Neil Osterweil

WASHINGTON – Exercise can have significant and clinically important mental health benefits for both cancer patients and their caregivers, investigators report.

Among patients with cancer and depression, those who took part in a home-based exercise program had the most rapid improvement of depressive symptoms, whereas patients enrolled in a supervised, structured exercise program had the longest-lasting benefits. Both groups had better resolution of depression than did controls, reported Dr. Gregory T. Levin, an accredited exercise physiologist and postdoctoral research fellow at the University of Calgary (Alta.).

©iStock/thinkstockphotos.com

Exercise should be considered as a component of precision medicine, where we can tailor an exercise intervention for a person depending on their mental health status, their cancer status, or the outcomes that we’re trying to attain, whether that’s [creating] changes in depression or improving muscle strength and muscle function,” Dr. Levin said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Levin and his colleagues conducted a study to determine whether certain types of exercise programs might be more effective than others at reducing symptoms of depression in cancer survivors, compared with controls.

They first screened the participants to ensure that only cancer patients with established clinical depression or elevated depressive symptoms would be invited to take part. Patients were eligible if they reported that they were currently being treated for depression, if they scored more than 10 on the Hospital Anxiety and Depression Scale (HADS), or if they met diagnostic criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) self-rating scale for depression.

They enrolled 32 participants with a mean age of 58.9 years to either a 12-week, clinic-based supervised exercise program (10 patients), a home-based exercise program (8), or usual care (14).

Patients in the supervised exercise group had two weekly sessions of resistance and aerobic training. Patients in the home-based group were given printed material and asked to keep an exercise diary, and were encouraged to exercise at least 150 minutes each week. These patients also received a weekly follow-up phone call. Controls were not told to exercise but were encouraged to maintain usual activities, did not receive printed material, and were not contacted regarding exercise.

For the primary endpoint of depression, both the home-based intervention and the supervised exercise groups had significant reductions in mean HADS scores after 12 weeks, from a baseline of 6.4 to 2.2 for the home-based group (P = .006), and from 6.9 to 2.4 for the supervised group (P = .021). In contrast, controls had a slight increase in scores, from a mean of 7.22 at baseline to 7.76 at week 12.

The most rapid change occurred among the home-based exercisers, who saw the greatest gain during the first 6 weeks. During the second 6 weeks, however, the supervised exercisers saw a sharper decline in scores, compared with the other two groups, possibly because of a loss of motivation among the home-based group.

There was no interaction effect for anxiety over the 12 weeks, but the pattern of decline in anxiety was similar to that seen with depression, with home-based exercisers having a steep decline over the first 6 weeks of the program and then plateauing, while the supervised exercisers saw a greater drop in anxiety scores over the second 6-week period.

Mental health questionnaire scores also favored the exercise groups, compared with controls.

“The exercise program was able to alleviate the depressive symptoms, but the rate of change differed. The home-based [exercise program] initially was favored, and that might be largely due to psychological reasons of distraction, self-efficacy, and mastery, where those self-managed patients take on an exercise regime, are proud of themselves for sticking to it, and notice rapid changes. But then it might become boring and they might stop any time they don’t see changes of such high magnitude,” Dr. Levin said.

Caregiver study

The effects of exercise on the psychological well-being of caregivers was the focus of a scientific poster by Dr. Sylvie Lambert and her colleagues from McGill University in Montreal and the Princess Margaret Cancer Centre in Toronto.

They conducted a systematic review of 14 studies evaluating the effects of exercise and specific types of physical activity on caregivers’ psychosocial well-being. The studies looked at caregivers of patients with cancer and other chronic diseases or disabilities.

They found that overall, exercise has significant beneficial effects on decreasing depression, burden, stress, anger, and anxiety. Most of the interventions used a combination of physical activities, including walking, yoga, meditation, aerobics, tai chi, strength training, stretching, and daily activities such as gardening, housework, etc.

“Physical activity interventions hold promise to improve caregivers’ outcomes, and the findings of this review would suggest that health care providers could promote their use among caregivers,” Dr. Lambert and her colleagues wrote.

WASHINGTON – Exercise can have significant and clinically important mental health benefits for both cancer patients and their caregivers, investigators report.

Among patients with cancer and depression, those who took part in a home-based exercise program had the most rapid improvement of depressive symptoms, whereas patients enrolled in a supervised, structured exercise program had the longest-lasting benefits. Both groups had better resolution of depression than did controls, reported Dr. Gregory T. Levin, an accredited exercise physiologist and postdoctoral research fellow at the University of Calgary (Alta.).

©iStock/thinkstockphotos.com

Exercise should be considered as a component of precision medicine, where we can tailor an exercise intervention for a person depending on their mental health status, their cancer status, or the outcomes that we’re trying to attain, whether that’s [creating] changes in depression or improving muscle strength and muscle function,” Dr. Levin said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Levin and his colleagues conducted a study to determine whether certain types of exercise programs might be more effective than others at reducing symptoms of depression in cancer survivors, compared with controls.

They first screened the participants to ensure that only cancer patients with established clinical depression or elevated depressive symptoms would be invited to take part. Patients were eligible if they reported that they were currently being treated for depression, if they scored more than 10 on the Hospital Anxiety and Depression Scale (HADS), or if they met diagnostic criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) self-rating scale for depression.

They enrolled 32 participants with a mean age of 58.9 years to either a 12-week, clinic-based supervised exercise program (10 patients), a home-based exercise program (8), or usual care (14).

Patients in the supervised exercise group had two weekly sessions of resistance and aerobic training. Patients in the home-based group were given printed material and asked to keep an exercise diary, and were encouraged to exercise at least 150 minutes each week. These patients also received a weekly follow-up phone call. Controls were not told to exercise but were encouraged to maintain usual activities, did not receive printed material, and were not contacted regarding exercise.

For the primary endpoint of depression, both the home-based intervention and the supervised exercise groups had significant reductions in mean HADS scores after 12 weeks, from a baseline of 6.4 to 2.2 for the home-based group (P = .006), and from 6.9 to 2.4 for the supervised group (P = .021). In contrast, controls had a slight increase in scores, from a mean of 7.22 at baseline to 7.76 at week 12.

The most rapid change occurred among the home-based exercisers, who saw the greatest gain during the first 6 weeks. During the second 6 weeks, however, the supervised exercisers saw a sharper decline in scores, compared with the other two groups, possibly because of a loss of motivation among the home-based group.

There was no interaction effect for anxiety over the 12 weeks, but the pattern of decline in anxiety was similar to that seen with depression, with home-based exercisers having a steep decline over the first 6 weeks of the program and then plateauing, while the supervised exercisers saw a greater drop in anxiety scores over the second 6-week period.

Mental health questionnaire scores also favored the exercise groups, compared with controls.

“The exercise program was able to alleviate the depressive symptoms, but the rate of change differed. The home-based [exercise program] initially was favored, and that might be largely due to psychological reasons of distraction, self-efficacy, and mastery, where those self-managed patients take on an exercise regime, are proud of themselves for sticking to it, and notice rapid changes. But then it might become boring and they might stop any time they don’t see changes of such high magnitude,” Dr. Levin said.

Caregiver study

The effects of exercise on the psychological well-being of caregivers was the focus of a scientific poster by Dr. Sylvie Lambert and her colleagues from McGill University in Montreal and the Princess Margaret Cancer Centre in Toronto.

They conducted a systematic review of 14 studies evaluating the effects of exercise and specific types of physical activity on caregivers’ psychosocial well-being. The studies looked at caregivers of patients with cancer and other chronic diseases or disabilities.

They found that overall, exercise has significant beneficial effects on decreasing depression, burden, stress, anger, and anxiety. Most of the interventions used a combination of physical activities, including walking, yoga, meditation, aerobics, tai chi, strength training, stretching, and daily activities such as gardening, housework, etc.

“Physical activity interventions hold promise to improve caregivers’ outcomes, and the findings of this review would suggest that health care providers could promote their use among caregivers,” Dr. Lambert and her colleagues wrote.

WASHINGTON – Exercise can have significant and clinically important mental health benefits for both cancer patients and their caregivers, investigators report.

Among patients with cancer and depression, those who took part in a home-based exercise program had the most rapid improvement of depressive symptoms, whereas patients enrolled in a supervised, structured exercise program had the longest-lasting benefits. Both groups had better resolution of depression than did controls, reported Dr. Gregory T. Levin, an accredited exercise physiologist and postdoctoral research fellow at the University of Calgary (Alta.).

©iStock/thinkstockphotos.com

Exercise should be considered as a component of precision medicine, where we can tailor an exercise intervention for a person depending on their mental health status, their cancer status, or the outcomes that we’re trying to attain, whether that’s [creating] changes in depression or improving muscle strength and muscle function,” Dr. Levin said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Levin and his colleagues conducted a study to determine whether certain types of exercise programs might be more effective than others at reducing symptoms of depression in cancer survivors, compared with controls.

They first screened the participants to ensure that only cancer patients with established clinical depression or elevated depressive symptoms would be invited to take part. Patients were eligible if they reported that they were currently being treated for depression, if they scored more than 10 on the Hospital Anxiety and Depression Scale (HADS), or if they met diagnostic criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) self-rating scale for depression.

They enrolled 32 participants with a mean age of 58.9 years to either a 12-week, clinic-based supervised exercise program (10 patients), a home-based exercise program (8), or usual care (14).

Patients in the supervised exercise group had two weekly sessions of resistance and aerobic training. Patients in the home-based group were given printed material and asked to keep an exercise diary, and were encouraged to exercise at least 150 minutes each week. These patients also received a weekly follow-up phone call. Controls were not told to exercise but were encouraged to maintain usual activities, did not receive printed material, and were not contacted regarding exercise.

For the primary endpoint of depression, both the home-based intervention and the supervised exercise groups had significant reductions in mean HADS scores after 12 weeks, from a baseline of 6.4 to 2.2 for the home-based group (P = .006), and from 6.9 to 2.4 for the supervised group (P = .021). In contrast, controls had a slight increase in scores, from a mean of 7.22 at baseline to 7.76 at week 12.

The most rapid change occurred among the home-based exercisers, who saw the greatest gain during the first 6 weeks. During the second 6 weeks, however, the supervised exercisers saw a sharper decline in scores, compared with the other two groups, possibly because of a loss of motivation among the home-based group.

There was no interaction effect for anxiety over the 12 weeks, but the pattern of decline in anxiety was similar to that seen with depression, with home-based exercisers having a steep decline over the first 6 weeks of the program and then plateauing, while the supervised exercisers saw a greater drop in anxiety scores over the second 6-week period.

Mental health questionnaire scores also favored the exercise groups, compared with controls.

“The exercise program was able to alleviate the depressive symptoms, but the rate of change differed. The home-based [exercise program] initially was favored, and that might be largely due to psychological reasons of distraction, self-efficacy, and mastery, where those self-managed patients take on an exercise regime, are proud of themselves for sticking to it, and notice rapid changes. But then it might become boring and they might stop any time they don’t see changes of such high magnitude,” Dr. Levin said.

Caregiver study

The effects of exercise on the psychological well-being of caregivers was the focus of a scientific poster by Dr. Sylvie Lambert and her colleagues from McGill University in Montreal and the Princess Margaret Cancer Centre in Toronto.

They conducted a systematic review of 14 studies evaluating the effects of exercise and specific types of physical activity on caregivers’ psychosocial well-being. The studies looked at caregivers of patients with cancer and other chronic diseases or disabilities.

They found that overall, exercise has significant beneficial effects on decreasing depression, burden, stress, anger, and anxiety. Most of the interventions used a combination of physical activities, including walking, yoga, meditation, aerobics, tai chi, strength training, stretching, and daily activities such as gardening, housework, etc.

“Physical activity interventions hold promise to improve caregivers’ outcomes, and the findings of this review would suggest that health care providers could promote their use among caregivers,” Dr. Lambert and her colleagues wrote.

WASHINGTON – Treating depression in cancer patients has the potential to simultaneously improve the patients’ mental health while reducing health care costs, investigators say.

Patients with cancer and depression have significantly more emergency and nonemergency visits and are more likely to be hospitalized as well as rehospitalized within 30 days than nondepressed cancer patients, suggesting that active treatment of depression in cancer patients can pay off in both better patient care and lower costs, reported Dr. Brent Mausbach, a clinical psychologist at the University of California, San Diego Moores Cancer Center.

“If we’re looking at 1,000 depressed cancer patients and we compare them to 1,000 nondepressed cancer patients, what this essentially equates to is over $4 million in extra cost – and this only includes the cost of the emergency department and hospitalizations; it does not include the cost of other visits that these patients may be making,” he said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Mausbach and colleagues took a retrospective look at the charts of 5,055 patients with cancer treated at their center in 2011, including 561 with a diagnosis of depression and 4,494 with no depression.

The investigators counted the total number of visits, emergency department (ED) visits, and 30-day readmissions, and calculated the probability that a randomly selected depressed patient would have more visits than a randomly selected nondepressed patient.

They controlled for patient demographics (age, sex, and race/ethnicity), insurance status, months since cancer diagnosis, comorbidities, and metastasis.

They found that patients who were depressed had a mean of 26.9 visits over 12 months vs. 15 for nondepressed patients. Compared with nondepressed patients, depressed patients had a 72.5% probability of having more health care visits.

The median number of visits to the health care system among depressed cancer patients was 21, compared with 8 for nondepressed patients.

In all, 28.3% of depressed patients had one or more emergency department visits for any reason, compared with 11.5% of nondepressed patients (odds ratio, 3.05; adjusted OR, 2.45).

Similarly, depressed patients were significantly more likely to be hospitalized than their nondepressed counterparts (OR, 2.41; aOR, 1.81), and to be rehospitalized within 30 days (OR, 2.31; aOR, 2.03).

Patients with depression also had significantly longer hospital stays, at a mean of 6.1 vs. 4.7 for those without depression.

“For the emergency department, hospitalization, and 30-day rehospitalization data, we think the effects seemed pretty consistent across all those outcomes. Essentially there was about a doubling of the risk for patients who have depression for all of those outcomes relative to patients without depression,” Dr. Mausbach said.

He noted that there is an “overwhelming temptation” for investigators to assume the between-person effects they saw could translate directly into within-person effects. For example, an observer might extrapolate from the data that treating depression in an individual patients could halve that patient’s use of health care resources, but a longitudinal study would be required to correctly address that question, he said.

Additionally, the study was limited by a lack of data on cancer stage and grade, and by the uncertainties surrounding a chart-recorded diagnosis of depression.

“Can we treat depression and then have an impact on lower health care use and overall costs? We need to demonstrate this using clinical trials or pseudo-experimental designs, which would include taking a look at people who actually received psychotherapy or medications, and checking to see whether by using these treatments they actually had a reduction in total number of health care visits,” Dr. Mausbach said.

The study was institutionally supported. The authors reported having no conflicts of interest.

WASHINGTON – Treating depression in cancer patients has the potential to simultaneously improve the patients’ mental health while reducing health care costs, investigators say.

Patients with cancer and depression have significantly more emergency and nonemergency visits and are more likely to be hospitalized as well as rehospitalized within 30 days than nondepressed cancer patients, suggesting that active treatment of depression in cancer patients can pay off in both better patient care and lower costs, reported Dr. Brent Mausbach, a clinical psychologist at the University of California, San Diego Moores Cancer Center.

“If we’re looking at 1,000 depressed cancer patients and we compare them to 1,000 nondepressed cancer patients, what this essentially equates to is over $4 million in extra cost – and this only includes the cost of the emergency department and hospitalizations; it does not include the cost of other visits that these patients may be making,” he said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Mausbach and colleagues took a retrospective look at the charts of 5,055 patients with cancer treated at their center in 2011, including 561 with a diagnosis of depression and 4,494 with no depression.

The investigators counted the total number of visits, emergency department (ED) visits, and 30-day readmissions, and calculated the probability that a randomly selected depressed patient would have more visits than a randomly selected nondepressed patient.

They controlled for patient demographics (age, sex, and race/ethnicity), insurance status, months since cancer diagnosis, comorbidities, and metastasis.

They found that patients who were depressed had a mean of 26.9 visits over 12 months vs. 15 for nondepressed patients. Compared with nondepressed patients, depressed patients had a 72.5% probability of having more health care visits.

The median number of visits to the health care system among depressed cancer patients was 21, compared with 8 for nondepressed patients.

In all, 28.3% of depressed patients had one or more emergency department visits for any reason, compared with 11.5% of nondepressed patients (odds ratio, 3.05; adjusted OR, 2.45).

Similarly, depressed patients were significantly more likely to be hospitalized than their nondepressed counterparts (OR, 2.41; aOR, 1.81), and to be rehospitalized within 30 days (OR, 2.31; aOR, 2.03).

Patients with depression also had significantly longer hospital stays, at a mean of 6.1 vs. 4.7 for those without depression.

“For the emergency department, hospitalization, and 30-day rehospitalization data, we think the effects seemed pretty consistent across all those outcomes. Essentially there was about a doubling of the risk for patients who have depression for all of those outcomes relative to patients without depression,” Dr. Mausbach said.

He noted that there is an “overwhelming temptation” for investigators to assume the between-person effects they saw could translate directly into within-person effects. For example, an observer might extrapolate from the data that treating depression in an individual patients could halve that patient’s use of health care resources, but a longitudinal study would be required to correctly address that question, he said.

Additionally, the study was limited by a lack of data on cancer stage and grade, and by the uncertainties surrounding a chart-recorded diagnosis of depression.

“Can we treat depression and then have an impact on lower health care use and overall costs? We need to demonstrate this using clinical trials or pseudo-experimental designs, which would include taking a look at people who actually received psychotherapy or medications, and checking to see whether by using these treatments they actually had a reduction in total number of health care visits,” Dr. Mausbach said.

The study was institutionally supported. The authors reported having no conflicts of interest.

WASHINGTON – Treating depression in cancer patients has the potential to simultaneously improve the patients’ mental health while reducing health care costs, investigators say.

Patients with cancer and depression have significantly more emergency and nonemergency visits and are more likely to be hospitalized as well as rehospitalized within 30 days than nondepressed cancer patients, suggesting that active treatment of depression in cancer patients can pay off in both better patient care and lower costs, reported Dr. Brent Mausbach, a clinical psychologist at the University of California, San Diego Moores Cancer Center.

“If we’re looking at 1,000 depressed cancer patients and we compare them to 1,000 nondepressed cancer patients, what this essentially equates to is over $4 million in extra cost – and this only includes the cost of the emergency department and hospitalizations; it does not include the cost of other visits that these patients may be making,” he said at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Mausbach and colleagues took a retrospective look at the charts of 5,055 patients with cancer treated at their center in 2011, including 561 with a diagnosis of depression and 4,494 with no depression.

The investigators counted the total number of visits, emergency department (ED) visits, and 30-day readmissions, and calculated the probability that a randomly selected depressed patient would have more visits than a randomly selected nondepressed patient.

They controlled for patient demographics (age, sex, and race/ethnicity), insurance status, months since cancer diagnosis, comorbidities, and metastasis.

They found that patients who were depressed had a mean of 26.9 visits over 12 months vs. 15 for nondepressed patients. Compared with nondepressed patients, depressed patients had a 72.5% probability of having more health care visits.

The median number of visits to the health care system among depressed cancer patients was 21, compared with 8 for nondepressed patients.

In all, 28.3% of depressed patients had one or more emergency department visits for any reason, compared with 11.5% of nondepressed patients (odds ratio, 3.05; adjusted OR, 2.45).

Similarly, depressed patients were significantly more likely to be hospitalized than their nondepressed counterparts (OR, 2.41; aOR, 1.81), and to be rehospitalized within 30 days (OR, 2.31; aOR, 2.03).

Patients with depression also had significantly longer hospital stays, at a mean of 6.1 vs. 4.7 for those without depression.

“For the emergency department, hospitalization, and 30-day rehospitalization data, we think the effects seemed pretty consistent across all those outcomes. Essentially there was about a doubling of the risk for patients who have depression for all of those outcomes relative to patients without depression,” Dr. Mausbach said.

He noted that there is an “overwhelming temptation” for investigators to assume the between-person effects they saw could translate directly into within-person effects. For example, an observer might extrapolate from the data that treating depression in an individual patients could halve that patient’s use of health care resources, but a longitudinal study would be required to correctly address that question, he said.

Additionally, the study was limited by a lack of data on cancer stage and grade, and by the uncertainties surrounding a chart-recorded diagnosis of depression.

“Can we treat depression and then have an impact on lower health care use and overall costs? We need to demonstrate this using clinical trials or pseudo-experimental designs, which would include taking a look at people who actually received psychotherapy or medications, and checking to see whether by using these treatments they actually had a reduction in total number of health care visits,” Dr. Mausbach said.

The study was institutionally supported. The authors reported having no conflicts of interest.

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Regional nodal irradiation added to whole-breast or thoracic wall irradiation in an unselected patient population reduces breast cancer recurrence rates and improves disease-free and distant disease-free survival, but has little or no effect on overall survival, results of two large, long-term, randomized clinical trials show.

In the MA.20 trial, there was no significant difference in overall survival at 10-year follow-up between women with early breast cancer treated with breast-conserving surgery, adjuvant systemic therapy, and whole-breast irradiation with or without regional nodal irradiation.

Women who received nodal irradiation had significantly better disease-free survival, but at the cost of higher rates of pneumonitis and lymphedema, report Dr. Timothy J. Whelan from the Juravinski Cancer Centre at Hamilton Health Sciences in Hamilton, Ont., and his colleagues in the July 23 issue of the New England Journal of Medicine (doi:10.1056/NEJMoa1415340).

In the EORTC 22922/10925 study, investigators in the European Organization for Research and Treatment of Cancer randomly assigned women with a centrally or medially located primary tumor irrespective of axillary involvement, or an externally located tumor with axillary involvement, to receive either whole-breast or thoracic wall irradiation alone, or with the addition of regional nodal irradiation.

As in the Canadian study, the investigators found no difference in overall survival at 10 years between women who received nodal irradiation and those who did not. Similarly, the EORTC investigators found that rates of disease-free survival and distant disease-free survival were better among women who received nodal irradiation. The nodal irradiation group also had a significantly lower rate of breast cancer–specific death. The European investigators, however, felt that “the acute side effects of regional nodal irradiation were modest.” The study, by Dr. Philip M. Poortmans of Radboud University in Nijmegen, the Netherlands, also appears in the New England Journal of Medicine (2015 July 23 [doi:10.1056/NEJMoa1415369]).

“The trials by Whelan et al. and Poortmans et al. show the possibilities and the limits of more extensive regional treatment of breast cancer in an unselected population and frame the discussion for the next generation of individualized treatment programs, built largely on genomic characterization of tumor biology,” write Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston and Dr. Monica Morrow of the Memorial Sloan Kettering Cancer in New York, in an accompanying editorial.

MA.20

From March 2000 through February 2007, Dr. Whelan and colleagues in the MA.20 trial enrolled 1,832 women with node-positive or high-risk node-negative cancer treated with breast-conserving surgery and adjuvant systemic therapy. The women were randomly assigned, 916 in each group, to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph node), or whole-breast irradiation alone (controls).

At 10-year follow-up, overall survival rates were similar, at 82.8% in the nodal irradiation group and 81.8% in the control group (hazard ratio, 0.91, P =.38). However, as noted before, the rate of disease-free survival was 82% in the nodal irradiation group, compared with 77% in the control group (HR, 0.76, P = .01).

When they looked at adverse effects of the additional radiation, however, the investigators found that rates of grade 2 or greater acute pneumonitis were 1.2% among nodal irradiation patients, compared with just 0.2% of controls (P = .001). Lymphedema rates were also nearly twice as high among nodally irradiated patients (8.4% vs. 4.5%, respectively, P = .001).

The authors concluded that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. “Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” they wrote.

EORTC 22922/10925

In this trial, a total of 4004 women were randomized from 1996 through 2004. The patients had either centrally or medially located primary tumors, irrespective of axillary involvement, or an externally located tumor with axillary involvement.

Most of the women (76.1%) had breast-conserving surgery. Of those who underwent radical mastectomy 73.4% of the patients in both the nodal irradiation and control groups underwent chest wall irradiation.

All but 1% of patients with node-positive disease received adjuvant systemic therapy, as did 66.3% of patients with node-negative disease.

At 10 years, overall survival was not significantly different between the two groups, at 82.3% in the nodal irradiation group and 80.7% in the control group (HR, 0.87; P = 0.06).

As in the Canadian trial, the rate of disease-free survival was significantly better among patients who received nodal-irradiation, at 72.1% vs. 69.1% (HR for disease progression or death, 0.89; P = .04).

Regional nodal irradiation was also associated with significantly better distant disease-free survival (78.0% vs. 75.0%; HR, 0.86; P = .02), and breast cancer mortality (12.5% vs.14.4%; HR, 0.82; P = .02).

The rate of pulmonary fibrosis at 10 years was higher among patients in the nodal irradiation group (4.4% vs. 1.7%, P < .001). Rates of cardiac fibrosis and cardiac disease were also numerically but not significantly higher among patients who received nodal irradiation. There were no other significant differences between the groups in other late toxic effects or performance status, the authors reported.

“Our data do not apply to patients with lateral node-negative cancers, which is the largest patient subgroup in industrialized countries,” they noted.

The MA.20 study was supported by grants from the Canadian Cancer Society Research Institute, NCIC Clinical Trials Group, Canadian Breast Cancer Research Initiative, U.S. National Cancer Institute, and the Cancer Council of Victoria, New South Wales, Queensland, and South Australia. Dr. Whelan reported receiving fees for serving on an advisory board from Genomic Health and testing reagents for another study from NanoString Technologies. The EORTC study was supported by the EORTC and national health agencies. Dr. Poortmans reported no conflicts of interest. Dr. Burstein reported no conflicts of interest. Dr. Morrow reported personal fees from Genomic Health outside the submitted work.

Body mass index should not be a major determinant of whether women with ovarian cancer receive reduced-dose chemotherapy, investigators say.

Because body surface area calculations are used to determine the dose of paclitaxel in the standard paclitaxel and carboplatin regimen for ovarian cancer, some centers treat obese women with reduced doses, in the belief that dose reduction can provide clinical benefit while minimizing toxicity. Normal-weight women may also have dose reductions when they experience serious adverse events following early cycles of chemotherapy.

But those dose reductions may be compromising survival, caution Dr. Elisa V. Bandera from the Robert Wood Johnson Medical School in New Brunswick, N.J., and her colleagues. They found that in a cohort of 806 obese and normal-weight women with epithelial ovarian cancer receiving first-line paclitaxel and carboplatin with curative intent, women with class 3 obesity (body mass index >40 kg/mg²) received 38% lower doses of paclitaxel, and 45% lower doses of carboplatin than did normal-weight women, and also received lower relative dose intensity (RDI) than did normal-weight women for each agent separately and for the combination regimen.

The mean average RDI was 73.7% for women in obese class 3, compared with 88.2% for normal-weight women (P < .001). Average RDI lower than 70% was associated with both worse overall survival (OS; hazard ratio, 1.62; 95% confidence interval, 1.10-2.37) and worse ovarian cancer-specific survival (HR, 1.69; 95% CI, 1.12-2.55), the investigators report (JAMA Oncology 2015 July 2 [doi: 10.1001/jamaoncol.2015.1796]).

Although women who were obese at diagnosis appeared to have better survival than normal-weight women did in an analysis adjusted for prognostic factors, that survival advantage disappeared with dose reduction.

In a multivariable analysis looking at the joint effects of BMI and average RDI, the authors found that normal-weight women who received less than 85% of the standard dose had a 1.5-fold higher risk for mortality than did similar women who did not have dose reduction. For each category of BMI, patients who had average RDI less than 85% of normal had worse survival than did similar-sized patients with no dose-reductions.

“In this study we found that obese patients with ovarian cancer received considerably less paclitaxel and carboplatin/kg of body weight and lower RDI for each chemotherapy agent and for the combined regimen. We also found that the strongest predictor of dose reduction, defined as an RDI below 85%, was a high BMI. Dose reduction was associated with reduced survival time, particularly for normal-weight women. This association was apparent even after accounting for diagnostic and prognostic factors such as stage of disease, comorbid conditions, or posttreatment CA125 levels, a marker of residual disease,” they write.

Body mass index should not be a major determinant of whether women with ovarian cancer receive reduced-dose chemotherapy, investigators say.

Because body surface area calculations are used to determine the dose of paclitaxel in the standard paclitaxel and carboplatin regimen for ovarian cancer, some centers treat obese women with reduced doses, in the belief that dose reduction can provide clinical benefit while minimizing toxicity. Normal-weight women may also have dose reductions when they experience serious adverse events following early cycles of chemotherapy.

But those dose reductions may be compromising survival, caution Dr. Elisa V. Bandera from the Robert Wood Johnson Medical School in New Brunswick, N.J., and her colleagues. They found that in a cohort of 806 obese and normal-weight women with epithelial ovarian cancer receiving first-line paclitaxel and carboplatin with curative intent, women with class 3 obesity (body mass index >40 kg/mg²) received 38% lower doses of paclitaxel, and 45% lower doses of carboplatin than did normal-weight women, and also received lower relative dose intensity (RDI) than did normal-weight women for each agent separately and for the combination regimen.

The mean average RDI was 73.7% for women in obese class 3, compared with 88.2% for normal-weight women (P < .001). Average RDI lower than 70% was associated with both worse overall survival (OS; hazard ratio, 1.62; 95% confidence interval, 1.10-2.37) and worse ovarian cancer-specific survival (HR, 1.69; 95% CI, 1.12-2.55), the investigators report (JAMA Oncology 2015 July 2 [doi: 10.1001/jamaoncol.2015.1796]).

Although women who were obese at diagnosis appeared to have better survival than normal-weight women did in an analysis adjusted for prognostic factors, that survival advantage disappeared with dose reduction.

In a multivariable analysis looking at the joint effects of BMI and average RDI, the authors found that normal-weight women who received less than 85% of the standard dose had a 1.5-fold higher risk for mortality than did similar women who did not have dose reduction. For each category of BMI, patients who had average RDI less than 85% of normal had worse survival than did similar-sized patients with no dose-reductions.

“In this study we found that obese patients with ovarian cancer received considerably less paclitaxel and carboplatin/kg of body weight and lower RDI for each chemotherapy agent and for the combined regimen. We also found that the strongest predictor of dose reduction, defined as an RDI below 85%, was a high BMI. Dose reduction was associated with reduced survival time, particularly for normal-weight women. This association was apparent even after accounting for diagnostic and prognostic factors such as stage of disease, comorbid conditions, or posttreatment CA125 levels, a marker of residual disease,” they write.

Body mass index should not be a major determinant of whether women with ovarian cancer receive reduced-dose chemotherapy, investigators say.

Because body surface area calculations are used to determine the dose of paclitaxel in the standard paclitaxel and carboplatin regimen for ovarian cancer, some centers treat obese women with reduced doses, in the belief that dose reduction can provide clinical benefit while minimizing toxicity. Normal-weight women may also have dose reductions when they experience serious adverse events following early cycles of chemotherapy.

But those dose reductions may be compromising survival, caution Dr. Elisa V. Bandera from the Robert Wood Johnson Medical School in New Brunswick, N.J., and her colleagues. They found that in a cohort of 806 obese and normal-weight women with epithelial ovarian cancer receiving first-line paclitaxel and carboplatin with curative intent, women with class 3 obesity (body mass index >40 kg/mg²) received 38% lower doses of paclitaxel, and 45% lower doses of carboplatin than did normal-weight women, and also received lower relative dose intensity (RDI) than did normal-weight women for each agent separately and for the combination regimen.

The mean average RDI was 73.7% for women in obese class 3, compared with 88.2% for normal-weight women (P < .001). Average RDI lower than 70% was associated with both worse overall survival (OS; hazard ratio, 1.62; 95% confidence interval, 1.10-2.37) and worse ovarian cancer-specific survival (HR, 1.69; 95% CI, 1.12-2.55), the investigators report (JAMA Oncology 2015 July 2 [doi: 10.1001/jamaoncol.2015.1796]).

Although women who were obese at diagnosis appeared to have better survival than normal-weight women did in an analysis adjusted for prognostic factors, that survival advantage disappeared with dose reduction.

In a multivariable analysis looking at the joint effects of BMI and average RDI, the authors found that normal-weight women who received less than 85% of the standard dose had a 1.5-fold higher risk for mortality than did similar women who did not have dose reduction. For each category of BMI, patients who had average RDI less than 85% of normal had worse survival than did similar-sized patients with no dose-reductions.

“In this study we found that obese patients with ovarian cancer received considerably less paclitaxel and carboplatin/kg of body weight and lower RDI for each chemotherapy agent and for the combined regimen. We also found that the strongest predictor of dose reduction, defined as an RDI below 85%, was a high BMI. Dose reduction was associated with reduced survival time, particularly for normal-weight women. This association was apparent even after accounting for diagnostic and prognostic factors such as stage of disease, comorbid conditions, or posttreatment CA125 levels, a marker of residual disease,” they write.

ALEXANDRIA, VA. – The American Society of Clinical Oncology has initiated an ambitious campaign designed to wring order out of the current chaos surrounding the efficacy, toxicities, and costs of emerging therapies for cancer.

ASCO is inviting clinicians and other stakeholders to comment on the initial version of its Value Framework, published June 22, 2015 in the Journal of Clinical Oncology.

“We developed the framework because costs are increasing, and our patients are clearly feeling the impact, and we’ve heard about that directly from patients and their doctors,” said ASCO Chief Medical Officer Richard L. Schilsky at a media briefing announcing publication of the first version of the framework.

The costs of cancer care are growing rapidly, and are expected to increase from approximately $125 billion annually in 2010 to $158 billion by 2020. Cancer drugs are the fastest-growing components of that cost. New cancer drugs on average cost about $10,000 per month, compared with half that amount just 10 years ago, Dr. Schilsky said.

“Some new drugs now exceed $30,000 per month, and as we look to the future of using these new drugs in combination the costs will be even greater,” he said

Out-of-pocket costs for patients are also on the rise. The total out-of-pocket burden is greater for patients with cancer than with other chronic diseases, regardless of the type of insurance the patient has.

“Many cancer patients are facing severe financial strain, even bankruptcy in some cases. In fact, people with cancer are about 2½ times more likely to face bankruptcy than those without cancer,” Dr. Schilsky noted.

He pointed to a 2013 study of financial toxicity among cancer patients, which found that among patients surveyed, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether in order to save on the costs of their care.

How it works

The Value Framework is intended to serve as a standardized system of information on the relative benefits, toxicities, and costs of new therapies as compared with existing therapies in randomized clinical trials.

The framework is specifically built around the comparative trial, with different methodologies to evaluate therapies for advanced/metastatic disease and treatments used with curative intent in the adjuvant setting.

“This is not meant to be a ranking or a calculator for individual drugs. It’s a way to provide information in a standardized and objective way to both physicians and patients about the value of new treatment options that emerge from clinical trials comparing a standard of care to a new treatment option,” said Dr. Lowell E. Schnipper, chair of ASCO’s Value in Cancer Care Task Force.

“I want to be clear: this is not a way of ranking drugs; this is simply a way of understanding the outcome of a clinical trial,” he said at the briefing.

The frameworks use a scoring system to award or subtract points to a specific therapy based on clinical benefit and toxicity, with the two scores combined to generate a Net Health Benefit score that will then be compared with the direct cost of the treatment.

Clinical benefit

For the adjuvant framework, a score of 1-5 for overall survival (OS) will be assigned based on the hazard ratio when the treatment is compared to the standard of care. If the trial does not report OS data, the hazard ratio for disease-free survival (DFS) will be used instead. The categorical score is multiplied, or weighted, by a factor of 16 for OS and 15 for DFS. In this and in the advanced disease framework, the maximum weight of the benefit on survival will be 80 points (16 x 5).

In the advanced/metastatic framework, clinical benefit will be scored based on fractional improvement in median OS over the standard of a care for a specific clinical scenario. As with the adjuvant framework, OS is considered first, DFS if OS is not available, and if neither is available (for example, in a single-arm trial), response rate will be used. In this framework, OS is weighted by a factor of 16, PFS by 11 “because it is a less clinically meaningful end point and is not always a surrogate for OS,” the framework creators note. Response rate will be weighted by 8, an acknowledgment that clinical responses do not always translate into improvements in OS.

In both frameworks, toxicities will be determined relative to the comparator regimen or drug, with a categorical value ranging from –20 (for substantially less well tolerated) to +20 (substantially better).

For the advanced/metastatic disease framework, a treatment or regimen can earn “bonus” points if it can be demonstrated to provide a statistically significant improvement in either palliation of symptoms and/or treatment-free intervals, compared with the control treatment in a prospective clinical trial.

Scores and cost

The Net Health Benefit score will be derived from the combination of the clinical benefit and toxicity score, plus points for regimens designed to treat advanced cancer. The maximum achievable scores are 100 for adjuvant therapies and 130 for advanced/metastatic therapies.

Cost estimates included in the valuation process will include both drug acquisition costs and costs to patients.

ASCO is inviting comments via an online survey through August 21, 2015.

ALEXANDRIA, VA. – The American Society of Clinical Oncology has initiated an ambitious campaign designed to wring order out of the current chaos surrounding the efficacy, toxicities, and costs of emerging therapies for cancer.

ASCO is inviting clinicians and other stakeholders to comment on the initial version of its Value Framework, published June 22, 2015 in the Journal of Clinical Oncology.

“We developed the framework because costs are increasing, and our patients are clearly feeling the impact, and we’ve heard about that directly from patients and their doctors,” said ASCO Chief Medical Officer Richard L. Schilsky at a media briefing announcing publication of the first version of the framework.

The costs of cancer care are growing rapidly, and are expected to increase from approximately $125 billion annually in 2010 to $158 billion by 2020. Cancer drugs are the fastest-growing components of that cost. New cancer drugs on average cost about $10,000 per month, compared with half that amount just 10 years ago, Dr. Schilsky said.

“Some new drugs now exceed $30,000 per month, and as we look to the future of using these new drugs in combination the costs will be even greater,” he said

Out-of-pocket costs for patients are also on the rise. The total out-of-pocket burden is greater for patients with cancer than with other chronic diseases, regardless of the type of insurance the patient has.

“Many cancer patients are facing severe financial strain, even bankruptcy in some cases. In fact, people with cancer are about 2½ times more likely to face bankruptcy than those without cancer,” Dr. Schilsky noted.

He pointed to a 2013 study of financial toxicity among cancer patients, which found that among patients surveyed, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether in order to save on the costs of their care.

How it works

The Value Framework is intended to serve as a standardized system of information on the relative benefits, toxicities, and costs of new therapies as compared with existing therapies in randomized clinical trials.

The framework is specifically built around the comparative trial, with different methodologies to evaluate therapies for advanced/metastatic disease and treatments used with curative intent in the adjuvant setting.

“This is not meant to be a ranking or a calculator for individual drugs. It’s a way to provide information in a standardized and objective way to both physicians and patients about the value of new treatment options that emerge from clinical trials comparing a standard of care to a new treatment option,” said Dr. Lowell E. Schnipper, chair of ASCO’s Value in Cancer Care Task Force.

“I want to be clear: this is not a way of ranking drugs; this is simply a way of understanding the outcome of a clinical trial,” he said at the briefing.

The frameworks use a scoring system to award or subtract points to a specific therapy based on clinical benefit and toxicity, with the two scores combined to generate a Net Health Benefit score that will then be compared with the direct cost of the treatment.

Clinical benefit

For the adjuvant framework, a score of 1-5 for overall survival (OS) will be assigned based on the hazard ratio when the treatment is compared to the standard of care. If the trial does not report OS data, the hazard ratio for disease-free survival (DFS) will be used instead. The categorical score is multiplied, or weighted, by a factor of 16 for OS and 15 for DFS. In this and in the advanced disease framework, the maximum weight of the benefit on survival will be 80 points (16 x 5).

In the advanced/metastatic framework, clinical benefit will be scored based on fractional improvement in median OS over the standard of a care for a specific clinical scenario. As with the adjuvant framework, OS is considered first, DFS if OS is not available, and if neither is available (for example, in a single-arm trial), response rate will be used. In this framework, OS is weighted by a factor of 16, PFS by 11 “because it is a less clinically meaningful end point and is not always a surrogate for OS,” the framework creators note. Response rate will be weighted by 8, an acknowledgment that clinical responses do not always translate into improvements in OS.

In both frameworks, toxicities will be determined relative to the comparator regimen or drug, with a categorical value ranging from –20 (for substantially less well tolerated) to +20 (substantially better).

For the advanced/metastatic disease framework, a treatment or regimen can earn “bonus” points if it can be demonstrated to provide a statistically significant improvement in either palliation of symptoms and/or treatment-free intervals, compared with the control treatment in a prospective clinical trial.

Scores and cost

The Net Health Benefit score will be derived from the combination of the clinical benefit and toxicity score, plus points for regimens designed to treat advanced cancer. The maximum achievable scores are 100 for adjuvant therapies and 130 for advanced/metastatic therapies.

Cost estimates included in the valuation process will include both drug acquisition costs and costs to patients.

ASCO is inviting comments via an online survey through August 21, 2015.

ALEXANDRIA, VA. – The American Society of Clinical Oncology has initiated an ambitious campaign designed to wring order out of the current chaos surrounding the efficacy, toxicities, and costs of emerging therapies for cancer.

ASCO is inviting clinicians and other stakeholders to comment on the initial version of its Value Framework, published June 22, 2015 in the Journal of Clinical Oncology.

“We developed the framework because costs are increasing, and our patients are clearly feeling the impact, and we’ve heard about that directly from patients and their doctors,” said ASCO Chief Medical Officer Richard L. Schilsky at a media briefing announcing publication of the first version of the framework.

The costs of cancer care are growing rapidly, and are expected to increase from approximately $125 billion annually in 2010 to $158 billion by 2020. Cancer drugs are the fastest-growing components of that cost. New cancer drugs on average cost about $10,000 per month, compared with half that amount just 10 years ago, Dr. Schilsky said.

“Some new drugs now exceed $30,000 per month, and as we look to the future of using these new drugs in combination the costs will be even greater,” he said

Out-of-pocket costs for patients are also on the rise. The total out-of-pocket burden is greater for patients with cancer than with other chronic diseases, regardless of the type of insurance the patient has.

“Many cancer patients are facing severe financial strain, even bankruptcy in some cases. In fact, people with cancer are about 2½ times more likely to face bankruptcy than those without cancer,” Dr. Schilsky noted.

He pointed to a 2013 study of financial toxicity among cancer patients, which found that among patients surveyed, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether in order to save on the costs of their care.

How it works

The Value Framework is intended to serve as a standardized system of information on the relative benefits, toxicities, and costs of new therapies as compared with existing therapies in randomized clinical trials.

The framework is specifically built around the comparative trial, with different methodologies to evaluate therapies for advanced/metastatic disease and treatments used with curative intent in the adjuvant setting.

“This is not meant to be a ranking or a calculator for individual drugs. It’s a way to provide information in a standardized and objective way to both physicians and patients about the value of new treatment options that emerge from clinical trials comparing a standard of care to a new treatment option,” said Dr. Lowell E. Schnipper, chair of ASCO’s Value in Cancer Care Task Force.

“I want to be clear: this is not a way of ranking drugs; this is simply a way of understanding the outcome of a clinical trial,” he said at the briefing.

The frameworks use a scoring system to award or subtract points to a specific therapy based on clinical benefit and toxicity, with the two scores combined to generate a Net Health Benefit score that will then be compared with the direct cost of the treatment.

Clinical benefit

For the adjuvant framework, a score of 1-5 for overall survival (OS) will be assigned based on the hazard ratio when the treatment is compared to the standard of care. If the trial does not report OS data, the hazard ratio for disease-free survival (DFS) will be used instead. The categorical score is multiplied, or weighted, by a factor of 16 for OS and 15 for DFS. In this and in the advanced disease framework, the maximum weight of the benefit on survival will be 80 points (16 x 5).

In the advanced/metastatic framework, clinical benefit will be scored based on fractional improvement in median OS over the standard of a care for a specific clinical scenario. As with the adjuvant framework, OS is considered first, DFS if OS is not available, and if neither is available (for example, in a single-arm trial), response rate will be used. In this framework, OS is weighted by a factor of 16, PFS by 11 “because it is a less clinically meaningful end point and is not always a surrogate for OS,” the framework creators note. Response rate will be weighted by 8, an acknowledgment that clinical responses do not always translate into improvements in OS.

In both frameworks, toxicities will be determined relative to the comparator regimen or drug, with a categorical value ranging from –20 (for substantially less well tolerated) to +20 (substantially better).

For the advanced/metastatic disease framework, a treatment or regimen can earn “bonus” points if it can be demonstrated to provide a statistically significant improvement in either palliation of symptoms and/or treatment-free intervals, compared with the control treatment in a prospective clinical trial.

Scores and cost

The Net Health Benefit score will be derived from the combination of the clinical benefit and toxicity score, plus points for regimens designed to treat advanced cancer. The maximum achievable scores are 100 for adjuvant therapies and 130 for advanced/metastatic therapies.

Cost estimates included in the valuation process will include both drug acquisition costs and costs to patients.

ASCO is inviting comments via an online survey through August 21, 2015.