and continuing 759 patients to CAD. The median age was 70, about half (48%) had extensive disease, and 14% were African Americans. Men on IAD were monitored monthly and went back on therapy based on predetermined parameters.

If PSA rose to 20 ng/ml in men on IAD or to a pre-registration baseline below 20 ng/ml, therapy was restarted; it could also be restarted based on symptoms. After 7 months, men could take another break if their PSA normalized. An increase to greater than 4 ng/ml on months 6 or 7 would send them back to continuous therapy until progression.

Previous studies enrolled populations with earlier stage disease before physicians could determine whether they were responsive to hormone therapy or not, noted Dr. Roth, professor of medicine in the division of oncology at Washington University School of Medicine. The men in this trial "were the most likely to benefit from hormone therapy."

While the number of men trying IAD is not known, it is used in the United States, Dr. Roth said. He does not offer it to his patients – and will not offer it going forward – but often sees it in the charts of patients referred to him.

"A 2-year difference in median survival is huge," he said, predicting patients would not press for IAD once they discussed the research with their physicians.

"Are you going to trade off hot flashes for a 2-year decrease in median overall survival with IAD?" he proposed asking a patient. "I think the average patient will say, ‘Those hot flashes are not so bad.’"

The investigators disclosed numerous relationships with pharmaceutical companies.

* This story was updated with additional analysis from Dr. Oh on 6/6/2012.

CHICAGO – Enjoying periodic breaks from hormonal therapy can take years off the life of a man with metastatic prostate cancer, according to results of the largest and longest clinical trial comparing intermittent androgen deprivation with continuous therapy.

The data are expected to squelch the use of intermittent androgen therapy (IAD) in men seeking quality-of-life improvements without reducing the efficacy of treatment for advanced disease. Previous studies suggested no harm would be done, but up to now physicians did not have a definitive comparison with continuous androgen deprivation (CAD).

Patrice Wendling/IMNG Medical Media

"This study for the first time demonstrates that there is a price to pay, and in the patients most likely to receive intermittent therapy in this country and around the world, the minimal disease patients, it is almost 2 years’ median survival. So I think that is an important fact," said Dr. Bruce J. Roth, moderator of a press briefing at the American Society of Clinical Oncology annual meeting, where the outcomes were presented in a plenary session on Sunday, June 3.

The greatest impact was seen in men with minimal disease, who lived a median of 5.2 years if randomized to intermittent therapy vs. 7.1 years with continuous treatment, according to Dr. Maha Hussain, the lead author. Half of the men in the continuous arm, but only 42% on intermittent therapy, were alive at 7 years in the phase III intergroup study led by the Southwest Oncology Group (SWOG).

Men with extensive disease fared no worse on IAD – their median overall survival reached 5 years vs. 4.4 years among those on CAD. The investigators found this "striking and surprising because it goes against conventional belief based on all the trials that have been done thus far with this disease," said Dr. Hussain, a professor of medicine and urology at the University of Michigan Comprehensive Cancer Center in Ann Arbor. A third of these men were alive at 7 years, regardless of which regimen they received.

Photo Jane S. MacNeil/IMNG Medical Media

Overall, IAD did not meet the standard of non-inferiority to CAD, Dr. Hussain emphasized. At a median 9.2 years of follow-up, men randomized to CAD lived a median of 5.8 years vs. 5.1 years with IAD.

"Because of these findings continuous therapy continues to be the standard of care," said Dr. Hussain; IAD was not inferior to CAD in patients with extensive disease, but it was "significantly inferior" in men with minimal disease. "These observations suggest inherent biological differences and warrant further evaluations."

Asked whether she might recommend IAD in men with extensive disease, she cautioned that the data in this group came from a secondary analysis and are not understood. Moreover, many new therapies are emerging, giving more options to men with metastatic prostate cancer.

The trial used a nonstandard definition of extensive disease and the subset analysis was not "preplanned," Dr. William K. Oh said, dismissing the extensive disease finding in a plenary session discussion of the presentation.*

Overall, he called the trial a "Herculean effort" and noted that, unlike many previous studies, it was adequately powered to determine overall survival. Preclinical mouse studies that suggested IAD might delay time to castration resistance should no longer be cited as a rationale for IAD, he added.

"Neither this nor any randomized trial has ever shown a superior outcome with intermittent ADT [androgen deprivation therapy]," said Dr. Oh, chief of the Division of Hematology and Medical Oncology at Mt. Sinai Medical Center in New York.

"Continuous ADT remains the standard of care for all patients with metastatic prostate cancer," he concluded, allowing that it might still be considered in patients with nonmetastatic rising PSA.

The trial was started in 1995; at that time median survival was 2.5 – 3 years, and physicians hoped that intermittent therapy could relieve side effects impinging on quality of life. Based on experimental data, investigators hypothesized that delivering less drug over time might delay resistance to hormonal therapy. The non-inferiority trial design required that the investigators could rule out a 20% or greater relative increase in risk of death with a 95% confidence interval.

Dr. Hussain, Dr. Roth, and Dr. Oh offered a number of reasons why the non-inferiority trial revealed a negative impact that was not seen in the previous studies.

Notably, the SWOG 9346 (Intergroup -0162) trial was larger, involving 5 cancer research groups in the United States, Canada, and Europe. They accrued 3,040 patients with newly diagnosed metastatic prostate cancer and a PSA of at least 5 by 2008.

In addition, the trial randomized only men with newly metastatic disease who had achieved a PSA of 4.0 or less after 7 months of CAD with goserelin and bicalutamide – starting 770 patients on IAD and continuing 759 patients to CAD. The median age was 70, about half (48%) had extensive disease, and 14% were African Americans. Men on IAD were monitored monthly and went back on therapy based on predetermined parameters.

If PSA rose to 20 ng/ml in men on IAD or to a pre-registration baseline below 20 ng/ml, therapy was restarted; it could also be restarted based on symptoms. After 7 months, men could take another break if their PSA normalized. An increase to greater than 4 ng/ml on months 6 or 7 would send them back to continuous therapy until progression.

Previous studies enrolled populations with earlier stage disease before physicians could determine whether they were responsive to hormone therapy or not, noted Dr. Roth, professor of medicine in the division of oncology at Washington University School of Medicine. The men in this trial "were the most likely to benefit from hormone therapy."

While the number of men trying IAD is not known, it is used in the United States, Dr. Roth said. He does not offer it to his patients – and will not offer it going forward – but often sees it in the charts of patients referred to him.

"A 2-year difference in median survival is huge," he said, predicting patients would not press for IAD once they discussed the research with their physicians.

"Are you going to trade off hot flashes for a 2-year decrease in median overall survival with IAD?" he proposed asking a patient. "I think the average patient will say, ‘Those hot flashes are not so bad.’"

The investigators disclosed numerous relationships with pharmaceutical companies.

* This story was updated with additional analysis from Dr. Oh on 6/6/2012.

CHICAGO – Enjoying periodic breaks from hormonal therapy can take years off the life of a man with metastatic prostate cancer, according to results of the largest and longest clinical trial comparing intermittent androgen deprivation with continuous therapy.

The data are expected to squelch the use of intermittent androgen therapy (IAD) in men seeking quality-of-life improvements without reducing the efficacy of treatment for advanced disease. Previous studies suggested no harm would be done, but up to now physicians did not have a definitive comparison with continuous androgen deprivation (CAD).

Patrice Wendling/IMNG Medical Media

"This study for the first time demonstrates that there is a price to pay, and in the patients most likely to receive intermittent therapy in this country and around the world, the minimal disease patients, it is almost 2 years’ median survival. So I think that is an important fact," said Dr. Bruce J. Roth, moderator of a press briefing at the American Society of Clinical Oncology annual meeting, where the outcomes were presented in a plenary session on Sunday, June 3.

The greatest impact was seen in men with minimal disease, who lived a median of 5.2 years if randomized to intermittent therapy vs. 7.1 years with continuous treatment, according to Dr. Maha Hussain, the lead author. Half of the men in the continuous arm, but only 42% on intermittent therapy, were alive at 7 years in the phase III intergroup study led by the Southwest Oncology Group (SWOG).

Men with extensive disease fared no worse on IAD – their median overall survival reached 5 years vs. 4.4 years among those on CAD. The investigators found this "striking and surprising because it goes against conventional belief based on all the trials that have been done thus far with this disease," said Dr. Hussain, a professor of medicine and urology at the University of Michigan Comprehensive Cancer Center in Ann Arbor. A third of these men were alive at 7 years, regardless of which regimen they received.

Photo Jane S. MacNeil/IMNG Medical Media

Overall, IAD did not meet the standard of non-inferiority to CAD, Dr. Hussain emphasized. At a median 9.2 years of follow-up, men randomized to CAD lived a median of 5.8 years vs. 5.1 years with IAD.

"Because of these findings continuous therapy continues to be the standard of care," said Dr. Hussain; IAD was not inferior to CAD in patients with extensive disease, but it was "significantly inferior" in men with minimal disease. "These observations suggest inherent biological differences and warrant further evaluations."

Asked whether she might recommend IAD in men with extensive disease, she cautioned that the data in this group came from a secondary analysis and are not understood. Moreover, many new therapies are emerging, giving more options to men with metastatic prostate cancer.

The trial used a nonstandard definition of extensive disease and the subset analysis was not "preplanned," Dr. William K. Oh said, dismissing the extensive disease finding in a plenary session discussion of the presentation.*

Overall, he called the trial a "Herculean effort" and noted that, unlike many previous studies, it was adequately powered to determine overall survival. Preclinical mouse studies that suggested IAD might delay time to castration resistance should no longer be cited as a rationale for IAD, he added.

"Neither this nor any randomized trial has ever shown a superior outcome with intermittent ADT [androgen deprivation therapy]," said Dr. Oh, chief of the Division of Hematology and Medical Oncology at Mt. Sinai Medical Center in New York.

"Continuous ADT remains the standard of care for all patients with metastatic prostate cancer," he concluded, allowing that it might still be considered in patients with nonmetastatic rising PSA.

The trial was started in 1995; at that time median survival was 2.5 – 3 years, and physicians hoped that intermittent therapy could relieve side effects impinging on quality of life. Based on experimental data, investigators hypothesized that delivering less drug over time might delay resistance to hormonal therapy. The non-inferiority trial design required that the investigators could rule out a 20% or greater relative increase in risk of death with a 95% confidence interval.

Dr. Hussain, Dr. Roth, and Dr. Oh offered a number of reasons why the non-inferiority trial revealed a negative impact that was not seen in the previous studies.

Notably, the SWOG 9346 (Intergroup -0162) trial was larger, involving 5 cancer research groups in the United States, Canada, and Europe. They accrued 3,040 patients with newly diagnosed metastatic prostate cancer and a PSA of at least 5 by 2008.

In addition, the trial randomized only men with newly metastatic disease who had achieved a PSA of 4.0 or less after 7 months of CAD with goserelin and bicalutamide – starting 770 patients on IAD and continuing 759 patients to CAD. The median age was 70, about half (48%) had extensive disease, and 14% were African Americans. Men on IAD were monitored monthly and went back on therapy based on predetermined parameters.

If PSA rose to 20 ng/ml in men on IAD or to a pre-registration baseline below 20 ng/ml, therapy was restarted; it could also be restarted based on symptoms. After 7 months, men could take another break if their PSA normalized. An increase to greater than 4 ng/ml on months 6 or 7 would send them back to continuous therapy until progression.

Previous studies enrolled populations with earlier stage disease before physicians could determine whether they were responsive to hormone therapy or not, noted Dr. Roth, professor of medicine in the division of oncology at Washington University School of Medicine. The men in this trial "were the most likely to benefit from hormone therapy."

While the number of men trying IAD is not known, it is used in the United States, Dr. Roth said. He does not offer it to his patients – and will not offer it going forward – but often sees it in the charts of patients referred to him.

"A 2-year difference in median survival is huge," he said, predicting patients would not press for IAD once they discussed the research with their physicians.

"Are you going to trade off hot flashes for a 2-year decrease in median overall survival with IAD?" he proposed asking a patient. "I think the average patient will say, ‘Those hot flashes are not so bad.’"

The investigators disclosed numerous relationships with pharmaceutical companies.

* This story was updated with additional analysis from Dr. Oh on 6/6/2012.

CHICAGO – Putting adolescent and young adult leukemia patients on pediatric regimens improved their event-free survival rate at 5-years, but they still did not fare as well as younger patients in a clinical study.

The Children’s Oncology Group protocol randomized 2,571 patients up to 30 years of age in a comparison of treatment regimens for high-risk B-precursor acute lymphoblastic leukemia (ALL). Within this population, 501 patients were 16 years or older – an age group that historically has had poorer outcomes than younger patients.

The 5-year event-free survival rate reached 68% among adolescent and young adult (AYA) patients in the randomized phase III trial – better than the 50%-60% consistently reported in previous trials, according to Dr. Eric Larsen, lead author of the study. It fell short of the 80% achieved in younger patients, however (P less than .0001).

The AYA cohort also had lower rates of overall survival (79.8% vs. 88.4%; P less than .0001) and remission (97.2% vs. 98.8%; P = .0134), which investigators defined as less than 5% marrow blasts after induction therapy. They blamed the disparity in large part on a higher rate of marrow relapse in the older patients (15.2% vs. 9.0%; P less than .0007). CNS relapse occurred at a slightly higher rate in the AYA group – 5.2% vs. 3.7%, they noted, but the difference was not significant (P = .5776).

In another comparison, the AYA patients were more likely to relapse – the 5-year cumulative incidence was 21.3% vs. 13.4% for younger patients (P = .0018). Though induction mortality rates were not significantly different between AYA and younger patients, (2.4% vs. 1.8%; P = .36), postinduction remission deaths were significantly higher at 5 years (5.5% vs. 2.1%; P less than .0001).

After 5 years, survival curves tend to flatten for both age groups but remissions are still possible, Dr. Larsen said, underscoring the importance of the benchmark during a press briefing at the annual meeting of the American Society of Clinical Oncology.

"In clinical practice and in the research world we would never declare someone truly cured, but when you are out 5 years, the number of people who are going to relapse is extraordinarily small," he said.

Dr. Larsen, medical director of the Maine Children’s Cancer Program, Scarborough, and study chair of the Children’s Oncology Group protocol AALL0232, presented the analysis June 2 at the society’s annual meeting. He reported outcomes of the trial – it found that giving patients 50 times the standard methotrexate dose reduces recurrences – last year at ASCO.

The study was the first pediatric ALL trial to include patients up to 30 years, he noted. Typically, pediatric studies enroll patients up to 18 years of age, but investigators hoped to improve the outcomes of the AYA age group by delivering more aggressive regimens than are typically used in adult patients.

"This is an underserved area," commented Dr. Carol Aghajanian, moderator of the news briefing and chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York.

"I do see young adults ... who have pediatric tumors," she said in an interview. "Do I treat them as a typical adult or as a child who is much younger? We have this group that gets lost in the middle because of their unique situation.

"We need to identify these patients and do studies that define the biology of their disease [and] what the right treatments are," she added.

What the current analysis has shown is that "future strategies to improve outcome in AYA patients with ALL should focus on both better leukemia control and reduced treatment toxicity," Dr. Larsen said in a summary of the findings. AYA patients "have more resistant leukemia and they are more susceptible to side effects," he added in an interview.

Many factors are thought to contribute to the poorer outcomes in AYA patients, according to Dr. Larsen. These include differences in disease biology leading to more aggressive cancers and less tolerance of chemotherapy side effects than is seen in pediatric patients. In addition, socioeconomic factors may be involved, as AYA patients are often in college or looking for jobs.

Compliance is an issue as well, he noted. Although parents take charge of administering oral medications for their children, teenagers want to be responsible for themselves – sometimes with less than optimal results.

"It’s pretty clear that adolescent patients have lower rates of compliance," Dr. Larsen said, adding that "lower compliances correlates with lower survival rates."

The authors said that they had no disclosures.

CHICAGO – Putting adolescent and young adult leukemia patients on pediatric regimens improved their event-free survival rate at 5-years, but they still did not fare as well as younger patients in a clinical study.

The Children’s Oncology Group protocol randomized 2,571 patients up to 30 years of age in a comparison of treatment regimens for high-risk B-precursor acute lymphoblastic leukemia (ALL). Within this population, 501 patients were 16 years or older – an age group that historically has had poorer outcomes than younger patients.

The 5-year event-free survival rate reached 68% among adolescent and young adult (AYA) patients in the randomized phase III trial – better than the 50%-60% consistently reported in previous trials, according to Dr. Eric Larsen, lead author of the study. It fell short of the 80% achieved in younger patients, however (P less than .0001).

The AYA cohort also had lower rates of overall survival (79.8% vs. 88.4%; P less than .0001) and remission (97.2% vs. 98.8%; P = .0134), which investigators defined as less than 5% marrow blasts after induction therapy. They blamed the disparity in large part on a higher rate of marrow relapse in the older patients (15.2% vs. 9.0%; P less than .0007). CNS relapse occurred at a slightly higher rate in the AYA group – 5.2% vs. 3.7%, they noted, but the difference was not significant (P = .5776).

In another comparison, the AYA patients were more likely to relapse – the 5-year cumulative incidence was 21.3% vs. 13.4% for younger patients (P = .0018). Though induction mortality rates were not significantly different between AYA and younger patients, (2.4% vs. 1.8%; P = .36), postinduction remission deaths were significantly higher at 5 years (5.5% vs. 2.1%; P less than .0001).

After 5 years, survival curves tend to flatten for both age groups but remissions are still possible, Dr. Larsen said, underscoring the importance of the benchmark during a press briefing at the annual meeting of the American Society of Clinical Oncology.

"In clinical practice and in the research world we would never declare someone truly cured, but when you are out 5 years, the number of people who are going to relapse is extraordinarily small," he said.

Dr. Larsen, medical director of the Maine Children’s Cancer Program, Scarborough, and study chair of the Children’s Oncology Group protocol AALL0232, presented the analysis June 2 at the society’s annual meeting. He reported outcomes of the trial – it found that giving patients 50 times the standard methotrexate dose reduces recurrences – last year at ASCO.

The study was the first pediatric ALL trial to include patients up to 30 years, he noted. Typically, pediatric studies enroll patients up to 18 years of age, but investigators hoped to improve the outcomes of the AYA age group by delivering more aggressive regimens than are typically used in adult patients.

"This is an underserved area," commented Dr. Carol Aghajanian, moderator of the news briefing and chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York.

"I do see young adults ... who have pediatric tumors," she said in an interview. "Do I treat them as a typical adult or as a child who is much younger? We have this group that gets lost in the middle because of their unique situation.

"We need to identify these patients and do studies that define the biology of their disease [and] what the right treatments are," she added.

What the current analysis has shown is that "future strategies to improve outcome in AYA patients with ALL should focus on both better leukemia control and reduced treatment toxicity," Dr. Larsen said in a summary of the findings. AYA patients "have more resistant leukemia and they are more susceptible to side effects," he added in an interview.

Many factors are thought to contribute to the poorer outcomes in AYA patients, according to Dr. Larsen. These include differences in disease biology leading to more aggressive cancers and less tolerance of chemotherapy side effects than is seen in pediatric patients. In addition, socioeconomic factors may be involved, as AYA patients are often in college or looking for jobs.

Compliance is an issue as well, he noted. Although parents take charge of administering oral medications for their children, teenagers want to be responsible for themselves – sometimes with less than optimal results.

"It’s pretty clear that adolescent patients have lower rates of compliance," Dr. Larsen said, adding that "lower compliances correlates with lower survival rates."

The authors said that they had no disclosures.

CHICAGO – Putting adolescent and young adult leukemia patients on pediatric regimens improved their event-free survival rate at 5-years, but they still did not fare as well as younger patients in a clinical study.

The Children’s Oncology Group protocol randomized 2,571 patients up to 30 years of age in a comparison of treatment regimens for high-risk B-precursor acute lymphoblastic leukemia (ALL). Within this population, 501 patients were 16 years or older – an age group that historically has had poorer outcomes than younger patients.

The 5-year event-free survival rate reached 68% among adolescent and young adult (AYA) patients in the randomized phase III trial – better than the 50%-60% consistently reported in previous trials, according to Dr. Eric Larsen, lead author of the study. It fell short of the 80% achieved in younger patients, however (P less than .0001).

The AYA cohort also had lower rates of overall survival (79.8% vs. 88.4%; P less than .0001) and remission (97.2% vs. 98.8%; P = .0134), which investigators defined as less than 5% marrow blasts after induction therapy. They blamed the disparity in large part on a higher rate of marrow relapse in the older patients (15.2% vs. 9.0%; P less than .0007). CNS relapse occurred at a slightly higher rate in the AYA group – 5.2% vs. 3.7%, they noted, but the difference was not significant (P = .5776).

In another comparison, the AYA patients were more likely to relapse – the 5-year cumulative incidence was 21.3% vs. 13.4% for younger patients (P = .0018). Though induction mortality rates were not significantly different between AYA and younger patients, (2.4% vs. 1.8%; P = .36), postinduction remission deaths were significantly higher at 5 years (5.5% vs. 2.1%; P less than .0001).

After 5 years, survival curves tend to flatten for both age groups but remissions are still possible, Dr. Larsen said, underscoring the importance of the benchmark during a press briefing at the annual meeting of the American Society of Clinical Oncology.

"In clinical practice and in the research world we would never declare someone truly cured, but when you are out 5 years, the number of people who are going to relapse is extraordinarily small," he said.

Dr. Larsen, medical director of the Maine Children’s Cancer Program, Scarborough, and study chair of the Children’s Oncology Group protocol AALL0232, presented the analysis June 2 at the society’s annual meeting. He reported outcomes of the trial – it found that giving patients 50 times the standard methotrexate dose reduces recurrences – last year at ASCO.

The study was the first pediatric ALL trial to include patients up to 30 years, he noted. Typically, pediatric studies enroll patients up to 18 years of age, but investigators hoped to improve the outcomes of the AYA age group by delivering more aggressive regimens than are typically used in adult patients.

"This is an underserved area," commented Dr. Carol Aghajanian, moderator of the news briefing and chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York.

"I do see young adults ... who have pediatric tumors," she said in an interview. "Do I treat them as a typical adult or as a child who is much younger? We have this group that gets lost in the middle because of their unique situation.

"We need to identify these patients and do studies that define the biology of their disease [and] what the right treatments are," she added.

What the current analysis has shown is that "future strategies to improve outcome in AYA patients with ALL should focus on both better leukemia control and reduced treatment toxicity," Dr. Larsen said in a summary of the findings. AYA patients "have more resistant leukemia and they are more susceptible to side effects," he added in an interview.

Many factors are thought to contribute to the poorer outcomes in AYA patients, according to Dr. Larsen. These include differences in disease biology leading to more aggressive cancers and less tolerance of chemotherapy side effects than is seen in pediatric patients. In addition, socioeconomic factors may be involved, as AYA patients are often in college or looking for jobs.

Compliance is an issue as well, he noted. Although parents take charge of administering oral medications for their children, teenagers want to be responsible for themselves – sometimes with less than optimal results.

"It’s pretty clear that adolescent patients have lower rates of compliance," Dr. Larsen said, adding that "lower compliances correlates with lower survival rates."

The authors said that they had no disclosures.

Daily aspirin reduced the risk of recurrent blood clots significantly for patients who had stopped anticoagulant therapy after a first unprovoked venous thromboembolism, investigators reported in the New England Journal of Medicine.

About a 40% reduction was accomplished without an increase in major bleeding, in the 402-patient Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) study. Adverse events were similar whether patients were randomized to 100 mg of aspirin daily or placebo.

©jimdeli/Fotolia.com

New blood clots occurred at a rate of 6.6% per year in patients randomized to aspirin, compared with 11.2% per year in those given placebo, Dr. Cecilia Becattini and her associates reported. At a median treatment period of 23.9 months, the recurrence rates while taking the study drug were 5.9% and 11.0% per year, respectively, with 1 patient in each group having a major bleed (N. Engl. J. Med. 366;21:1959-67).

All patients had completed 6-18 months of oral anticoagulant treatment with a vitamin K antagonist before randomization in the multicenter, double-blind trial. Patients were not enrolled if they had cancer, thrombophilia, or bleeding during the period of anticoagulant treatment, but the authors wrote that they "estimate that a substantial proportion (probably the majority) of patients with an initial episode of venous thromboembolism would be eligible for aspirin therapy as secondary prevention."

Dr. Becattini of the University of Perugia (Italy) presented results in December 2011 at the annual meeting of the American Society of Hematology. (Click here for our report, including a video interview with Dr. Becattini.)

The trial received support from the University of Perugia, a grant-in-aid from Bayer HealthCare, and an Aventis Fellowship for Clinical Research from the International Society of Thrombosis and Haemostasis (to Dr. Becattini). Dr. Becattini and several coauthors disclosed relationships with various drug companies, including Bayer.

Daily aspirin reduced the risk of recurrent blood clots significantly for patients who had stopped anticoagulant therapy after a first unprovoked venous thromboembolism, investigators reported in the New England Journal of Medicine.

About a 40% reduction was accomplished without an increase in major bleeding, in the 402-patient Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) study. Adverse events were similar whether patients were randomized to 100 mg of aspirin daily or placebo.

©jimdeli/Fotolia.com

New blood clots occurred at a rate of 6.6% per year in patients randomized to aspirin, compared with 11.2% per year in those given placebo, Dr. Cecilia Becattini and her associates reported. At a median treatment period of 23.9 months, the recurrence rates while taking the study drug were 5.9% and 11.0% per year, respectively, with 1 patient in each group having a major bleed (N. Engl. J. Med. 366;21:1959-67).

All patients had completed 6-18 months of oral anticoagulant treatment with a vitamin K antagonist before randomization in the multicenter, double-blind trial. Patients were not enrolled if they had cancer, thrombophilia, or bleeding during the period of anticoagulant treatment, but the authors wrote that they "estimate that a substantial proportion (probably the majority) of patients with an initial episode of venous thromboembolism would be eligible for aspirin therapy as secondary prevention."

Dr. Becattini of the University of Perugia (Italy) presented results in December 2011 at the annual meeting of the American Society of Hematology. (Click here for our report, including a video interview with Dr. Becattini.)

The trial received support from the University of Perugia, a grant-in-aid from Bayer HealthCare, and an Aventis Fellowship for Clinical Research from the International Society of Thrombosis and Haemostasis (to Dr. Becattini). Dr. Becattini and several coauthors disclosed relationships with various drug companies, including Bayer.

Daily aspirin reduced the risk of recurrent blood clots significantly for patients who had stopped anticoagulant therapy after a first unprovoked venous thromboembolism, investigators reported in the New England Journal of Medicine.

About a 40% reduction was accomplished without an increase in major bleeding, in the 402-patient Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) study. Adverse events were similar whether patients were randomized to 100 mg of aspirin daily or placebo.

©jimdeli/Fotolia.com

New blood clots occurred at a rate of 6.6% per year in patients randomized to aspirin, compared with 11.2% per year in those given placebo, Dr. Cecilia Becattini and her associates reported. At a median treatment period of 23.9 months, the recurrence rates while taking the study drug were 5.9% and 11.0% per year, respectively, with 1 patient in each group having a major bleed (N. Engl. J. Med. 366;21:1959-67).

All patients had completed 6-18 months of oral anticoagulant treatment with a vitamin K antagonist before randomization in the multicenter, double-blind trial. Patients were not enrolled if they had cancer, thrombophilia, or bleeding during the period of anticoagulant treatment, but the authors wrote that they "estimate that a substantial proportion (probably the majority) of patients with an initial episode of venous thromboembolism would be eligible for aspirin therapy as secondary prevention."

Dr. Becattini of the University of Perugia (Italy) presented results in December 2011 at the annual meeting of the American Society of Hematology. (Click here for our report, including a video interview with Dr. Becattini.)

The trial received support from the University of Perugia, a grant-in-aid from Bayer HealthCare, and an Aventis Fellowship for Clinical Research from the International Society of Thrombosis and Haemostasis (to Dr. Becattini). Dr. Becattini and several coauthors disclosed relationships with various drug companies, including Bayer.

Lenalidomide maintenance therapy delayed recurrences significantly when given to patients newly diagnosed with multiple myeloma in a trio of clinical trials that reported much-anticipated outcomes May 9 in the New England Journal of Medicine.

Only one trial showed a gain in overall survival, however, and the prospect of lenalidomide (Revlimid) maintenance becoming a standard of care remains uncertain despite the substantial benefit clearly demonstrated in these multicenter, double-blind, placebo-controlled phase III studies.

Notably, investigators reported that prolonged administration of lenalidomide was associated with an increased incidence of second cancers in patients who had undergone stem cell transplantation. This led the Food and Drug Administration to add a warning to the drug’s label on May 7 after a yearlong analysis of early data from the trials.

In addition, a bevy of new drugs, both approved and in the pipeline, has changed the course of multiple myeloma from one with a short life expectancy to that of a chronic disease, with most patients embarking on second-line therapies after experiencing recurrences within 3 years of initial treatment.

"It remains to be determined whether the incorporation of other new agents with lenalidomide will further increase the time to disease progression and overall survival," Dr. Philip L. McCarthy and his coauthors wrote at the conclusion of their report on the one trial that showed a benefit in overall survival.

Two trials compared maintenance lenalidomide with placebo in patients who achieved stable disease or better after stem cell transplantation. The third trial focused on an older group of patients that was not eligible for transplantation. All were stopped early after achieving their goals.

Crossover Did Not Erase Benefit

The Cancer and Leukemia Group B (CALGB) trial reported by Dr. McCarthy, of the Roswell Park Cancer Institute in Buffalo, N.Y., and his associates randomized 460 patients up to 70 years of age after stem cell transplantation. Patients in the lenalidomide arm started at 10 mg daily, and doses ranged from 5 to 15 mg until disease progression.

When the study was unblinded in December 2009, disease progression or death had occurred in 44% of the placebo group, but only 20% of patients on lenalidomide maintenance (hazard ratio, 0.37; P less than .001). Investigators reported that median time to progression was nearly twice as long with lenalidomide – 39 months vs. 21 months (P less than .001). At that point the study’s primary end point – time to progression – had been met, and 86 of 128 eligible patients in the placebo group began to receive lenalidomide maintenance.

Despite this crossover, lenalidomide maintenance continued to demonstrate a significant advantage at a median follow-up as of Oct. 31, 2011. By then, investigators reported, only 37% of the lenalidomide group had disease progression or death, compared with 58% of the placebo group (HR, 0.48). Median time to progression reached 46 months in the lenalidomide group vs. 27 months in the placebo arm (P less than .001), according to the new report.

The 3-year rate of freedom from progression or death was higher with lenalidomide maintenance (66% vs. 39%), as was the overall survival rate (88% vs. 80%, HR 0.62) (N. Engl. J. Med. 2012;366:1770-81).

Younger Group in IFM Trial

Dr. Michel Attal of Hôpital Purpan in Toulouse, France, and his colleagues from the Intergroupe Francophone du Myélome (IFM) conducted a similar trial in a population of 614 patients under age 65 whose disease had not progressed after stem cell transplantation. All patients received two 28-day cycles of consolidation treatment with lenalidomide (25 mg daily on days 121) followed by maintenance with placebo or lenalidomide (10 mg daily for 3 months, after which the dose could be increased to 15 mg if tolerated) until disease progression.

At the time the study was unblinded at a median follow-up of 30 months in July 2010, median progression-free survival was nearly twice as long with lenalidomide maintenance – 41 months, compared with 23 months with a placebo (HR, 0.50; P less than .001). Overall survival was similar between the groups, and neither group had reached median overall survival.

By October 2011, median follow-up from time of randomization had reached 45 months, and the probability of surviving without progression 4 years after randomization was still about double with lenalidomide: 43% vs. 22% (HR, 0.50; P less than .001).

The overall survival rate was still similar, however, at 73% with lenalidomide and 75% with placebo. These survival rates are high, the authors noted, and longer follow-up may show an advantage for lenalidomide maintenance.

"Together with the findings reported by McCarthy et al., our data support the use of lenalidomide maintenance therapy after high-dose chemotherapy and autologous hematopoietic stem-cell transplantation in patients with myeloma, but the impressive benefits must be weighed against the increased risks," said Dr. Attal and his coauthors (N. Engl. J. Med. 2012;366:1782-91).

Older Patients Ineligible for Transplant

Dr. Antonio Palumbo of the University of Turin, Italy, and his coinvestigators from the Multiple Myeloma-015 (MM-015) trial also explored continuous lenalidomide, but in a population of 459 patients aged 65 years and older who were not eligible for stem cell transplantation.

Patients were randomized to three groups: One group received induction therapy with melphalan, prednisone, and lenalidomide followed by lenalidomide maintenance (MPR-R); the second received MPR followed by placebo maintenance; and the third received only melphalan and prednisone (MP) followed by placebo. Investigators reported that about two-thirds of patients completed their induction regimens.

Median progression-free survival, the primary end point, was significantly longer in the group that received lenalidomide maintenance (31 months) than in the groups that received MPR with placebo (14 months) or MP without any lenalidomide in the induction and maintenance phases (13 months).

In a landmark analysis that looked at progression-free survival from the start of maintenance therapy, the median reached 26 months with lenalidomide vs. 7 months with placebo, with a hazard ratio of 0.34 for MPR-R vs. MPR (P less than .001).

Greater benefit was seen in patients 65-75 years of age, with median progression-free survival of 31 months with MPR-R, 15 months with MPR, and 12 months with MP. In patients over age 75, the medians were 19 months, 12 months, and 15 months, respectively.

Median overall survival at 3 years was not significantly different, reaching 70% with MPR-R, 62% with MPR, and 66% with MP.

"Altogether, these results confirm the benefits of maintenance therapy with respect to progression-free survival. The influence on overall survival remains unclear," concluded Dr. Palumbo and his coauthors (N. Engl. J. Med. 2012;366:1759-69).

Secondary Malignancies

In all three studies lenalidomide was associated with higher rates of secondary primary cancers.

• The rate was 8% in the lenalidomide group vs. 3% in the placebo group in the CALGB study.

• The IFM investigators calculated the incidence as 3.1 per 100 patient-years in their lenalidomide group vs. 1.2 per 100 patient-years with placebo (P = .002).

• In the MM-015 study, the 3-year rate was 7% with MPR-R, 7% with MPR, and 3% with MP. The increased risk was "mainly confined to acute myeloid leukemia or myelodysplastic syndromes, and is observed when lenalidomide is given with or after melphalan," the investigators wrote.

Other Adverse Events

Hematologic toxicity dominated the adverse event reports from all three studies.

• In the CALBG trial, grade 3 and 4 hematologic side effects were significantly more common with lenalidomide maintenance, as were grade 3 nonhematologic events. The most pronounced was neutropenia in 45% of the lenalidomide group vs. 15% of the placebo group (P less than .001).

• The IFM investigators also reported that grade 3 or 4 hematologic events were more frequent with lenalidomide than with placebo (58% vs. 23%, P less than .001), as were thromboembolic events (6% vs. 2%, P = .01).

• Similarly, the MM-015 group found that the most frequent adverse events were hematologic, with grade 4 neutropenia occurring in 35% of patients given lenalidomide. Nonhematologic events, including deep vein thrombosis, occurred at low rates, however, according to Dr. Palumbo and his coauthors. "Lenalidomide maintenance was associated with little evidence of cumulative toxic effects," they said.

How the safety profiles will influence adoption of lenalidomide maintenance is uncertain. "A major concern during maintenance therapy is toxicity that limits long-term use and the ability to receive future treatment after disease progression or that results in life-threatening disorders," noted Dr. McCarthy and his coauthors.

The National Cancer Institute supported the CALGB trial. Celgene, maker of lenalidomide, provided support for the IFM and MM-015 studies. The IFM trial also received support from the Programme Hospitalier de Recherche Clinique and the Swiss Group for Clinical Cancer Research (SAKK). Disclosure forms filed by individual investigators are posted at http://www.nejm.org.

Lenalidomide maintenance therapy delayed recurrences significantly when given to patients newly diagnosed with multiple myeloma in a trio of clinical trials that reported much-anticipated outcomes May 9 in the New England Journal of Medicine.

Only one trial showed a gain in overall survival, however, and the prospect of lenalidomide (Revlimid) maintenance becoming a standard of care remains uncertain despite the substantial benefit clearly demonstrated in these multicenter, double-blind, placebo-controlled phase III studies.

Notably, investigators reported that prolonged administration of lenalidomide was associated with an increased incidence of second cancers in patients who had undergone stem cell transplantation. This led the Food and Drug Administration to add a warning to the drug’s label on May 7 after a yearlong analysis of early data from the trials.

In addition, a bevy of new drugs, both approved and in the pipeline, has changed the course of multiple myeloma from one with a short life expectancy to that of a chronic disease, with most patients embarking on second-line therapies after experiencing recurrences within 3 years of initial treatment.

"It remains to be determined whether the incorporation of other new agents with lenalidomide will further increase the time to disease progression and overall survival," Dr. Philip L. McCarthy and his coauthors wrote at the conclusion of their report on the one trial that showed a benefit in overall survival.

Two trials compared maintenance lenalidomide with placebo in patients who achieved stable disease or better after stem cell transplantation. The third trial focused on an older group of patients that was not eligible for transplantation. All were stopped early after achieving their goals.

Crossover Did Not Erase Benefit

The Cancer and Leukemia Group B (CALGB) trial reported by Dr. McCarthy, of the Roswell Park Cancer Institute in Buffalo, N.Y., and his associates randomized 460 patients up to 70 years of age after stem cell transplantation. Patients in the lenalidomide arm started at 10 mg daily, and doses ranged from 5 to 15 mg until disease progression.

When the study was unblinded in December 2009, disease progression or death had occurred in 44% of the placebo group, but only 20% of patients on lenalidomide maintenance (hazard ratio, 0.37; P less than .001). Investigators reported that median time to progression was nearly twice as long with lenalidomide – 39 months vs. 21 months (P less than .001). At that point the study’s primary end point – time to progression – had been met, and 86 of 128 eligible patients in the placebo group began to receive lenalidomide maintenance.

Despite this crossover, lenalidomide maintenance continued to demonstrate a significant advantage at a median follow-up as of Oct. 31, 2011. By then, investigators reported, only 37% of the lenalidomide group had disease progression or death, compared with 58% of the placebo group (HR, 0.48). Median time to progression reached 46 months in the lenalidomide group vs. 27 months in the placebo arm (P less than .001), according to the new report.

The 3-year rate of freedom from progression or death was higher with lenalidomide maintenance (66% vs. 39%), as was the overall survival rate (88% vs. 80%, HR 0.62) (N. Engl. J. Med. 2012;366:1770-81).

Younger Group in IFM Trial

Dr. Michel Attal of Hôpital Purpan in Toulouse, France, and his colleagues from the Intergroupe Francophone du Myélome (IFM) conducted a similar trial in a population of 614 patients under age 65 whose disease had not progressed after stem cell transplantation. All patients received two 28-day cycles of consolidation treatment with lenalidomide (25 mg daily on days 121) followed by maintenance with placebo or lenalidomide (10 mg daily for 3 months, after which the dose could be increased to 15 mg if tolerated) until disease progression.

At the time the study was unblinded at a median follow-up of 30 months in July 2010, median progression-free survival was nearly twice as long with lenalidomide maintenance – 41 months, compared with 23 months with a placebo (HR, 0.50; P less than .001). Overall survival was similar between the groups, and neither group had reached median overall survival.

By October 2011, median follow-up from time of randomization had reached 45 months, and the probability of surviving without progression 4 years after randomization was still about double with lenalidomide: 43% vs. 22% (HR, 0.50; P less than .001).

The overall survival rate was still similar, however, at 73% with lenalidomide and 75% with placebo. These survival rates are high, the authors noted, and longer follow-up may show an advantage for lenalidomide maintenance.

"Together with the findings reported by McCarthy et al., our data support the use of lenalidomide maintenance therapy after high-dose chemotherapy and autologous hematopoietic stem-cell transplantation in patients with myeloma, but the impressive benefits must be weighed against the increased risks," said Dr. Attal and his coauthors (N. Engl. J. Med. 2012;366:1782-91).

Older Patients Ineligible for Transplant

Dr. Antonio Palumbo of the University of Turin, Italy, and his coinvestigators from the Multiple Myeloma-015 (MM-015) trial also explored continuous lenalidomide, but in a population of 459 patients aged 65 years and older who were not eligible for stem cell transplantation.

Patients were randomized to three groups: One group received induction therapy with melphalan, prednisone, and lenalidomide followed by lenalidomide maintenance (MPR-R); the second received MPR followed by placebo maintenance; and the third received only melphalan and prednisone (MP) followed by placebo. Investigators reported that about two-thirds of patients completed their induction regimens.

Median progression-free survival, the primary end point, was significantly longer in the group that received lenalidomide maintenance (31 months) than in the groups that received MPR with placebo (14 months) or MP without any lenalidomide in the induction and maintenance phases (13 months).

In a landmark analysis that looked at progression-free survival from the start of maintenance therapy, the median reached 26 months with lenalidomide vs. 7 months with placebo, with a hazard ratio of 0.34 for MPR-R vs. MPR (P less than .001).

Greater benefit was seen in patients 65-75 years of age, with median progression-free survival of 31 months with MPR-R, 15 months with MPR, and 12 months with MP. In patients over age 75, the medians were 19 months, 12 months, and 15 months, respectively.

Median overall survival at 3 years was not significantly different, reaching 70% with MPR-R, 62% with MPR, and 66% with MP.

"Altogether, these results confirm the benefits of maintenance therapy with respect to progression-free survival. The influence on overall survival remains unclear," concluded Dr. Palumbo and his coauthors (N. Engl. J. Med. 2012;366:1759-69).

Secondary Malignancies

In all three studies lenalidomide was associated with higher rates of secondary primary cancers.

• The rate was 8% in the lenalidomide group vs. 3% in the placebo group in the CALGB study.

• The IFM investigators calculated the incidence as 3.1 per 100 patient-years in their lenalidomide group vs. 1.2 per 100 patient-years with placebo (P = .002).

• In the MM-015 study, the 3-year rate was 7% with MPR-R, 7% with MPR, and 3% with MP. The increased risk was "mainly confined to acute myeloid leukemia or myelodysplastic syndromes, and is observed when lenalidomide is given with or after melphalan," the investigators wrote.

Other Adverse Events

Hematologic toxicity dominated the adverse event reports from all three studies.

• In the CALBG trial, grade 3 and 4 hematologic side effects were significantly more common with lenalidomide maintenance, as were grade 3 nonhematologic events. The most pronounced was neutropenia in 45% of the lenalidomide group vs. 15% of the placebo group (P less than .001).

• The IFM investigators also reported that grade 3 or 4 hematologic events were more frequent with lenalidomide than with placebo (58% vs. 23%, P less than .001), as were thromboembolic events (6% vs. 2%, P = .01).

• Similarly, the MM-015 group found that the most frequent adverse events were hematologic, with grade 4 neutropenia occurring in 35% of patients given lenalidomide. Nonhematologic events, including deep vein thrombosis, occurred at low rates, however, according to Dr. Palumbo and his coauthors. "Lenalidomide maintenance was associated with little evidence of cumulative toxic effects," they said.

How the safety profiles will influence adoption of lenalidomide maintenance is uncertain. "A major concern during maintenance therapy is toxicity that limits long-term use and the ability to receive future treatment after disease progression or that results in life-threatening disorders," noted Dr. McCarthy and his coauthors.

The National Cancer Institute supported the CALGB trial. Celgene, maker of lenalidomide, provided support for the IFM and MM-015 studies. The IFM trial also received support from the Programme Hospitalier de Recherche Clinique and the Swiss Group for Clinical Cancer Research (SAKK). Disclosure forms filed by individual investigators are posted at http://www.nejm.org.

Lenalidomide maintenance therapy delayed recurrences significantly when given to patients newly diagnosed with multiple myeloma in a trio of clinical trials that reported much-anticipated outcomes May 9 in the New England Journal of Medicine.

Only one trial showed a gain in overall survival, however, and the prospect of lenalidomide (Revlimid) maintenance becoming a standard of care remains uncertain despite the substantial benefit clearly demonstrated in these multicenter, double-blind, placebo-controlled phase III studies.

Notably, investigators reported that prolonged administration of lenalidomide was associated with an increased incidence of second cancers in patients who had undergone stem cell transplantation. This led the Food and Drug Administration to add a warning to the drug’s label on May 7 after a yearlong analysis of early data from the trials.

In addition, a bevy of new drugs, both approved and in the pipeline, has changed the course of multiple myeloma from one with a short life expectancy to that of a chronic disease, with most patients embarking on second-line therapies after experiencing recurrences within 3 years of initial treatment.

"It remains to be determined whether the incorporation of other new agents with lenalidomide will further increase the time to disease progression and overall survival," Dr. Philip L. McCarthy and his coauthors wrote at the conclusion of their report on the one trial that showed a benefit in overall survival.

Two trials compared maintenance lenalidomide with placebo in patients who achieved stable disease or better after stem cell transplantation. The third trial focused on an older group of patients that was not eligible for transplantation. All were stopped early after achieving their goals.

Crossover Did Not Erase Benefit

The Cancer and Leukemia Group B (CALGB) trial reported by Dr. McCarthy, of the Roswell Park Cancer Institute in Buffalo, N.Y., and his associates randomized 460 patients up to 70 years of age after stem cell transplantation. Patients in the lenalidomide arm started at 10 mg daily, and doses ranged from 5 to 15 mg until disease progression.

When the study was unblinded in December 2009, disease progression or death had occurred in 44% of the placebo group, but only 20% of patients on lenalidomide maintenance (hazard ratio, 0.37; P less than .001). Investigators reported that median time to progression was nearly twice as long with lenalidomide – 39 months vs. 21 months (P less than .001). At that point the study’s primary end point – time to progression – had been met, and 86 of 128 eligible patients in the placebo group began to receive lenalidomide maintenance.

Despite this crossover, lenalidomide maintenance continued to demonstrate a significant advantage at a median follow-up as of Oct. 31, 2011. By then, investigators reported, only 37% of the lenalidomide group had disease progression or death, compared with 58% of the placebo group (HR, 0.48). Median time to progression reached 46 months in the lenalidomide group vs. 27 months in the placebo arm (P less than .001), according to the new report.

The 3-year rate of freedom from progression or death was higher with lenalidomide maintenance (66% vs. 39%), as was the overall survival rate (88% vs. 80%, HR 0.62) (N. Engl. J. Med. 2012;366:1770-81).

Younger Group in IFM Trial

Dr. Michel Attal of Hôpital Purpan in Toulouse, France, and his colleagues from the Intergroupe Francophone du Myélome (IFM) conducted a similar trial in a population of 614 patients under age 65 whose disease had not progressed after stem cell transplantation. All patients received two 28-day cycles of consolidation treatment with lenalidomide (25 mg daily on days 121) followed by maintenance with placebo or lenalidomide (10 mg daily for 3 months, after which the dose could be increased to 15 mg if tolerated) until disease progression.

At the time the study was unblinded at a median follow-up of 30 months in July 2010, median progression-free survival was nearly twice as long with lenalidomide maintenance – 41 months, compared with 23 months with a placebo (HR, 0.50; P less than .001). Overall survival was similar between the groups, and neither group had reached median overall survival.

By October 2011, median follow-up from time of randomization had reached 45 months, and the probability of surviving without progression 4 years after randomization was still about double with lenalidomide: 43% vs. 22% (HR, 0.50; P less than .001).

The overall survival rate was still similar, however, at 73% with lenalidomide and 75% with placebo. These survival rates are high, the authors noted, and longer follow-up may show an advantage for lenalidomide maintenance.

"Together with the findings reported by McCarthy et al., our data support the use of lenalidomide maintenance therapy after high-dose chemotherapy and autologous hematopoietic stem-cell transplantation in patients with myeloma, but the impressive benefits must be weighed against the increased risks," said Dr. Attal and his coauthors (N. Engl. J. Med. 2012;366:1782-91).

Older Patients Ineligible for Transplant

Dr. Antonio Palumbo of the University of Turin, Italy, and his coinvestigators from the Multiple Myeloma-015 (MM-015) trial also explored continuous lenalidomide, but in a population of 459 patients aged 65 years and older who were not eligible for stem cell transplantation.

Patients were randomized to three groups: One group received induction therapy with melphalan, prednisone, and lenalidomide followed by lenalidomide maintenance (MPR-R); the second received MPR followed by placebo maintenance; and the third received only melphalan and prednisone (MP) followed by placebo. Investigators reported that about two-thirds of patients completed their induction regimens.

Median progression-free survival, the primary end point, was significantly longer in the group that received lenalidomide maintenance (31 months) than in the groups that received MPR with placebo (14 months) or MP without any lenalidomide in the induction and maintenance phases (13 months).

In a landmark analysis that looked at progression-free survival from the start of maintenance therapy, the median reached 26 months with lenalidomide vs. 7 months with placebo, with a hazard ratio of 0.34 for MPR-R vs. MPR (P less than .001).

Greater benefit was seen in patients 65-75 years of age, with median progression-free survival of 31 months with MPR-R, 15 months with MPR, and 12 months with MP. In patients over age 75, the medians were 19 months, 12 months, and 15 months, respectively.

Median overall survival at 3 years was not significantly different, reaching 70% with MPR-R, 62% with MPR, and 66% with MP.

"Altogether, these results confirm the benefits of maintenance therapy with respect to progression-free survival. The influence on overall survival remains unclear," concluded Dr. Palumbo and his coauthors (N. Engl. J. Med. 2012;366:1759-69).

Secondary Malignancies

In all three studies lenalidomide was associated with higher rates of secondary primary cancers.

• The rate was 8% in the lenalidomide group vs. 3% in the placebo group in the CALGB study.

• The IFM investigators calculated the incidence as 3.1 per 100 patient-years in their lenalidomide group vs. 1.2 per 100 patient-years with placebo (P = .002).

• In the MM-015 study, the 3-year rate was 7% with MPR-R, 7% with MPR, and 3% with MP. The increased risk was "mainly confined to acute myeloid leukemia or myelodysplastic syndromes, and is observed when lenalidomide is given with or after melphalan," the investigators wrote.

Other Adverse Events

Hematologic toxicity dominated the adverse event reports from all three studies.

• In the CALBG trial, grade 3 and 4 hematologic side effects were significantly more common with lenalidomide maintenance, as were grade 3 nonhematologic events. The most pronounced was neutropenia in 45% of the lenalidomide group vs. 15% of the placebo group (P less than .001).

• The IFM investigators also reported that grade 3 or 4 hematologic events were more frequent with lenalidomide than with placebo (58% vs. 23%, P less than .001), as were thromboembolic events (6% vs. 2%, P = .01).

• Similarly, the MM-015 group found that the most frequent adverse events were hematologic, with grade 4 neutropenia occurring in 35% of patients given lenalidomide. Nonhematologic events, including deep vein thrombosis, occurred at low rates, however, according to Dr. Palumbo and his coauthors. "Lenalidomide maintenance was associated with little evidence of cumulative toxic effects," they said.

How the safety profiles will influence adoption of lenalidomide maintenance is uncertain. "A major concern during maintenance therapy is toxicity that limits long-term use and the ability to receive future treatment after disease progression or that results in life-threatening disorders," noted Dr. McCarthy and his coauthors.

The National Cancer Institute supported the CALGB trial. Celgene, maker of lenalidomide, provided support for the IFM and MM-015 studies. The IFM trial also received support from the Programme Hospitalier de Recherche Clinique and the Swiss Group for Clinical Cancer Research (SAKK). Disclosure forms filed by individual investigators are posted at http://www.nejm.org.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A comparison of three radiotherapies for nonmetastatic prostate cancer supports the widespread use of intensity-modulated radiation treatment, though it leads to more erectile dysfunction than occurs with conformal radiation therapy, according to a report published April 17 in JAMA.

Proton therapy, the newest and most expensive option for these patients, fared poorly in the comparison. It had more GI side effects than intensity-modulated radiation treatment (IMRT) but was not more effective, investigators found.

Related Video >>

"Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer," wrote Dr. Nathan C. Sheets of the University of North Carolina, Chapel Hill, and his coauthors (JAMA 2012;307:1611-20).

Dr. Sheets presented the study in February at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

This study and another comparing external beam radiation therapy, prostatectomy, and brachytherapy provoked discussion of whether outcomes justified the costs of newer technologies.

IMRT, a more expensive, more targeted form of radiotherapy, has gradually replaced conformal radiation therapy (CRT), with its use surging from 0.15% in 2000 to 95.9% in 2008, according to Dr. Sheets and his coauthors. In turn, IMRT is facing increasing competition from proton therapy, which they describe as "a high-profile, high-cost prostate cancer treatment."

"Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," they observed, noting that comparative effectiveness research on these treatments is lacking.

To that end, the investigators used a propensity scoring method to analyze data on 12,976 men who were identified in the Surveillance, Epidemiology, and End Results program registry and had been treated between 2002 and 2006: 6,666 with IMRT and 6,310 with CRT.

The investigators found that men who received IMRT were about 20% less likely to receive additional cancer therapy, with an absolute risk of 2.5 vs. 3.1 per 100 person years (P less than .001).

The IMRT cohort also was significantly less likely to be diagnosed with GI morbidities (absolute risk, 13.4 vs. 14.7 per 100 person-years) and hip fractures (absolute risk, 0.8 vs. 1.0 per 100 person-years), but more likely to be diagnosed with erectile dysfunction than those who received CRT (absolute risk, 5.9 vs. 5.3 per 100 person-years).

In a smaller propensity-score matched comparison of 1,368 men treated with IMRT or proton therapy, the investigators found less GI morbidity with IMRT (absolute risk, 12.2 vs. 17.8 per 100 person-years) and no difference in efficacy.

"This population-based study suggests that IMRT may be associated with improved disease control without compromising morbidity compared with conformal radiation therapy, although proton therapy does not appear to provide additional benefit," they concluded.

The research was supported by the Agency for Healthcare Research and Quality. A grant from the National Institute of Nursing Research enabled publication. Two coauthors reported relationship with pharmaceutical companies.

A comparison of three radiotherapies for nonmetastatic prostate cancer supports the widespread use of intensity-modulated radiation treatment, though it leads to more erectile dysfunction than occurs with conformal radiation therapy, according to a report published April 17 in JAMA.

Proton therapy, the newest and most expensive option for these patients, fared poorly in the comparison. It had more GI side effects than intensity-modulated radiation treatment (IMRT) but was not more effective, investigators found.

Related Video >>

"Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer," wrote Dr. Nathan C. Sheets of the University of North Carolina, Chapel Hill, and his coauthors (JAMA 2012;307:1611-20).

Dr. Sheets presented the study in February at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

This study and another comparing external beam radiation therapy, prostatectomy, and brachytherapy provoked discussion of whether outcomes justified the costs of newer technologies.

IMRT, a more expensive, more targeted form of radiotherapy, has gradually replaced conformal radiation therapy (CRT), with its use surging from 0.15% in 2000 to 95.9% in 2008, according to Dr. Sheets and his coauthors. In turn, IMRT is facing increasing competition from proton therapy, which they describe as "a high-profile, high-cost prostate cancer treatment."

"Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," they observed, noting that comparative effectiveness research on these treatments is lacking.

To that end, the investigators used a propensity scoring method to analyze data on 12,976 men who were identified in the Surveillance, Epidemiology, and End Results program registry and had been treated between 2002 and 2006: 6,666 with IMRT and 6,310 with CRT.

The investigators found that men who received IMRT were about 20% less likely to receive additional cancer therapy, with an absolute risk of 2.5 vs. 3.1 per 100 person years (P less than .001).

The IMRT cohort also was significantly less likely to be diagnosed with GI morbidities (absolute risk, 13.4 vs. 14.7 per 100 person-years) and hip fractures (absolute risk, 0.8 vs. 1.0 per 100 person-years), but more likely to be diagnosed with erectile dysfunction than those who received CRT (absolute risk, 5.9 vs. 5.3 per 100 person-years).

In a smaller propensity-score matched comparison of 1,368 men treated with IMRT or proton therapy, the investigators found less GI morbidity with IMRT (absolute risk, 12.2 vs. 17.8 per 100 person-years) and no difference in efficacy.

"This population-based study suggests that IMRT may be associated with improved disease control without compromising morbidity compared with conformal radiation therapy, although proton therapy does not appear to provide additional benefit," they concluded.

The research was supported by the Agency for Healthcare Research and Quality. A grant from the National Institute of Nursing Research enabled publication. Two coauthors reported relationship with pharmaceutical companies.

A comparison of three radiotherapies for nonmetastatic prostate cancer supports the widespread use of intensity-modulated radiation treatment, though it leads to more erectile dysfunction than occurs with conformal radiation therapy, according to a report published April 17 in JAMA.

Proton therapy, the newest and most expensive option for these patients, fared poorly in the comparison. It had more GI side effects than intensity-modulated radiation treatment (IMRT) but was not more effective, investigators found.

Related Video >>

"Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer," wrote Dr. Nathan C. Sheets of the University of North Carolina, Chapel Hill, and his coauthors (JAMA 2012;307:1611-20).

Dr. Sheets presented the study in February at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

This study and another comparing external beam radiation therapy, prostatectomy, and brachytherapy provoked discussion of whether outcomes justified the costs of newer technologies.

IMRT, a more expensive, more targeted form of radiotherapy, has gradually replaced conformal radiation therapy (CRT), with its use surging from 0.15% in 2000 to 95.9% in 2008, according to Dr. Sheets and his coauthors. In turn, IMRT is facing increasing competition from proton therapy, which they describe as "a high-profile, high-cost prostate cancer treatment."

"Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," they observed, noting that comparative effectiveness research on these treatments is lacking.

To that end, the investigators used a propensity scoring method to analyze data on 12,976 men who were identified in the Surveillance, Epidemiology, and End Results program registry and had been treated between 2002 and 2006: 6,666 with IMRT and 6,310 with CRT.

The investigators found that men who received IMRT were about 20% less likely to receive additional cancer therapy, with an absolute risk of 2.5 vs. 3.1 per 100 person years (P less than .001).

The IMRT cohort also was significantly less likely to be diagnosed with GI morbidities (absolute risk, 13.4 vs. 14.7 per 100 person-years) and hip fractures (absolute risk, 0.8 vs. 1.0 per 100 person-years), but more likely to be diagnosed with erectile dysfunction than those who received CRT (absolute risk, 5.9 vs. 5.3 per 100 person-years).

In a smaller propensity-score matched comparison of 1,368 men treated with IMRT or proton therapy, the investigators found less GI morbidity with IMRT (absolute risk, 12.2 vs. 17.8 per 100 person-years) and no difference in efficacy.

"This population-based study suggests that IMRT may be associated with improved disease control without compromising morbidity compared with conformal radiation therapy, although proton therapy does not appear to provide additional benefit," they concluded.

The research was supported by the Agency for Healthcare Research and Quality. A grant from the National Institute of Nursing Research enabled publication. Two coauthors reported relationship with pharmaceutical companies.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.

The 2011 San Antonio Breast Cancer Symposium that opened Dec. 6 features a hefty number of studies that could change clinical practice in the treatment of breast cancer.

Oncologists have been eagerly awaiting data from the phase III BOLERO-2 and CLEOPATRA trials, which are to be presented Dec. 8 and 9, respectively.

– BOLERO-2 investigators reported that pairing everolimus (Afinitor) with exemestane (Aromasin) increased median progression-free survival by 4.1 months in an interim analysis presented this fall at the European Multidisciplinary Cancer Congress in Stockholm. Women in this study had estrogen receptor-positive disease that was resistant to hormone therapy.

– Genentech announced last summer that dual HER2 blockade with pertuzumab* and trastuzumab (Herceptin) improved progression-free survival for women with HER2-positive disease who also received docetaxel (Taxotere) in CLEOPATRA. The pairing has also produced good results in the NeoSphere trial, and early reports from studies pairing lapatinib (Tykerb) with trastuzumab have been encouraging.

On Dec. 7, an early-morning press briefing has been scheduled for investigators to outline findings of four noteworthy studies.

– Swedish researchers will report that diabetes and obesity after age 60 are risk factors for breast cancer. Low lipids also increased risk, but high lipids did not in their study comparing medical records of more than 23,000 women. Similarly, risk went up with use of the diabetes drug glargine but down with metformin.

– Gene expression patterns at diagnosis of hormone receptor–positive breast cancer can predict which women will have recurrences late, early, or not at all, according to researchers from the United States.

– Women treated with brachytherapy were about twice as likely to undergo subsequent mastectomy when compared with those treated by whole breast irradiation in a study of more than 150,000 Medicare claims.

– A ductal carcinoma in situ (DCIS) risk score based on the multigene Oncotype DX assay has been validated for prediction of breast cancer recurrence in DCIS patients.

Other Dec. 7 highlights will include presentations from four studies of bisphosphonate use in breast cancer patients and an Institute of Medicine report on "Breast Cancer and the Environment."

For ongoing coverage of these and other presentations at the San Antonio Breast Cancer Symposium, visit http://www.oncologyreport.com.

*Correction, Dec. 8, 2011: An earlier version of this story referred to pertuzumab by the trade name Omnitarg. That trade name was discontinued by Genentech in 2007 and currently the drug goes by pertuzumab.