Susan London

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

CHICAGO – A new approach to treating the axilla in women with early breast cancer has considerably less morbidity than the current approach, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In the randomized phase III trial – After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) – 1,425 women with early breast cancer were randomized roughly evenly to the current standard of surgical axillary lymph node dissection (ALND) or to axillary radiation therapy. Each participant had a positive sentinel node but clinically negative axillary nodes.

After 5 years of follow-up, the groups had a similarly low rates of cancer recurrence in the axilla of roughly 1%, Dr. Emiel J.T. Rutgers reported on behalf of his coinvestigators with the European Organisation for Research and Treatment of Cancer (EORTC). The radiation therapy group, however, was half as likely as the ALND group to develop lymphedema.

"The trial shows that, if treatment of the axillary lymph nodes in breast cancer is deemed necessary due to larger tumor size and sentinel lymph node involvement, radiotherapy to the axilla is a good alternative – maybe for us a better alternative – as compared to surgery because it’s associated with less side effects and has an extremely good regional cancer control," Dr. Rutgers commented in a press briefing.

The incidence of observed side effects in the radiation therapy group has been decreasing with time, and there is no reason to think that trend will reverse, said Dr. Rutgers, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam. Yet, as late effects can emerge over time, the patients will be followed up for at least another 5 years.

Even though they might perceive surgery to be more effective, women can be reassured that radiation therapy will be adequate treatment, for several reasons, he said. First, only a minority of women with a positive sentinel node actually have other affected nodes. Second, the effectiveness of radiation for local control has been established in the breast conservation setting.

The findings are part of a general trend toward less extensive treatment in breast cancer. "We have shifted from 20 or 30 years ago from mastectomy to breast conservation. And now we will shift from complete axillary treatment to axillary-conserving strategies," he noted.

"It’s really incredible how quickly it seems in the last few years we are rethinking the locoregional management of breast cancer, with less surgery, and perhaps now, maybe an increase for the role of radiotherapy for local control," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

He agreed that there is a growing philosophy of less is more in the sentinel-node era. "So I would certainly try to assure patients that we try to rely on high-level evidence-based medicine ... that you can do this safely," he said.

There has been increasing uptake of radiation therapy of the axilla in the Netherlands, although it is not yet the standard of care, according to Dr. Rutgers.

Whether it will become standard of care in the United States "will remain to be seen over the next few months when people have a chance to critically review and absorb the data that will be presented today," Dr. Seidman said. "I do expect it is going to change practice at my institution and widely. Extensive surgery in the axilla can be a particular problem for certain selected medical comorbidities, and I suspect at least initially, radiation therapy will be used selectively and thoughtfully based on these data."

The AMAROS trial was open to patients with early invasive breast cancer who had tumors up to 5 cm in diameter and clinically negative lymph nodes. Those with a positive sentinel node were randomized to ALND (n = 744) or axillary radiation therapy (n = 681).

The radiation therapy was to levels I, II, and III and the supraclavicular area. The investigators used contemporary techniques to minimize exposure of healthy tissue. "There was a heavy quality control program for radiotherapy to spare lung and nerves," Dr. Rutgers said.

In the ALND group, the median number of nodes removed was 15. Two-thirds of patients did not have any additional positive nodes, other than the sentinel node.

After a median follow-up of 6.1 years, the rate of axillary recurrence was "extremely low," Dr. Rutgers reported: 0.54% with ALND and 1.03% with axillary radiation therapy.

"The axillary recurrence rate was to me, happily enough, far below that hypothesized [during the trial’s planning]; hence, the trial was underpowered," he noted in the session where the findings were presented.

The groups were statistically indistinguishable in estimated 5-year rates of overall survival, at about 93%, and disease-free survival, at about 85%.

The 5-year rate of lymphedema – defined in the study as the need for treatment with a sleeve garment, compression therapy, or lymph drainage therapy, or presence of the condition on physical examination – was 28% with ALND and 14% with axillary radiation therapy (P less than .0001), according to Dr. Rutgers.

"The side effects of radiotherapy cannot be neglected but are limited," he commented. "We looked at many other potential side effects of radiotherapy. There was no excess of cardiac problems, a very small excess of radiation pneumonitis; there was no effect on the brachial nerves."

The groups did not differ with respect to overall quality of life, but there were trends toward greater difficulty moving the arm after radiation therapy and greater swelling after ALND.

Dr. Rutgers disclosed no conflicts of interest related to the research.

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – Weekly paclitaxel is just as efficacious as dose-dense paclitaxel when it comes to adjuvant chemotherapy for breast cancer, but the weekly schedule has lower rates of certain important toxicities, according to data presented at the annual meeting of the American Society of Clinical Oncology.

The Southwest Oncology Group’s S0221 randomized trial tested combination chemotherapy regimens among 3,294 patients who had completed local therapy for early breast cancer.

Half of the patients received lower-dose paclitaxel (Taxol) weekly for twelve cycles, while the other half received standard-dose paclitaxel every 2 weeks for six cycles according to a dose-dense schedule. The dose-dense schedule used in the trial was longer than the standard dose-dense schedule (six cycles vs. four cycles) so that the groups would be on treatment for the same total duration (12 weeks).

The 5-year rate of disease-free survival was equally high, about 80%, with each schedule, reported lead study author Dr. G. Thomas Budd, a medical oncologist at the Cleveland Clinic. The weekly schedule, however, yielded significantly lower rates of grade 3/4 musculoskeletal pain, allergy, and neurotoxicity.

"Either schedule of administration can be recommended based on efficacy, so in practice, treatment can be selected based on other considerations such as toxicity. ... It can be individualized by the patient and their physician," he said. "I think there will be a move to more weekly treatment since hematopoietic growth factor support is not required."

Treatment duration and frequency also might tip the decision one way or another for some patients, he added in a related press briefing, as patients given paclitaxel every 2 weeks with the current practice of four cycles will finish chemotherapy sooner, and patients on the weekly schedule will have to travel to the infusion center more often.

"I think that it’s remarkable that after two decades [since paclitaxel’s approval] we are still asking questions on how to teach an old dog new tricks, so to speak," commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

"For me, this is actually going to change my practice because I have generally given" paclitaxel every 2 weeks, he said. "These data suggest to me that I can get the same benefit with less toxicity [with the weekly schedule], possibly with less cost. Although there was no formal economic analysis, the cost of growth factor support is not trivial."

In addition, "there are patients for whom fine motor skills are very important to their livelihood, and they will be happy to hear this news" about less neurotoxicity with weekly scheduling, he said.

The S0221 trial enrolled patients with stage I-III breast cancer who had received adequate local therapy (resection and radiation therapy). Investigators randomized them twice with a factorial design.

The first randomization was for a doxorubicin and cyclophosphamide schedule – investigational (weekly) versus standard (every 2 weeks). This randomization was discontinued because the investigational schedule was not more efficacious; all patients thereafter received the standard schedule, according to Dr. Budd.

The second randomization was for the schedule of paclitaxel – either a lower-dose weekly schedule (80 mg/m² every week × 12 weeks) or a dose-dense schedule (175 mg/m² every 2 weeks × 6 weeks) – with granulocytecolony-stimulating factor (pegfilgrastim) support.

Efficacy results showed that the weekly and every-2-week schedules yielded statistically indistinguishable estimated 5-year disease-free survival (82% for the former and 81% for the latter).

"Since this was not conducted as a noninferiority study, we cannot make a conclusion about the lack of difference. However, the Kaplan-Meier curves and the computed hazard ratios suggest little difference in efficacy between these two arms," Dr. Budd commented.

There was also no significant difference between the paclitaxel schedules in overall survival; median values have not been reached.

The findings were generally similar in patient subgroups stratified according to tumor hormone receptor and HER2 status, and, within the HER2-positive group, according to receipt of trastuzumab (Herceptin).

There was no significant difference in the overall rate of grade 3/4 adverse events with the weekly versus every-2-week schedules (35% vs. 36%), but there were differences in rates of individual types of events.

The weekly schedule was associated with significantly lower rates of allergic reaction (0.6% vs. 1.4%), musculoskeletal pain (3% vs. 11%), and neurotoxicity (10% vs. 17%), although the difference in neurotoxicity may have been smaller had the patients in the dose-dense group received only four cycles of every-2-week paclitaxel (as is current practice) rather than six cycles, Dr. Budd acknowledged.

On the flip side, the weekly schedule was associated with significantly higher rates of grade 3/4 hematologic toxicity (17% vs. 6%), leukopenia (6% vs. 1%), and neutropenia (11% vs. 2%). It’s important to remember, however, that "these patients had their counts checked more frequently, they did not receive hematopoietic growth factors, and the rates of infectious complications were not different between the two arms," he said.

The investigators have not performed a formal pharmacoeconomic analysis, according to Dr. Budd, but "the weekly schedule is somewhere between a third and two-thirds less expensive, just on the basis of calculating drug costs."

Dr. Budd disclosed that he is a consultant to Amgen, maker of pegfilgrastim (Neulasta).

CHICAGO – Adding the antiangiogenic agent bevacizumab to chemotherapy improves overall survival in women who have advanced cervical cancer, according to findings of a randomized phase III trial of the Gynecologic Oncology Group.

In the trial – Gynecologic Oncology Group (GOG) protocol 240 – women who received bevacizumab (Avastin) in addition to chemotherapy lived about 4 months longer than their counterparts who received chemotherapy alone, lead investigator Dr. Krishnansu S. Tewari reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

The adverse effects seen were largely consistent with previous experience in other cancers with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor.

"This study met its primary endpoint," said Dr. Tewari, a professor of obstetrics and gynecology at the University of California, Irvine. "Bevacizumab is the first molecularly targeted agent to improve overall survival in a gynecologic cancer."

"Moving forward, the incorporation of anti-VEGF therapy into primary treatment for locally advanced disease should be considered ..." he said. Also, "these data open up doors to study other classes of antiangiogenesis agents – both VEGF-dependent molecules as well as non–VEGF-dependent molecules."

Invited discussant Dr. Gottfried E. Konecny of the University of California, Los Angeles, commented, "Progression-free and overall survival improvements through bevacizumab in advanced cervical cancer as shown in the GOG 240 study are clinically meaningful. Adverse events and toxicities are manageable and, I believe, class specific."

In his opinion, as only about a fifth of the patients had metastatic disease, it is uncertain whether the drug benefits that population. And the data suggest bevacizumab may have less benefit in patients with adenocarcinoma tumors as compared with squamous tumors.

For future research, "most important is the identification and validation of response predictors," according to Dr. Konecny.

"Extending the global reach of antiangiogenic therapies for advanced cervical cancer is critical," he concluded, noting that the countries with highest incidence and mortality rates for this disease also have the lowest annual health care spending. "I think GOG 240 can be seen as a practice-changing study. But we urgently need to develop antiangiogenic treatment strategies that will benefit the global population."

The trial was open to women who had chemotherapy-naive, recurrent, persistent, or metastatic cervical cancer. They were randomized in dual factorial design according to chemotherapy doublet (cisplatin plus paclitaxel vs. topotecan plus paclitaxel) and receipt of bevacizumab (yes vs. no), which was provided by Roche/Genentech, manufacturer of the recombinant monoclonal antibody. Treatment was on an open-label basis, and crossover was not allowed.

Bevacizumab is approved by the Food and Drug Administration for selected indications in colorectal, renal, and lung cancer, and in glioblastoma.

An interim analysis concluded that the topotecan-paclitaxel regimen was not superior (or inferior) to the cisplatin-paclitaxel regimen that has been the standard in this setting, Dr. Tewari reported.

With longer follow-up, to a median of 20.8 months, women who received added bevacizumab had a longer median overall survival than did their counterparts who received chemotherapy alone (17.0 vs. 13.3 months; hazard ratio, 0.71; P = .0035).

Bevacizumab conferred a significant survival benefit when added to cisplatin-paclitaxel chemotherapy (HR, 0.68; P = .03) but not when added to topotecan-paclitaxel chemotherapy (HR, 0.74; P = .09).

"The effect of bevacizumab was sustained with multiple prognostic factors, including when the disease was in the previously irradiated pelvis," Dr. Tewari noted when reporting subgroup analyses.

Women who received added bevacizumab also had a longer median progression-free survival (8.2 vs. 5.9 months; HR, 0.67; P = .0002) and a higher response rate (48% vs. 36%, P = .008).

Adding bevacizumab led to significantly higher rates of grade 3/4 gastrointestinal fistula (3% vs. 0%), genitourinary fistula (2% vs. 0%), and thromboembolism (8% vs. 1%); grade 2 or higher hypertension (25% vs. 2%); and grade 4 or higher neutropenia (35% vs. 26%).

"We saw no new adverse events in this patient population, which includes patients who had been heavily irradiated," Dr. Tewari commented. There were four deaths each in the groups treated with and without bevacizumab.

Addition of bevacizumab did not compromise health-related quality of life as assessed with the FACT(Functional Assessment of Cancer Therapy) – Cervical Cancer Trial Outcome Index.

Dr. Tewari disclosed no relevant conflicts of interest. Dr. Konecny disclosed that he receives honoraria from Genentech and Sanofi, and research funding from Amgen and Pfizer.

CHICAGO – Adding the antiangiogenic agent bevacizumab to chemotherapy improves overall survival in women who have advanced cervical cancer, according to findings of a randomized phase III trial of the Gynecologic Oncology Group.

In the trial – Gynecologic Oncology Group (GOG) protocol 240 – women who received bevacizumab (Avastin) in addition to chemotherapy lived about 4 months longer than their counterparts who received chemotherapy alone, lead investigator Dr. Krishnansu S. Tewari reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

The adverse effects seen were largely consistent with previous experience in other cancers with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor.

"This study met its primary endpoint," said Dr. Tewari, a professor of obstetrics and gynecology at the University of California, Irvine. "Bevacizumab is the first molecularly targeted agent to improve overall survival in a gynecologic cancer."

"Moving forward, the incorporation of anti-VEGF therapy into primary treatment for locally advanced disease should be considered ..." he said. Also, "these data open up doors to study other classes of antiangiogenesis agents – both VEGF-dependent molecules as well as non–VEGF-dependent molecules."

Invited discussant Dr. Gottfried E. Konecny of the University of California, Los Angeles, commented, "Progression-free and overall survival improvements through bevacizumab in advanced cervical cancer as shown in the GOG 240 study are clinically meaningful. Adverse events and toxicities are manageable and, I believe, class specific."

In his opinion, as only about a fifth of the patients had metastatic disease, it is uncertain whether the drug benefits that population. And the data suggest bevacizumab may have less benefit in patients with adenocarcinoma tumors as compared with squamous tumors.

For future research, "most important is the identification and validation of response predictors," according to Dr. Konecny.

"Extending the global reach of antiangiogenic therapies for advanced cervical cancer is critical," he concluded, noting that the countries with highest incidence and mortality rates for this disease also have the lowest annual health care spending. "I think GOG 240 can be seen as a practice-changing study. But we urgently need to develop antiangiogenic treatment strategies that will benefit the global population."

The trial was open to women who had chemotherapy-naive, recurrent, persistent, or metastatic cervical cancer. They were randomized in dual factorial design according to chemotherapy doublet (cisplatin plus paclitaxel vs. topotecan plus paclitaxel) and receipt of bevacizumab (yes vs. no), which was provided by Roche/Genentech, manufacturer of the recombinant monoclonal antibody. Treatment was on an open-label basis, and crossover was not allowed.

Bevacizumab is approved by the Food and Drug Administration for selected indications in colorectal, renal, and lung cancer, and in glioblastoma.

An interim analysis concluded that the topotecan-paclitaxel regimen was not superior (or inferior) to the cisplatin-paclitaxel regimen that has been the standard in this setting, Dr. Tewari reported.

With longer follow-up, to a median of 20.8 months, women who received added bevacizumab had a longer median overall survival than did their counterparts who received chemotherapy alone (17.0 vs. 13.3 months; hazard ratio, 0.71; P = .0035).

Bevacizumab conferred a significant survival benefit when added to cisplatin-paclitaxel chemotherapy (HR, 0.68; P = .03) but not when added to topotecan-paclitaxel chemotherapy (HR, 0.74; P = .09).

"The effect of bevacizumab was sustained with multiple prognostic factors, including when the disease was in the previously irradiated pelvis," Dr. Tewari noted when reporting subgroup analyses.

Women who received added bevacizumab also had a longer median progression-free survival (8.2 vs. 5.9 months; HR, 0.67; P = .0002) and a higher response rate (48% vs. 36%, P = .008).

Adding bevacizumab led to significantly higher rates of grade 3/4 gastrointestinal fistula (3% vs. 0%), genitourinary fistula (2% vs. 0%), and thromboembolism (8% vs. 1%); grade 2 or higher hypertension (25% vs. 2%); and grade 4 or higher neutropenia (35% vs. 26%).

"We saw no new adverse events in this patient population, which includes patients who had been heavily irradiated," Dr. Tewari commented. There were four deaths each in the groups treated with and without bevacizumab.

Addition of bevacizumab did not compromise health-related quality of life as assessed with the FACT(Functional Assessment of Cancer Therapy) – Cervical Cancer Trial Outcome Index.

Dr. Tewari disclosed no relevant conflicts of interest. Dr. Konecny disclosed that he receives honoraria from Genentech and Sanofi, and research funding from Amgen and Pfizer.

CHICAGO – Adding the antiangiogenic agent bevacizumab to chemotherapy improves overall survival in women who have advanced cervical cancer, according to findings of a randomized phase III trial of the Gynecologic Oncology Group.

In the trial – Gynecologic Oncology Group (GOG) protocol 240 – women who received bevacizumab (Avastin) in addition to chemotherapy lived about 4 months longer than their counterparts who received chemotherapy alone, lead investigator Dr. Krishnansu S. Tewari reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.

The adverse effects seen were largely consistent with previous experience in other cancers with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor.

"This study met its primary endpoint," said Dr. Tewari, a professor of obstetrics and gynecology at the University of California, Irvine. "Bevacizumab is the first molecularly targeted agent to improve overall survival in a gynecologic cancer."

"Moving forward, the incorporation of anti-VEGF therapy into primary treatment for locally advanced disease should be considered ..." he said. Also, "these data open up doors to study other classes of antiangiogenesis agents – both VEGF-dependent molecules as well as non–VEGF-dependent molecules."

Invited discussant Dr. Gottfried E. Konecny of the University of California, Los Angeles, commented, "Progression-free and overall survival improvements through bevacizumab in advanced cervical cancer as shown in the GOG 240 study are clinically meaningful. Adverse events and toxicities are manageable and, I believe, class specific."

In his opinion, as only about a fifth of the patients had metastatic disease, it is uncertain whether the drug benefits that population. And the data suggest bevacizumab may have less benefit in patients with adenocarcinoma tumors as compared with squamous tumors.

For future research, "most important is the identification and validation of response predictors," according to Dr. Konecny.

"Extending the global reach of antiangiogenic therapies for advanced cervical cancer is critical," he concluded, noting that the countries with highest incidence and mortality rates for this disease also have the lowest annual health care spending. "I think GOG 240 can be seen as a practice-changing study. But we urgently need to develop antiangiogenic treatment strategies that will benefit the global population."

The trial was open to women who had chemotherapy-naive, recurrent, persistent, or metastatic cervical cancer. They were randomized in dual factorial design according to chemotherapy doublet (cisplatin plus paclitaxel vs. topotecan plus paclitaxel) and receipt of bevacizumab (yes vs. no), which was provided by Roche/Genentech, manufacturer of the recombinant monoclonal antibody. Treatment was on an open-label basis, and crossover was not allowed.

Bevacizumab is approved by the Food and Drug Administration for selected indications in colorectal, renal, and lung cancer, and in glioblastoma.

An interim analysis concluded that the topotecan-paclitaxel regimen was not superior (or inferior) to the cisplatin-paclitaxel regimen that has been the standard in this setting, Dr. Tewari reported.

With longer follow-up, to a median of 20.8 months, women who received added bevacizumab had a longer median overall survival than did their counterparts who received chemotherapy alone (17.0 vs. 13.3 months; hazard ratio, 0.71; P = .0035).

Bevacizumab conferred a significant survival benefit when added to cisplatin-paclitaxel chemotherapy (HR, 0.68; P = .03) but not when added to topotecan-paclitaxel chemotherapy (HR, 0.74; P = .09).

"The effect of bevacizumab was sustained with multiple prognostic factors, including when the disease was in the previously irradiated pelvis," Dr. Tewari noted when reporting subgroup analyses.

Women who received added bevacizumab also had a longer median progression-free survival (8.2 vs. 5.9 months; HR, 0.67; P = .0002) and a higher response rate (48% vs. 36%, P = .008).

Adding bevacizumab led to significantly higher rates of grade 3/4 gastrointestinal fistula (3% vs. 0%), genitourinary fistula (2% vs. 0%), and thromboembolism (8% vs. 1%); grade 2 or higher hypertension (25% vs. 2%); and grade 4 or higher neutropenia (35% vs. 26%).

"We saw no new adverse events in this patient population, which includes patients who had been heavily irradiated," Dr. Tewari commented. There were four deaths each in the groups treated with and without bevacizumab.

Addition of bevacizumab did not compromise health-related quality of life as assessed with the FACT(Functional Assessment of Cancer Therapy) – Cervical Cancer Trial Outcome Index.

Dr. Tewari disclosed no relevant conflicts of interest. Dr. Konecny disclosed that he receives honoraria from Genentech and Sanofi, and research funding from Amgen and Pfizer.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Dr. G. T. Budd, of the Cleveland Clinic, discusses the efficacy, side effects, and costs of giving paclitaxel weekly vs. every 2 weeks when treating breast cancer. Dr. Budd discussed trial results comparing the schedules in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Bevacizumab plus chemotherapy may extend the lives of women with recurrent metastatic cervical cancer, according to new study results presented at the American Society of Clinical Oncology. Compared with patients treated with chemotherapy alone, patients treated with chemotherapy plus bevacizumab had an improved median overall survival.

Dr. Krishnansu Tewari, who believes bevacizumab will be practice changing, presented the trial results at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Bevacizumab plus chemotherapy may extend the lives of women with recurrent metastatic cervical cancer, according to new study results presented at the American Society of Clinical Oncology. Compared with patients treated with chemotherapy alone, patients treated with chemotherapy plus bevacizumab had an improved median overall survival.

Dr. Krishnansu Tewari, who believes bevacizumab will be practice changing, presented the trial results at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Bevacizumab plus chemotherapy may extend the lives of women with recurrent metastatic cervical cancer, according to new study results presented at the American Society of Clinical Oncology. Compared with patients treated with chemotherapy alone, patients treated with chemotherapy plus bevacizumab had an improved median overall survival.

Dr. Krishnansu Tewari, who believes bevacizumab will be practice changing, presented the trial results at the annual meeting of the American Society of Clinical Oncology.

CHICAGO — A simple approach to cervical cancer screening that can be easily implemented in resource-strapped settings could save tens of thousands of lives worldwide each year, researchers reported at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Surendra Srinivas Shastri, a professor of preventive oncology at Tata Memorial Center in Mumbai, India, conducted a cluster-randomized trial of visual inspection with acetic acid (VIA) among more than 150,000 women living in some of India’s poorest areas.

Main results showed that women who had four rounds of biennial screening with VIA delivered by trained health workers were almost a third less likely to die from cervical cancer than peers who were not screened, which is usual care in India given the lack of infrastructure and resources for country-wide Pap screening.

Susan London/IMNG Medical Media

Of note, the health workers were women, who were drawn mainly from the local community and who had a 10th grade education, according Dr. Shastri. Such professionals can reach remote and rural areas of the country, he said. Additionally, the VIA technique does not require a laboratory and provides immediate results.

"It is widely implementable in the lowest-resource settings in India or wherever," he said in a press briefing. "If implemented nationally in India, it would prevent around 22,000 cervical cancer deaths in the country. And if taken globally in middle-income and low-resource countries, we could prevent around 72,000 deaths in developing countries annually."

On the basis of the trial’s results, India is preparing to implement the VIA program nationally. He said that training of health workers, using a train-the-trainers approach, and a quality control process could be completed within 6 months.

Women receiving a cancer diagnosis through the VIA program will have access to treatment, assured Dr. Rajendra A. Badwe, one of the trial’s co-investigators and director of the Tata Memorial Center.

"There is a cafeteria choice" in India, he explained. "Individuals can have free treatment, individuals can pay for treatment. And treatment is currently available in 34 regional cancer centers run by the government of India. The way I see it, for any screening trial, if there is something done [to identify cancer], we need to be proactively with them to see that they reach the closest treatment facility... [Treatment] will be made available – no question."

The trial has established that VIA is "a good alternative" to Pap screening in limited-resource settings, according to Electra D. Paskett, Ph.D., co-program leader of the Cancer Control Program in the Comprehensive Cancer Center at the Ohio State University in Columbus and an ASCO spokesperson. And there may well be a role for VIA screening in some settings in developed countries.

"From my perspective, it could be an alternative ... in more resource-rich countries where there are these pockets of high cervical cancer incidence and mortality that don’t have access to the same treatment resources that the rest of the country does," she said in the press briefing. "And we do have those pockets here in the United States."

The trial was conducted in 20 impoverished areas of Mumbai that were assigned evenly to VIA screening and control groups. The target population was women aged 35 to 64 years who had no prior history of cancer.

Women in both groups received cancer education. In the VIA group, women underwent four rounds of biennial screening; those with positive results were referred to a health facility for definitive diagnosis. In the control group, women were asked to report to the health workers any signs or symptoms of cervical cancer; those doing so were similarly referred to a health facility. All women receiving a cancer diagnosis were offered free treatment.

Analyses were based on 75,360 women in the VIA screening group and 76,178 women in the control group.

"The screening participation rate was 89% – huge for a country like India and most other cases," Dr. Shastri commented. Participation in education in the control group was also high, at 91%. Overall, 86% of women with a confirmed case of cervical cancer received treatment.

The screening and control groups did not differ significantly with respect to the incidence of invasive cervical cancer (26.7 vs. 27.5 per 100,000), suggesting that screening did not lead to overdiagnosis.

"Overdiagnosis is a huge problem in all screening programs and all screening trials," Dr. Shastri noted. "There was almost zero overdiagnosis in this trial. In fact, what little overdiagnosis we had, that ceased by the eighth year."

In intention-to-treat analysis, screening with VIA resulted in a 31% reduction in the cervical cancer–specific death rates (11.1 vs. 16.2 deaths per 100,000; mortality rate ratio, 0.69, P = .003).

Screened women also had a 7% reduction in overall mortality stemming from earlier diagnosis, although this difference was not statistically significant.

Dr. Shastri disclosed no relevant conflicts of interest. Dr. Badwe disclosed no relevant conflicts of interest.

CHICAGO — A simple approach to cervical cancer screening that can be easily implemented in resource-strapped settings could save tens of thousands of lives worldwide each year, researchers reported at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Surendra Srinivas Shastri, a professor of preventive oncology at Tata Memorial Center in Mumbai, India, conducted a cluster-randomized trial of visual inspection with acetic acid (VIA) among more than 150,000 women living in some of India’s poorest areas.

Main results showed that women who had four rounds of biennial screening with VIA delivered by trained health workers were almost a third less likely to die from cervical cancer than peers who were not screened, which is usual care in India given the lack of infrastructure and resources for country-wide Pap screening.

Susan London/IMNG Medical Media

Of note, the health workers were women, who were drawn mainly from the local community and who had a 10th grade education, according Dr. Shastri. Such professionals can reach remote and rural areas of the country, he said. Additionally, the VIA technique does not require a laboratory and provides immediate results.

"It is widely implementable in the lowest-resource settings in India or wherever," he said in a press briefing. "If implemented nationally in India, it would prevent around 22,000 cervical cancer deaths in the country. And if taken globally in middle-income and low-resource countries, we could prevent around 72,000 deaths in developing countries annually."

On the basis of the trial’s results, India is preparing to implement the VIA program nationally. He said that training of health workers, using a train-the-trainers approach, and a quality control process could be completed within 6 months.

Women receiving a cancer diagnosis through the VIA program will have access to treatment, assured Dr. Rajendra A. Badwe, one of the trial’s co-investigators and director of the Tata Memorial Center.

"There is a cafeteria choice" in India, he explained. "Individuals can have free treatment, individuals can pay for treatment. And treatment is currently available in 34 regional cancer centers run by the government of India. The way I see it, for any screening trial, if there is something done [to identify cancer], we need to be proactively with them to see that they reach the closest treatment facility... [Treatment] will be made available – no question."

The trial has established that VIA is "a good alternative" to Pap screening in limited-resource settings, according to Electra D. Paskett, Ph.D., co-program leader of the Cancer Control Program in the Comprehensive Cancer Center at the Ohio State University in Columbus and an ASCO spokesperson. And there may well be a role for VIA screening in some settings in developed countries.

"From my perspective, it could be an alternative ... in more resource-rich countries where there are these pockets of high cervical cancer incidence and mortality that don’t have access to the same treatment resources that the rest of the country does," she said in the press briefing. "And we do have those pockets here in the United States."

The trial was conducted in 20 impoverished areas of Mumbai that were assigned evenly to VIA screening and control groups. The target population was women aged 35 to 64 years who had no prior history of cancer.

Women in both groups received cancer education. In the VIA group, women underwent four rounds of biennial screening; those with positive results were referred to a health facility for definitive diagnosis. In the control group, women were asked to report to the health workers any signs or symptoms of cervical cancer; those doing so were similarly referred to a health facility. All women receiving a cancer diagnosis were offered free treatment.

Analyses were based on 75,360 women in the VIA screening group and 76,178 women in the control group.

"The screening participation rate was 89% – huge for a country like India and most other cases," Dr. Shastri commented. Participation in education in the control group was also high, at 91%. Overall, 86% of women with a confirmed case of cervical cancer received treatment.

The screening and control groups did not differ significantly with respect to the incidence of invasive cervical cancer (26.7 vs. 27.5 per 100,000), suggesting that screening did not lead to overdiagnosis.

"Overdiagnosis is a huge problem in all screening programs and all screening trials," Dr. Shastri noted. "There was almost zero overdiagnosis in this trial. In fact, what little overdiagnosis we had, that ceased by the eighth year."

In intention-to-treat analysis, screening with VIA resulted in a 31% reduction in the cervical cancer–specific death rates (11.1 vs. 16.2 deaths per 100,000; mortality rate ratio, 0.69, P = .003).

Screened women also had a 7% reduction in overall mortality stemming from earlier diagnosis, although this difference was not statistically significant.

Dr. Shastri disclosed no relevant conflicts of interest. Dr. Badwe disclosed no relevant conflicts of interest.

CHICAGO — A simple approach to cervical cancer screening that can be easily implemented in resource-strapped settings could save tens of thousands of lives worldwide each year, researchers reported at the annual meeting of the American Society of Clinical Oncology.

A team led by Dr. Surendra Srinivas Shastri, a professor of preventive oncology at Tata Memorial Center in Mumbai, India, conducted a cluster-randomized trial of visual inspection with acetic acid (VIA) among more than 150,000 women living in some of India’s poorest areas.

Main results showed that women who had four rounds of biennial screening with VIA delivered by trained health workers were almost a third less likely to die from cervical cancer than peers who were not screened, which is usual care in India given the lack of infrastructure and resources for country-wide Pap screening.

Susan London/IMNG Medical Media

Of note, the health workers were women, who were drawn mainly from the local community and who had a 10th grade education, according Dr. Shastri. Such professionals can reach remote and rural areas of the country, he said. Additionally, the VIA technique does not require a laboratory and provides immediate results.

"It is widely implementable in the lowest-resource settings in India or wherever," he said in a press briefing. "If implemented nationally in India, it would prevent around 22,000 cervical cancer deaths in the country. And if taken globally in middle-income and low-resource countries, we could prevent around 72,000 deaths in developing countries annually."

On the basis of the trial’s results, India is preparing to implement the VIA program nationally. He said that training of health workers, using a train-the-trainers approach, and a quality control process could be completed within 6 months.

Women receiving a cancer diagnosis through the VIA program will have access to treatment, assured Dr. Rajendra A. Badwe, one of the trial’s co-investigators and director of the Tata Memorial Center.

"There is a cafeteria choice" in India, he explained. "Individuals can have free treatment, individuals can pay for treatment. And treatment is currently available in 34 regional cancer centers run by the government of India. The way I see it, for any screening trial, if there is something done [to identify cancer], we need to be proactively with them to see that they reach the closest treatment facility... [Treatment] will be made available – no question."

The trial has established that VIA is "a good alternative" to Pap screening in limited-resource settings, according to Electra D. Paskett, Ph.D., co-program leader of the Cancer Control Program in the Comprehensive Cancer Center at the Ohio State University in Columbus and an ASCO spokesperson. And there may well be a role for VIA screening in some settings in developed countries.

"From my perspective, it could be an alternative ... in more resource-rich countries where there are these pockets of high cervical cancer incidence and mortality that don’t have access to the same treatment resources that the rest of the country does," she said in the press briefing. "And we do have those pockets here in the United States."

The trial was conducted in 20 impoverished areas of Mumbai that were assigned evenly to VIA screening and control groups. The target population was women aged 35 to 64 years who had no prior history of cancer.

Women in both groups received cancer education. In the VIA group, women underwent four rounds of biennial screening; those with positive results were referred to a health facility for definitive diagnosis. In the control group, women were asked to report to the health workers any signs or symptoms of cervical cancer; those doing so were similarly referred to a health facility. All women receiving a cancer diagnosis were offered free treatment.

Analyses were based on 75,360 women in the VIA screening group and 76,178 women in the control group.

"The screening participation rate was 89% – huge for a country like India and most other cases," Dr. Shastri commented. Participation in education in the control group was also high, at 91%. Overall, 86% of women with a confirmed case of cervical cancer received treatment.

The screening and control groups did not differ significantly with respect to the incidence of invasive cervical cancer (26.7 vs. 27.5 per 100,000), suggesting that screening did not lead to overdiagnosis.

"Overdiagnosis is a huge problem in all screening programs and all screening trials," Dr. Shastri noted. "There was almost zero overdiagnosis in this trial. In fact, what little overdiagnosis we had, that ceased by the eighth year."

In intention-to-treat analysis, screening with VIA resulted in a 31% reduction in the cervical cancer–specific death rates (11.1 vs. 16.2 deaths per 100,000; mortality rate ratio, 0.69, P = .003).

Screened women also had a 7% reduction in overall mortality stemming from earlier diagnosis, although this difference was not statistically significant.

Dr. Shastri disclosed no relevant conflicts of interest. Dr. Badwe disclosed no relevant conflicts of interest.

CHICAGO – The oral tyrosine kinase inhibitor pazopanib is likely to become a new option in maintenance therapy for advanced ovarian cancer, based on phase III trial results presented at the annual meeting of the American Society of Clinical Oncology.

Among the 940 patients studied, none of whom had disease progression after completing first-line chemotherapy, pazopanib (Votrient) prolonged median progression-free survival by 5.6 months as compared with placebo, reported lead author Dr. Andreas Du Bois, a professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany.

IMNG Medical Media

Pazopanib’s safety and tolerability profiles were as expected from previous experience with the drug and its known antiangiogenic activity, consisting mainly of adverse effects such as hypertension, diarrhea, and fatigue.

"Pazopanib maintenance therapy significantly extends time without recurrence and thus increases progression-free survival and delays need for further chemotherapy in ovarian cancer. So it prolongs the time the patient has control over the disease instead of disease having control over the patient," Dr. Du Bois commented in a press briefing.

"This is the first phase III maintenance study demonstrating superior outcome for a targeted therapy in ovarian cancer. Therefore, pazopanib may be a valuable option in the future" for this patient population, he added. "This study will be used for registration purposes, and hopefully we will have this drug available soon."

Dr. Du Bois acknowledged that previous trials have assessed use of bevacizumab (Avastin), another agent having antiangiogenic activity, for maintenance therapy. But bevacizumab was started together with chemotherapy and then continued. "It was not a pure maintenance setting," he said, so it is unclear which component was responsible for benefit.

Additionally, the trial populations differed in residual tumor burden, with 85% of the patients in the pazopanib trial having no evidence of residual disease at the time of enrollment.

Commenting during the press briefing, Dr. Carol Aghajanian, chief of the Gynecologic Medical Oncology Service at the Memorial Sloan-Kettering Cancer Center in New York and an ASCO spokesperson, said that the jury is still out on the optimal targeted agent and the optimal timing of its use in ovarian cancer.

"There has been a lot of discussion in ovarian cancer as to whether the patient should receive these agents as part of their initial treatment, or should you save this benefit for a later time in the course of their disease, at the time of treatment for recurrence or even at the time of treatment for platinum-resistant disease," she said. "But what we do have from the trial presented here by Dr. Du Bois is confirmation that targeting angiogenesis in ovarian cancer is important and effective."

Patients were eligible for the trail, the international intergroup trial AGO-OVAR16 sponsored by GlaxoSmithKline, if they had FIGO stage II to IV ovarian, fallopian tube, or primary peritoneal cancer, had not had progression after resection and completion of at least five cycles of first-line platinum-taxane chemotherapy, and had residual tumors measuring less than 2 cm.

They were randomized evenly to receive 800 mg pazopanib or placebo daily for 24 months.

Pazopanib is a multitargeted tyrosine kinase inhibitor that acts mainly on vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and c-kit signaling. It is approved by the Food and Drug Administration for treatment of kidney cancer and soft tissue sarcoma.

Main trial results showed that after a median follow-up of 24.3 months, median progression-free survival was 17.9 months with pazopanib and 12.3 months with placebo (hazard ratio, 0.77, P = .002). The findings were similar in subgroup analyses, according to Dr. Du Bois, who disclosed that he receives honoraria and research funding from GlaxoSmithKline.

An interim analysis of overall survival showed no significant difference between groups, but only a fifth of the patients had died as of the analysis.

Relative to placebo, pazopanib was associated with a higher incidence of serious adverse events (26% vs. 11%), according to the abstract. Three patients in the pazopanib group and one patient in the placebo group had a fatal serious adverse event.

"Predicting tolerability will be subject to further research," Dr. Du Bois noted.

CHICAGO – The oral tyrosine kinase inhibitor pazopanib is likely to become a new option in maintenance therapy for advanced ovarian cancer, based on phase III trial results presented at the annual meeting of the American Society of Clinical Oncology.

Among the 940 patients studied, none of whom had disease progression after completing first-line chemotherapy, pazopanib (Votrient) prolonged median progression-free survival by 5.6 months as compared with placebo, reported lead author Dr. Andreas Du Bois, a professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany.

IMNG Medical Media

Pazopanib’s safety and tolerability profiles were as expected from previous experience with the drug and its known antiangiogenic activity, consisting mainly of adverse effects such as hypertension, diarrhea, and fatigue.

"Pazopanib maintenance therapy significantly extends time without recurrence and thus increases progression-free survival and delays need for further chemotherapy in ovarian cancer. So it prolongs the time the patient has control over the disease instead of disease having control over the patient," Dr. Du Bois commented in a press briefing.

"This is the first phase III maintenance study demonstrating superior outcome for a targeted therapy in ovarian cancer. Therefore, pazopanib may be a valuable option in the future" for this patient population, he added. "This study will be used for registration purposes, and hopefully we will have this drug available soon."

Dr. Du Bois acknowledged that previous trials have assessed use of bevacizumab (Avastin), another agent having antiangiogenic activity, for maintenance therapy. But bevacizumab was started together with chemotherapy and then continued. "It was not a pure maintenance setting," he said, so it is unclear which component was responsible for benefit.

Additionally, the trial populations differed in residual tumor burden, with 85% of the patients in the pazopanib trial having no evidence of residual disease at the time of enrollment.

Commenting during the press briefing, Dr. Carol Aghajanian, chief of the Gynecologic Medical Oncology Service at the Memorial Sloan-Kettering Cancer Center in New York and an ASCO spokesperson, said that the jury is still out on the optimal targeted agent and the optimal timing of its use in ovarian cancer.

"There has been a lot of discussion in ovarian cancer as to whether the patient should receive these agents as part of their initial treatment, or should you save this benefit for a later time in the course of their disease, at the time of treatment for recurrence or even at the time of treatment for platinum-resistant disease," she said. "But what we do have from the trial presented here by Dr. Du Bois is confirmation that targeting angiogenesis in ovarian cancer is important and effective."

Patients were eligible for the trail, the international intergroup trial AGO-OVAR16 sponsored by GlaxoSmithKline, if they had FIGO stage II to IV ovarian, fallopian tube, or primary peritoneal cancer, had not had progression after resection and completion of at least five cycles of first-line platinum-taxane chemotherapy, and had residual tumors measuring less than 2 cm.

They were randomized evenly to receive 800 mg pazopanib or placebo daily for 24 months.

Pazopanib is a multitargeted tyrosine kinase inhibitor that acts mainly on vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and c-kit signaling. It is approved by the Food and Drug Administration for treatment of kidney cancer and soft tissue sarcoma.

Main trial results showed that after a median follow-up of 24.3 months, median progression-free survival was 17.9 months with pazopanib and 12.3 months with placebo (hazard ratio, 0.77, P = .002). The findings were similar in subgroup analyses, according to Dr. Du Bois, who disclosed that he receives honoraria and research funding from GlaxoSmithKline.

An interim analysis of overall survival showed no significant difference between groups, but only a fifth of the patients had died as of the analysis.

Relative to placebo, pazopanib was associated with a higher incidence of serious adverse events (26% vs. 11%), according to the abstract. Three patients in the pazopanib group and one patient in the placebo group had a fatal serious adverse event.

"Predicting tolerability will be subject to further research," Dr. Du Bois noted.

CHICAGO – The oral tyrosine kinase inhibitor pazopanib is likely to become a new option in maintenance therapy for advanced ovarian cancer, based on phase III trial results presented at the annual meeting of the American Society of Clinical Oncology.

Among the 940 patients studied, none of whom had disease progression after completing first-line chemotherapy, pazopanib (Votrient) prolonged median progression-free survival by 5.6 months as compared with placebo, reported lead author Dr. Andreas Du Bois, a professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany.

IMNG Medical Media

Pazopanib’s safety and tolerability profiles were as expected from previous experience with the drug and its known antiangiogenic activity, consisting mainly of adverse effects such as hypertension, diarrhea, and fatigue.

"Pazopanib maintenance therapy significantly extends time without recurrence and thus increases progression-free survival and delays need for further chemotherapy in ovarian cancer. So it prolongs the time the patient has control over the disease instead of disease having control over the patient," Dr. Du Bois commented in a press briefing.

"This is the first phase III maintenance study demonstrating superior outcome for a targeted therapy in ovarian cancer. Therefore, pazopanib may be a valuable option in the future" for this patient population, he added. "This study will be used for registration purposes, and hopefully we will have this drug available soon."

Dr. Du Bois acknowledged that previous trials have assessed use of bevacizumab (Avastin), another agent having antiangiogenic activity, for maintenance therapy. But bevacizumab was started together with chemotherapy and then continued. "It was not a pure maintenance setting," he said, so it is unclear which component was responsible for benefit.

Additionally, the trial populations differed in residual tumor burden, with 85% of the patients in the pazopanib trial having no evidence of residual disease at the time of enrollment.

Commenting during the press briefing, Dr. Carol Aghajanian, chief of the Gynecologic Medical Oncology Service at the Memorial Sloan-Kettering Cancer Center in New York and an ASCO spokesperson, said that the jury is still out on the optimal targeted agent and the optimal timing of its use in ovarian cancer.

"There has been a lot of discussion in ovarian cancer as to whether the patient should receive these agents as part of their initial treatment, or should you save this benefit for a later time in the course of their disease, at the time of treatment for recurrence or even at the time of treatment for platinum-resistant disease," she said. "But what we do have from the trial presented here by Dr. Du Bois is confirmation that targeting angiogenesis in ovarian cancer is important and effective."

Patients were eligible for the trail, the international intergroup trial AGO-OVAR16 sponsored by GlaxoSmithKline, if they had FIGO stage II to IV ovarian, fallopian tube, or primary peritoneal cancer, had not had progression after resection and completion of at least five cycles of first-line platinum-taxane chemotherapy, and had residual tumors measuring less than 2 cm.

They were randomized evenly to receive 800 mg pazopanib or placebo daily for 24 months.

Pazopanib is a multitargeted tyrosine kinase inhibitor that acts mainly on vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and c-kit signaling. It is approved by the Food and Drug Administration for treatment of kidney cancer and soft tissue sarcoma.

Main trial results showed that after a median follow-up of 24.3 months, median progression-free survival was 17.9 months with pazopanib and 12.3 months with placebo (hazard ratio, 0.77, P = .002). The findings were similar in subgroup analyses, according to Dr. Du Bois, who disclosed that he receives honoraria and research funding from GlaxoSmithKline.

An interim analysis of overall survival showed no significant difference between groups, but only a fifth of the patients had died as of the analysis.

Relative to placebo, pazopanib was associated with a higher incidence of serious adverse events (26% vs. 11%), according to the abstract. Three patients in the pazopanib group and one patient in the placebo group had a fatal serious adverse event.

"Predicting tolerability will be subject to further research," Dr. Du Bois noted.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Patients with serious mental illness who are overweight or obese can lose weight and keep it off with a multifaceted behavioral intervention, a randomized trial showed.

This was one of the conclusions reached by Dr. Gail L. Daumit, lead investigator of ACHIEVE (Randomized Trial of Achieving Healthy Lifestyles in Psych Rehabilitation).

In the trial, Dr. Daumit and her associates tested a physical activity and diet modification intervention among nearly 300 overweight or obese adults attending psychiatric rehabilitation programs. After 18 months, the trial’s intervention group had lost an average of 3.2 kg more than the control group. Moreover, the intervention group continued to lose weight throughout the study period.

"Despite many challenges, with a tailored lifestyle intervention, overweight and obese adults with a serious mental illness can make lifestyle changes and achieve substantial weight loss," Dr. Daumit said while presenting the data at the annual meeting of the American Psychiatric Association. "Our findings really support implementation of a targeted behavioral weight-loss intervention in this high-risk population."

Results of the study were published recently in the New England Journal of Medicine (2013;368:1594-1602).

Dr. Daumit, associate professor of medicine at Johns Hopkins University, Baltimore, said that her findings both resembled and differed from those seen in the PREMIER trial, which tested a behavioral intervention among otherwise healthy individuals with prehypertension or mild hypertension (Ann. Intern. Med. 2006;144:485-95).

In that trial, the intervention group had a similar 2.7-kg greater weight loss than the control group. The PREMIER intervention group, however, had dramatic early weight loss followed by weight gain, whereas the ACHIEVE intervention group continued to lose weight at a more moderate pace throughout the trial.

Dr. Daumit speculated that the trials’ differing trajectories of weight loss might have resulted from the ACHIEVE patients taking more time to engage in their intervention.

"We recruited really all comers, so that in order to get into this trial, you didn’t have to be anywhere on the readiness-for-change spectrum. ... So it may have taken them then more time to make the behavioral changes. But once they made the changes, they were able to keep them," she said. "And maybe there is some limited choice in this population.

"Maybe there were some cognitive issues where they just kind of made the decision and they then just went down that path. They may have less disposable income, [and] less choice about alternatives."

As analyses were conducted according to intention to treat, patients were included even if they never attended a single session, Dr. Daumit pointed out.

"Not everyone came to sessions. So I guess the question is, ‘What’s the dose that’s needed to achieve [weight loss]?’ We are doing some kind of on-treatment analyses now where we are trying to see how much attendance was related to how much weight loss," she said.

One person who attended the session asked what kind of feedback the investigators had received from the trial participants.

"We are still in the process of trying to talk to them about that," Dr. Daumit said. "I think they definitely really liked the exercise ... and that trying to involve more social supports, they believe, would have been more helpful."

Another person in attendance asked how much cardiovascular risk reduction Dr. Daumit thinks was achieved with the weight loss.

"Our study was not powered for this," Dr. Daumit said. However, there were nonsignificant trends whereby the intervention group had roughly 5 mg/dL reductions in total and low-density lipoprotein cholesterol and glucose levels, and a 2-cm reduction in waist circumference, compared with those in the control group.

"Many participants were already taking statins and blood pressure medications and diabetes medications – this wasn’t like just a virgin untreated population," Dr. Daumit said. "So it was difficult to sort out" the intervention effect.

Dr. Daumit also expressed concern about failure of policymakers to include people with serious mental illness in their thinking, particularly in light of this population’s prevalence of overweight and obesity.

"Historically, interventions for cardiovascular disease risk reduction, including weight loss trials with tens of millions of dollars of funding by the [National Institutes of Health] for the overall population, have systematically excluded almost all mental health consumers," she noted. "All of the large trials that really kind of define our nutrition policy or other health behavior intervention policies in the U.S. exclude this population."

The 291 patients in the ACHIEVE trial were recruited from 10 Maryland psychiatric rehabilitation programs that offered meals and encouraged attendance at least twice a week. Those with an active alcohol or substance abuse disorder were excluded.

The patients were randomized evenly to a control group or a group given the 18-month intervention.

The intervention had four components: alternating group and individual weight management sessions offered at least monthly, on-site group physical activity three times weekly, and weigh-ins.

It featured simplified behavioral recommendations (such as avoiding sugary drinks, consuming five fruits and vegetables daily), physical activity goals (on-site exercise three times a week plus exercise on other days for 30 minutes on one’s own), and tracking of eating and physical activity. All program sites were given recommendations for making their menus healthier.

"We did a lot of adapting of the material to the cognitive level of the population so that people who were cognitively impaired or having a lot of mental health symptoms were able to learn in the best way," Dr. Daumit said.

On average, the study patients were 45 years old and had a body mass index of 36 kg/m². The leading mental illnesses were schizophrenia or schizoaffective disorder (seen in 58%) and bipolar disorder (22%).

The patients were taking, on average, three psychotropic medications. Fully 79% were unable to work, and 55% lived in a residential program or with a care provider.

Trial results showed that intervention patients had significantly greater weight loss when compared with their control counterparts (3.4 vs. 0.2 kg, P = .002). The intervention group was more likely to weigh the same as or less than their weight at baseline (64% vs. 49%, P less than .05) and to lose at least 5% of their body weight (38% vs. 23%, P less than .01), she said.

The study was funded by the National Institute of Mental Health. Dr. Daumit disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Patients with serious mental illness who are overweight or obese can lose weight and keep it off with a multifaceted behavioral intervention, a randomized trial showed.

This was one of the conclusions reached by Dr. Gail L. Daumit, lead investigator of ACHIEVE (Randomized Trial of Achieving Healthy Lifestyles in Psych Rehabilitation).

In the trial, Dr. Daumit and her associates tested a physical activity and diet modification intervention among nearly 300 overweight or obese adults attending psychiatric rehabilitation programs. After 18 months, the trial’s intervention group had lost an average of 3.2 kg more than the control group. Moreover, the intervention group continued to lose weight throughout the study period.

"Despite many challenges, with a tailored lifestyle intervention, overweight and obese adults with a serious mental illness can make lifestyle changes and achieve substantial weight loss," Dr. Daumit said while presenting the data at the annual meeting of the American Psychiatric Association. "Our findings really support implementation of a targeted behavioral weight-loss intervention in this high-risk population."

Results of the study were published recently in the New England Journal of Medicine (2013;368:1594-1602).

Dr. Daumit, associate professor of medicine at Johns Hopkins University, Baltimore, said that her findings both resembled and differed from those seen in the PREMIER trial, which tested a behavioral intervention among otherwise healthy individuals with prehypertension or mild hypertension (Ann. Intern. Med. 2006;144:485-95).

In that trial, the intervention group had a similar 2.7-kg greater weight loss than the control group. The PREMIER intervention group, however, had dramatic early weight loss followed by weight gain, whereas the ACHIEVE intervention group continued to lose weight at a more moderate pace throughout the trial.

Dr. Daumit speculated that the trials’ differing trajectories of weight loss might have resulted from the ACHIEVE patients taking more time to engage in their intervention.

"We recruited really all comers, so that in order to get into this trial, you didn’t have to be anywhere on the readiness-for-change spectrum. ... So it may have taken them then more time to make the behavioral changes. But once they made the changes, they were able to keep them," she said. "And maybe there is some limited choice in this population.

"Maybe there were some cognitive issues where they just kind of made the decision and they then just went down that path. They may have less disposable income, [and] less choice about alternatives."

As analyses were conducted according to intention to treat, patients were included even if they never attended a single session, Dr. Daumit pointed out.

"Not everyone came to sessions. So I guess the question is, ‘What’s the dose that’s needed to achieve [weight loss]?’ We are doing some kind of on-treatment analyses now where we are trying to see how much attendance was related to how much weight loss," she said.

One person who attended the session asked what kind of feedback the investigators had received from the trial participants.

"We are still in the process of trying to talk to them about that," Dr. Daumit said. "I think they definitely really liked the exercise ... and that trying to involve more social supports, they believe, would have been more helpful."

Another person in attendance asked how much cardiovascular risk reduction Dr. Daumit thinks was achieved with the weight loss.

"Our study was not powered for this," Dr. Daumit said. However, there were nonsignificant trends whereby the intervention group had roughly 5 mg/dL reductions in total and low-density lipoprotein cholesterol and glucose levels, and a 2-cm reduction in waist circumference, compared with those in the control group.

"Many participants were already taking statins and blood pressure medications and diabetes medications – this wasn’t like just a virgin untreated population," Dr. Daumit said. "So it was difficult to sort out" the intervention effect.

Dr. Daumit also expressed concern about failure of policymakers to include people with serious mental illness in their thinking, particularly in light of this population’s prevalence of overweight and obesity.

"Historically, interventions for cardiovascular disease risk reduction, including weight loss trials with tens of millions of dollars of funding by the [National Institutes of Health] for the overall population, have systematically excluded almost all mental health consumers," she noted. "All of the large trials that really kind of define our nutrition policy or other health behavior intervention policies in the U.S. exclude this population."

The 291 patients in the ACHIEVE trial were recruited from 10 Maryland psychiatric rehabilitation programs that offered meals and encouraged attendance at least twice a week. Those with an active alcohol or substance abuse disorder were excluded.

The patients were randomized evenly to a control group or a group given the 18-month intervention.

The intervention had four components: alternating group and individual weight management sessions offered at least monthly, on-site group physical activity three times weekly, and weigh-ins.

It featured simplified behavioral recommendations (such as avoiding sugary drinks, consuming five fruits and vegetables daily), physical activity goals (on-site exercise three times a week plus exercise on other days for 30 minutes on one’s own), and tracking of eating and physical activity. All program sites were given recommendations for making their menus healthier.

"We did a lot of adapting of the material to the cognitive level of the population so that people who were cognitively impaired or having a lot of mental health symptoms were able to learn in the best way," Dr. Daumit said.

On average, the study patients were 45 years old and had a body mass index of 36 kg/m². The leading mental illnesses were schizophrenia or schizoaffective disorder (seen in 58%) and bipolar disorder (22%).

The patients were taking, on average, three psychotropic medications. Fully 79% were unable to work, and 55% lived in a residential program or with a care provider.

Trial results showed that intervention patients had significantly greater weight loss when compared with their control counterparts (3.4 vs. 0.2 kg, P = .002). The intervention group was more likely to weigh the same as or less than their weight at baseline (64% vs. 49%, P less than .05) and to lose at least 5% of their body weight (38% vs. 23%, P less than .01), she said.

The study was funded by the National Institute of Mental Health. Dr. Daumit disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Patients with serious mental illness who are overweight or obese can lose weight and keep it off with a multifaceted behavioral intervention, a randomized trial showed.

This was one of the conclusions reached by Dr. Gail L. Daumit, lead investigator of ACHIEVE (Randomized Trial of Achieving Healthy Lifestyles in Psych Rehabilitation).

In the trial, Dr. Daumit and her associates tested a physical activity and diet modification intervention among nearly 300 overweight or obese adults attending psychiatric rehabilitation programs. After 18 months, the trial’s intervention group had lost an average of 3.2 kg more than the control group. Moreover, the intervention group continued to lose weight throughout the study period.

"Despite many challenges, with a tailored lifestyle intervention, overweight and obese adults with a serious mental illness can make lifestyle changes and achieve substantial weight loss," Dr. Daumit said while presenting the data at the annual meeting of the American Psychiatric Association. "Our findings really support implementation of a targeted behavioral weight-loss intervention in this high-risk population."

Results of the study were published recently in the New England Journal of Medicine (2013;368:1594-1602).

Dr. Daumit, associate professor of medicine at Johns Hopkins University, Baltimore, said that her findings both resembled and differed from those seen in the PREMIER trial, which tested a behavioral intervention among otherwise healthy individuals with prehypertension or mild hypertension (Ann. Intern. Med. 2006;144:485-95).

In that trial, the intervention group had a similar 2.7-kg greater weight loss than the control group. The PREMIER intervention group, however, had dramatic early weight loss followed by weight gain, whereas the ACHIEVE intervention group continued to lose weight at a more moderate pace throughout the trial.

Dr. Daumit speculated that the trials’ differing trajectories of weight loss might have resulted from the ACHIEVE patients taking more time to engage in their intervention.

"We recruited really all comers, so that in order to get into this trial, you didn’t have to be anywhere on the readiness-for-change spectrum. ... So it may have taken them then more time to make the behavioral changes. But once they made the changes, they were able to keep them," she said. "And maybe there is some limited choice in this population.

"Maybe there were some cognitive issues where they just kind of made the decision and they then just went down that path. They may have less disposable income, [and] less choice about alternatives."

As analyses were conducted according to intention to treat, patients were included even if they never attended a single session, Dr. Daumit pointed out.

"Not everyone came to sessions. So I guess the question is, ‘What’s the dose that’s needed to achieve [weight loss]?’ We are doing some kind of on-treatment analyses now where we are trying to see how much attendance was related to how much weight loss," she said.

One person who attended the session asked what kind of feedback the investigators had received from the trial participants.

"We are still in the process of trying to talk to them about that," Dr. Daumit said. "I think they definitely really liked the exercise ... and that trying to involve more social supports, they believe, would have been more helpful."

Another person in attendance asked how much cardiovascular risk reduction Dr. Daumit thinks was achieved with the weight loss.

"Our study was not powered for this," Dr. Daumit said. However, there were nonsignificant trends whereby the intervention group had roughly 5 mg/dL reductions in total and low-density lipoprotein cholesterol and glucose levels, and a 2-cm reduction in waist circumference, compared with those in the control group.

"Many participants were already taking statins and blood pressure medications and diabetes medications – this wasn’t like just a virgin untreated population," Dr. Daumit said. "So it was difficult to sort out" the intervention effect.

Dr. Daumit also expressed concern about failure of policymakers to include people with serious mental illness in their thinking, particularly in light of this population’s prevalence of overweight and obesity.

"Historically, interventions for cardiovascular disease risk reduction, including weight loss trials with tens of millions of dollars of funding by the [National Institutes of Health] for the overall population, have systematically excluded almost all mental health consumers," she noted. "All of the large trials that really kind of define our nutrition policy or other health behavior intervention policies in the U.S. exclude this population."

The 291 patients in the ACHIEVE trial were recruited from 10 Maryland psychiatric rehabilitation programs that offered meals and encouraged attendance at least twice a week. Those with an active alcohol or substance abuse disorder were excluded.

The patients were randomized evenly to a control group or a group given the 18-month intervention.

The intervention had four components: alternating group and individual weight management sessions offered at least monthly, on-site group physical activity three times weekly, and weigh-ins.

It featured simplified behavioral recommendations (such as avoiding sugary drinks, consuming five fruits and vegetables daily), physical activity goals (on-site exercise three times a week plus exercise on other days for 30 minutes on one’s own), and tracking of eating and physical activity. All program sites were given recommendations for making their menus healthier.

"We did a lot of adapting of the material to the cognitive level of the population so that people who were cognitively impaired or having a lot of mental health symptoms were able to learn in the best way," Dr. Daumit said.

On average, the study patients were 45 years old and had a body mass index of 36 kg/m². The leading mental illnesses were schizophrenia or schizoaffective disorder (seen in 58%) and bipolar disorder (22%).

The patients were taking, on average, three psychotropic medications. Fully 79% were unable to work, and 55% lived in a residential program or with a care provider.

Trial results showed that intervention patients had significantly greater weight loss when compared with their control counterparts (3.4 vs. 0.2 kg, P = .002). The intervention group was more likely to weigh the same as or less than their weight at baseline (64% vs. 49%, P less than .05) and to lose at least 5% of their body weight (38% vs. 23%, P less than .01), she said.

The study was funded by the National Institute of Mental Health. Dr. Daumit disclosed no conflicts of interest related to the research.