Sara Freeman

MANCHESTER, ENGLAND – Men over the age of 60 years have the highest incidence of malignant melanoma, European data have highlighted.

In the Netherlands, almost 40% of men and 30% of women with newly diagnosed melanoma are over 60 years old, said Dr. Maryska Janssen-Heijnen of VieCuri Medical Centre in Venlo, the Netherlands.

"Future screening campaigns should focus on the elderly, and especially elderly men, because we have seen a very strong increase in incidence," she said at the annual meeting of the International Society of Geriatric Oncology.

A similar situation exists in England, with 30 years’ worth of data from the Office for National Statistics showing a greater proportion of melanoma being diagnosed in people over age 70.

"Older patients tend to present with worse prognostic features – ulceration, high mitotic rate, thicker melanomas, and head and neck distribution being more likely," said Dr. Alistair Ring of Brighton and Sussex Medical School, Brighton, England.

Dr. Ring presented data on all new cases of melanoma reported in England from 1971 to 2010. In 1971, there were 1,094 malignant melanoma registrations – 32% were in men. In 2009, there were 9,771 registrations – 48% were in men.

Looking at incidence by age, the number of registrations in men versus women in 1971 was lower: 33 vs. 64 cases at age 60-64 years, 23 vs. 59 cases at age 65-70, 30 vs. 43 at age 70-74, and 16 vs. 46 at age 75-79 years.

In 2009, however, the number of registrations was higher in men than in women at 60-64 years (637 vs. 592 cases), 65-69 years (580 vs. 460 cases), 70-74 years (562 vs. 429 cases), and 75-79 years (499 vs. 397).

The incidence of melanoma in Holland between 1989 and 2010 was stable for people aged 15-29 years, Dr. Janssen-Heijnen said, with women more likely to be diagnosed than men. The incidence of melanoma has increased among all patients under age 60, but the rate has increased to a greater extent in older patients, particularly in men.

Campaigns to make the public aware about the risk of sun exposure and skin cancer have perhaps helped to encourage screening and reduce melanoma rates in younger people, but the effect appears to have been minimal in the elderly, Dr. Janssen-Heijnen said.

Overall survival also is worse in older than in younger individuals. The poorer survival in elderly might be due to an increased proportion of nodular melanomas in older patients and the development of the disease without early signs and symptoms. Elderly patients also might be less attentive to skin changes and less likely than their younger counterparts to perform self-examinations, she suggested.

The Dutch study found thick (greater than 4 mm) melanomas in 20% of men and 8% of women over age 65 with melanoma. Thick lesions were noted in 16% of men and 5% of women under age 65 with melanoma.

Older patients are also more likely than younger patients to have comorbid conditions, said Dr. Janssen-Heijnen, with 70% of men and 70% of women aged 80 years or older having one or more comorbid conditions at diagnosis of melanoma, versus 28% of men and 23% of women aged 50–64 years.

Recently published data suggest that patients are more likely to die of comorbidity than of their melanoma (Aust. N. Z. J. Public Health 2012;36:441-5).

Dr. Ring also presented data on 454 patients newly diagnosed with melanoma at his institution between 2001 and 2006; almost half (48%) were aged 60 years or older.

"Older patients were more likely to present with more advanced disease," Dr. Ring said. Indeed, 22% of patients aged over 60 years, versus just 8.5% of patients younger than 60 years, were newly diagnosed with stage IIb or stage III disease (P less than .01).

Dr. Ring noted, however, that 67% of patients aged 60 years or older with stage IIb melanoma had no comorbidities (Charlson Comorbidity Index of 0).

"What is important about [these data] is that we’ve got a lot of [older] people with a high risk of recurrence with potentially a low risk of dying from other causes," he commented.

This has implications for enrollment into adjuvant therapy trials, as these patients may represent a population of patients with good potential to respond to recently available targeted agents.

Dr. Janssen-Heijnen and Dr. Ring had no financial disclosures relevant to their presentations.

MANCHESTER, ENGLAND – Men over the age of 60 years have the highest incidence of malignant melanoma, European data have highlighted.

In the Netherlands, almost 40% of men and 30% of women with newly diagnosed melanoma are over 60 years old, said Dr. Maryska Janssen-Heijnen of VieCuri Medical Centre in Venlo, the Netherlands.

"Future screening campaigns should focus on the elderly, and especially elderly men, because we have seen a very strong increase in incidence," she said at the annual meeting of the International Society of Geriatric Oncology.

A similar situation exists in England, with 30 years’ worth of data from the Office for National Statistics showing a greater proportion of melanoma being diagnosed in people over age 70.

"Older patients tend to present with worse prognostic features – ulceration, high mitotic rate, thicker melanomas, and head and neck distribution being more likely," said Dr. Alistair Ring of Brighton and Sussex Medical School, Brighton, England.

Dr. Ring presented data on all new cases of melanoma reported in England from 1971 to 2010. In 1971, there were 1,094 malignant melanoma registrations – 32% were in men. In 2009, there were 9,771 registrations – 48% were in men.

Looking at incidence by age, the number of registrations in men versus women in 1971 was lower: 33 vs. 64 cases at age 60-64 years, 23 vs. 59 cases at age 65-70, 30 vs. 43 at age 70-74, and 16 vs. 46 at age 75-79 years.

In 2009, however, the number of registrations was higher in men than in women at 60-64 years (637 vs. 592 cases), 65-69 years (580 vs. 460 cases), 70-74 years (562 vs. 429 cases), and 75-79 years (499 vs. 397).

The incidence of melanoma in Holland between 1989 and 2010 was stable for people aged 15-29 years, Dr. Janssen-Heijnen said, with women more likely to be diagnosed than men. The incidence of melanoma has increased among all patients under age 60, but the rate has increased to a greater extent in older patients, particularly in men.

Campaigns to make the public aware about the risk of sun exposure and skin cancer have perhaps helped to encourage screening and reduce melanoma rates in younger people, but the effect appears to have been minimal in the elderly, Dr. Janssen-Heijnen said.

Overall survival also is worse in older than in younger individuals. The poorer survival in elderly might be due to an increased proportion of nodular melanomas in older patients and the development of the disease without early signs and symptoms. Elderly patients also might be less attentive to skin changes and less likely than their younger counterparts to perform self-examinations, she suggested.

The Dutch study found thick (greater than 4 mm) melanomas in 20% of men and 8% of women over age 65 with melanoma. Thick lesions were noted in 16% of men and 5% of women under age 65 with melanoma.

Older patients are also more likely than younger patients to have comorbid conditions, said Dr. Janssen-Heijnen, with 70% of men and 70% of women aged 80 years or older having one or more comorbid conditions at diagnosis of melanoma, versus 28% of men and 23% of women aged 50–64 years.

Recently published data suggest that patients are more likely to die of comorbidity than of their melanoma (Aust. N. Z. J. Public Health 2012;36:441-5).

Dr. Ring also presented data on 454 patients newly diagnosed with melanoma at his institution between 2001 and 2006; almost half (48%) were aged 60 years or older.

"Older patients were more likely to present with more advanced disease," Dr. Ring said. Indeed, 22% of patients aged over 60 years, versus just 8.5% of patients younger than 60 years, were newly diagnosed with stage IIb or stage III disease (P less than .01).

Dr. Ring noted, however, that 67% of patients aged 60 years or older with stage IIb melanoma had no comorbidities (Charlson Comorbidity Index of 0).

"What is important about [these data] is that we’ve got a lot of [older] people with a high risk of recurrence with potentially a low risk of dying from other causes," he commented.

This has implications for enrollment into adjuvant therapy trials, as these patients may represent a population of patients with good potential to respond to recently available targeted agents.

Dr. Janssen-Heijnen and Dr. Ring had no financial disclosures relevant to their presentations.

MANCHESTER, ENGLAND – Men over the age of 60 years have the highest incidence of malignant melanoma, European data have highlighted.

In the Netherlands, almost 40% of men and 30% of women with newly diagnosed melanoma are over 60 years old, said Dr. Maryska Janssen-Heijnen of VieCuri Medical Centre in Venlo, the Netherlands.

"Future screening campaigns should focus on the elderly, and especially elderly men, because we have seen a very strong increase in incidence," she said at the annual meeting of the International Society of Geriatric Oncology.

A similar situation exists in England, with 30 years’ worth of data from the Office for National Statistics showing a greater proportion of melanoma being diagnosed in people over age 70.

"Older patients tend to present with worse prognostic features – ulceration, high mitotic rate, thicker melanomas, and head and neck distribution being more likely," said Dr. Alistair Ring of Brighton and Sussex Medical School, Brighton, England.

Dr. Ring presented data on all new cases of melanoma reported in England from 1971 to 2010. In 1971, there were 1,094 malignant melanoma registrations – 32% were in men. In 2009, there were 9,771 registrations – 48% were in men.

Looking at incidence by age, the number of registrations in men versus women in 1971 was lower: 33 vs. 64 cases at age 60-64 years, 23 vs. 59 cases at age 65-70, 30 vs. 43 at age 70-74, and 16 vs. 46 at age 75-79 years.

In 2009, however, the number of registrations was higher in men than in women at 60-64 years (637 vs. 592 cases), 65-69 years (580 vs. 460 cases), 70-74 years (562 vs. 429 cases), and 75-79 years (499 vs. 397).

The incidence of melanoma in Holland between 1989 and 2010 was stable for people aged 15-29 years, Dr. Janssen-Heijnen said, with women more likely to be diagnosed than men. The incidence of melanoma has increased among all patients under age 60, but the rate has increased to a greater extent in older patients, particularly in men.

Campaigns to make the public aware about the risk of sun exposure and skin cancer have perhaps helped to encourage screening and reduce melanoma rates in younger people, but the effect appears to have been minimal in the elderly, Dr. Janssen-Heijnen said.

Overall survival also is worse in older than in younger individuals. The poorer survival in elderly might be due to an increased proportion of nodular melanomas in older patients and the development of the disease without early signs and symptoms. Elderly patients also might be less attentive to skin changes and less likely than their younger counterparts to perform self-examinations, she suggested.

The Dutch study found thick (greater than 4 mm) melanomas in 20% of men and 8% of women over age 65 with melanoma. Thick lesions were noted in 16% of men and 5% of women under age 65 with melanoma.

Older patients are also more likely than younger patients to have comorbid conditions, said Dr. Janssen-Heijnen, with 70% of men and 70% of women aged 80 years or older having one or more comorbid conditions at diagnosis of melanoma, versus 28% of men and 23% of women aged 50–64 years.

Recently published data suggest that patients are more likely to die of comorbidity than of their melanoma (Aust. N. Z. J. Public Health 2012;36:441-5).

Dr. Ring also presented data on 454 patients newly diagnosed with melanoma at his institution between 2001 and 2006; almost half (48%) were aged 60 years or older.

"Older patients were more likely to present with more advanced disease," Dr. Ring said. Indeed, 22% of patients aged over 60 years, versus just 8.5% of patients younger than 60 years, were newly diagnosed with stage IIb or stage III disease (P less than .01).

Dr. Ring noted, however, that 67% of patients aged 60 years or older with stage IIb melanoma had no comorbidities (Charlson Comorbidity Index of 0).

"What is important about [these data] is that we’ve got a lot of [older] people with a high risk of recurrence with potentially a low risk of dying from other causes," he commented.

This has implications for enrollment into adjuvant therapy trials, as these patients may represent a population of patients with good potential to respond to recently available targeted agents.

Dr. Janssen-Heijnen and Dr. Ring had no financial disclosures relevant to their presentations.

MANCHESTER, ENGLAND – Elderly cancer patients need to be screened for malnutrition, and individualized, multimodal interventions should be used in those found to require nourishment, according to the chair of a task force on nutrition in geriatric oncology.

"Nutrition is important in [elderly] cancer patients, yet still many oncologists neglect this aspect [of treatment]," the chair, Dr. Federico Bozzetti, told attendees during a special session on nutritional issues at the annual meeting of the International Society of Geriatric Oncology.

Standing in the way is a paucity of randomized clinical trials demonstrating the efficacy of nutritional support in cancer patients, and notably in those who are elderly, acknowledged Dr. Bozzetti, a surgical oncologist from the University of Milan.

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Evidence links malnutrition to worse clinical outcomes, increased hospital stays, a longer duration of convalescence, reduced quality of life, increased morbidity, and increased mortality in the general patient population, however (Clin. Nutr. 2008;27:340-9; Eur. J. Clin. Nutr. 2007;62:687-94; Br. J. Nutr. 2004; 92:105-11; Am. J. Clin. Nutr. 1997;66:1232), Dr. Bozzetti noted.

"Old people, regardless of whether they are healthy or ill, need to be nourished," he said.

The International Society of Geriatric Oncology (SIOG) Task Force on Nutrition has as its initial aim development of a consensus-based report to provide practical guidance on nutritional support. The report is due for publication early next year.

Nutritional support currently falls "somewhere between medicine and supportive care," Dr. Bozzetti suggested, adding that beneficial effects are more likely to be seen in patients who are severely malnourished than in those who are mildly malnourished.

How Can You Screen For Malnutrition?

"Malnutrition is a subacute or chronic state of nutrition," said Dr. Zeno Stanga of University Hospital Bern (Switzerland), citing the European Society for Clinical Nutrition and Metabolism definition. It is a state "in which a combination of varying degrees of over- or undernutrition and inflammatory activity have led to a change in body composition and diminished function," he added.

Data suggest that up to 56% of geriatric patients are malnourished (Clin. Nutr. 2006;25:563-72), he noted, with around 20%-80% of cancer patients at severe nutritional risk.

"All cancer patients must receive a nutritional screening at presentation," Dr. Stanga proposed. This should be performed in order to plan adequate nutritional therapy, with interventions tailored to the individual’s needs and revised often.

Nutritional status can be influenced by a variety of factors, with food intake, body mass index, pathologic weight loss, and the severity of disease being the four key ones to assess. Measuring a single parameter is not enough, he said, and there are several screening tools that may help to identify if a patient is at risk of malnutrition and requires nutritional support.

Although there is no consensus on which tool is best for nutritional screening, the options include the Malnutritional Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS) 2002, and the Mini Nutritional Assessment Short Form (MNA-SF).

What is important, Dr. Stanga maintained, is that a screening protocol be implemented at institutions using a validated tool, and that patients be given appropriate action plans as a result.

What Type of Nutritional Support?

Adjuvant nutrition can play an important role in the management of cancer patients, said Dr. Paula Ravasco of the University of Lisbon.

"The evidence today argues for the integration of both early and individualized nutritional counseling as adjuvant therapy," said Dr. Ravasco, a member of the SIOG Task Force on Nutrition.

Dr. Ravasco has previously reported the findings of one of the few randomized controlled trials in this area (Am. J. Clin. Nutr. 2012 Nov. 7 [doi: 10.3945/ajcn.111.018838]), showing that individualized nutritional counseling with regular foods is of benefit in patients with colorectal cancer treated with radiotherapy. Patients who underwent nutritional counseling had improved nutritional intake and status, reduced toxicity, and improved quality of life compared with patients who received no counseling.

The evidence-based dietary intervention used at her institution involves counseling and using prescribed therapeutic diets that are modified to fulfill the specific requirement of patients. "We perhaps have to maintain, as far as possible, the usual dietary pattern that the patient usually has," Dr. Ravasco said.

On the topic of tailoring nutritional support, Dr. Bozzetti noted that patients with a functioning gastrointestinal (GI) tract might respond to counseling and the use of oral dietary supplements or stimulants. "These have the potential to be used in a very large number of patients," he said.

Nasogastric or nasojejunal tube feeding might be the best option for short-term nutritional support if the upper GI tract is not working, he suggested. Percutaneous gastrostomy may be needed for long-term support. Parenteral nutrition may be used on its own in those with a nonfunctioning GI tract, or as a practical way to supplement inadequate oral nutrition, Dr. Bozzetti said.

The session on nutritional issues in elderly cancer patients was partially supported by an unrestricted educational grant from Abbott Nutrition. Dr. Bozzetti, Dr. Ravasco, and Dr. Stanga did not make any disclosures about potential conflicts of interest.

MANCHESTER, ENGLAND – Elderly cancer patients need to be screened for malnutrition, and individualized, multimodal interventions should be used in those found to require nourishment, according to the chair of a task force on nutrition in geriatric oncology.

"Nutrition is important in [elderly] cancer patients, yet still many oncologists neglect this aspect [of treatment]," the chair, Dr. Federico Bozzetti, told attendees during a special session on nutritional issues at the annual meeting of the International Society of Geriatric Oncology.

Standing in the way is a paucity of randomized clinical trials demonstrating the efficacy of nutritional support in cancer patients, and notably in those who are elderly, acknowledged Dr. Bozzetti, a surgical oncologist from the University of Milan.

www.thinkstockphotos.com

Evidence links malnutrition to worse clinical outcomes, increased hospital stays, a longer duration of convalescence, reduced quality of life, increased morbidity, and increased mortality in the general patient population, however (Clin. Nutr. 2008;27:340-9; Eur. J. Clin. Nutr. 2007;62:687-94; Br. J. Nutr. 2004; 92:105-11; Am. J. Clin. Nutr. 1997;66:1232), Dr. Bozzetti noted.

"Old people, regardless of whether they are healthy or ill, need to be nourished," he said.

The International Society of Geriatric Oncology (SIOG) Task Force on Nutrition has as its initial aim development of a consensus-based report to provide practical guidance on nutritional support. The report is due for publication early next year.

Nutritional support currently falls "somewhere between medicine and supportive care," Dr. Bozzetti suggested, adding that beneficial effects are more likely to be seen in patients who are severely malnourished than in those who are mildly malnourished.

How Can You Screen For Malnutrition?

"Malnutrition is a subacute or chronic state of nutrition," said Dr. Zeno Stanga of University Hospital Bern (Switzerland), citing the European Society for Clinical Nutrition and Metabolism definition. It is a state "in which a combination of varying degrees of over- or undernutrition and inflammatory activity have led to a change in body composition and diminished function," he added.

Data suggest that up to 56% of geriatric patients are malnourished (Clin. Nutr. 2006;25:563-72), he noted, with around 20%-80% of cancer patients at severe nutritional risk.

"All cancer patients must receive a nutritional screening at presentation," Dr. Stanga proposed. This should be performed in order to plan adequate nutritional therapy, with interventions tailored to the individual’s needs and revised often.

Nutritional status can be influenced by a variety of factors, with food intake, body mass index, pathologic weight loss, and the severity of disease being the four key ones to assess. Measuring a single parameter is not enough, he said, and there are several screening tools that may help to identify if a patient is at risk of malnutrition and requires nutritional support.

Although there is no consensus on which tool is best for nutritional screening, the options include the Malnutritional Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS) 2002, and the Mini Nutritional Assessment Short Form (MNA-SF).

What is important, Dr. Stanga maintained, is that a screening protocol be implemented at institutions using a validated tool, and that patients be given appropriate action plans as a result.

What Type of Nutritional Support?

Adjuvant nutrition can play an important role in the management of cancer patients, said Dr. Paula Ravasco of the University of Lisbon.

"The evidence today argues for the integration of both early and individualized nutritional counseling as adjuvant therapy," said Dr. Ravasco, a member of the SIOG Task Force on Nutrition.

Dr. Ravasco has previously reported the findings of one of the few randomized controlled trials in this area (Am. J. Clin. Nutr. 2012 Nov. 7 [doi: 10.3945/ajcn.111.018838]), showing that individualized nutritional counseling with regular foods is of benefit in patients with colorectal cancer treated with radiotherapy. Patients who underwent nutritional counseling had improved nutritional intake and status, reduced toxicity, and improved quality of life compared with patients who received no counseling.

The evidence-based dietary intervention used at her institution involves counseling and using prescribed therapeutic diets that are modified to fulfill the specific requirement of patients. "We perhaps have to maintain, as far as possible, the usual dietary pattern that the patient usually has," Dr. Ravasco said.

On the topic of tailoring nutritional support, Dr. Bozzetti noted that patients with a functioning gastrointestinal (GI) tract might respond to counseling and the use of oral dietary supplements or stimulants. "These have the potential to be used in a very large number of patients," he said.

Nasogastric or nasojejunal tube feeding might be the best option for short-term nutritional support if the upper GI tract is not working, he suggested. Percutaneous gastrostomy may be needed for long-term support. Parenteral nutrition may be used on its own in those with a nonfunctioning GI tract, or as a practical way to supplement inadequate oral nutrition, Dr. Bozzetti said.

The session on nutritional issues in elderly cancer patients was partially supported by an unrestricted educational grant from Abbott Nutrition. Dr. Bozzetti, Dr. Ravasco, and Dr. Stanga did not make any disclosures about potential conflicts of interest.

MANCHESTER, ENGLAND – Elderly cancer patients need to be screened for malnutrition, and individualized, multimodal interventions should be used in those found to require nourishment, according to the chair of a task force on nutrition in geriatric oncology.

"Nutrition is important in [elderly] cancer patients, yet still many oncologists neglect this aspect [of treatment]," the chair, Dr. Federico Bozzetti, told attendees during a special session on nutritional issues at the annual meeting of the International Society of Geriatric Oncology.

Standing in the way is a paucity of randomized clinical trials demonstrating the efficacy of nutritional support in cancer patients, and notably in those who are elderly, acknowledged Dr. Bozzetti, a surgical oncologist from the University of Milan.

www.thinkstockphotos.com

Evidence links malnutrition to worse clinical outcomes, increased hospital stays, a longer duration of convalescence, reduced quality of life, increased morbidity, and increased mortality in the general patient population, however (Clin. Nutr. 2008;27:340-9; Eur. J. Clin. Nutr. 2007;62:687-94; Br. J. Nutr. 2004; 92:105-11; Am. J. Clin. Nutr. 1997;66:1232), Dr. Bozzetti noted.

"Old people, regardless of whether they are healthy or ill, need to be nourished," he said.

The International Society of Geriatric Oncology (SIOG) Task Force on Nutrition has as its initial aim development of a consensus-based report to provide practical guidance on nutritional support. The report is due for publication early next year.

Nutritional support currently falls "somewhere between medicine and supportive care," Dr. Bozzetti suggested, adding that beneficial effects are more likely to be seen in patients who are severely malnourished than in those who are mildly malnourished.

How Can You Screen For Malnutrition?

"Malnutrition is a subacute or chronic state of nutrition," said Dr. Zeno Stanga of University Hospital Bern (Switzerland), citing the European Society for Clinical Nutrition and Metabolism definition. It is a state "in which a combination of varying degrees of over- or undernutrition and inflammatory activity have led to a change in body composition and diminished function," he added.

Data suggest that up to 56% of geriatric patients are malnourished (Clin. Nutr. 2006;25:563-72), he noted, with around 20%-80% of cancer patients at severe nutritional risk.

"All cancer patients must receive a nutritional screening at presentation," Dr. Stanga proposed. This should be performed in order to plan adequate nutritional therapy, with interventions tailored to the individual’s needs and revised often.

Nutritional status can be influenced by a variety of factors, with food intake, body mass index, pathologic weight loss, and the severity of disease being the four key ones to assess. Measuring a single parameter is not enough, he said, and there are several screening tools that may help to identify if a patient is at risk of malnutrition and requires nutritional support.

Although there is no consensus on which tool is best for nutritional screening, the options include the Malnutritional Universal Screening Tool (MUST), the Nutritional Risk Screening (NRS) 2002, and the Mini Nutritional Assessment Short Form (MNA-SF).

What is important, Dr. Stanga maintained, is that a screening protocol be implemented at institutions using a validated tool, and that patients be given appropriate action plans as a result.

What Type of Nutritional Support?

Adjuvant nutrition can play an important role in the management of cancer patients, said Dr. Paula Ravasco of the University of Lisbon.

"The evidence today argues for the integration of both early and individualized nutritional counseling as adjuvant therapy," said Dr. Ravasco, a member of the SIOG Task Force on Nutrition.

Dr. Ravasco has previously reported the findings of one of the few randomized controlled trials in this area (Am. J. Clin. Nutr. 2012 Nov. 7 [doi: 10.3945/ajcn.111.018838]), showing that individualized nutritional counseling with regular foods is of benefit in patients with colorectal cancer treated with radiotherapy. Patients who underwent nutritional counseling had improved nutritional intake and status, reduced toxicity, and improved quality of life compared with patients who received no counseling.

The evidence-based dietary intervention used at her institution involves counseling and using prescribed therapeutic diets that are modified to fulfill the specific requirement of patients. "We perhaps have to maintain, as far as possible, the usual dietary pattern that the patient usually has," Dr. Ravasco said.

On the topic of tailoring nutritional support, Dr. Bozzetti noted that patients with a functioning gastrointestinal (GI) tract might respond to counseling and the use of oral dietary supplements or stimulants. "These have the potential to be used in a very large number of patients," he said.

Nasogastric or nasojejunal tube feeding might be the best option for short-term nutritional support if the upper GI tract is not working, he suggested. Percutaneous gastrostomy may be needed for long-term support. Parenteral nutrition may be used on its own in those with a nonfunctioning GI tract, or as a practical way to supplement inadequate oral nutrition, Dr. Bozzetti said.

The session on nutritional issues in elderly cancer patients was partially supported by an unrestricted educational grant from Abbott Nutrition. Dr. Bozzetti, Dr. Ravasco, and Dr. Stanga did not make any disclosures about potential conflicts of interest.

MANCHESTER, ENGLAND – Undertaking a few simple baseline assessments in elderly patients may help predict their risk of worsening physical function and falls occurring 2-3 months into cancer therapy, a prospective, multicenter study has shown.

Nearly a fifth (17.2%) of 811 patients in the analysis experienced a worsening in Activities of Daily Living (ADL) during treatment. Instrumental Activities of Daily Living (IADL) scores decreased in 38.9%, and 17.5% had at least one fall.

"Parameters from the CGA [Comprehensive Geriatric Assessment] before treatment in older cancer patients can identify at-risk patients for decline in functionality and development of falls," Cindy Kenis, R.N., of the University Hospitals Leuven (Belgium), annual meeting of the International Society of Geriatric Oncology (SIOG).

This emphasizes the need to "make sure that we foresee the necessary support for older cancer patients based on the results of a geriatric screening and evaluation for the different geriatric problems detected," Ms. Kenis added later in an interview.

A total of 937 patients aged 70 years or older were included in the study. The median age was 76 years, and 63.5% of the study population were female. The most common malignancy was breast cancer (40.4%); other malignancies included colon cancer (20.6%), hematologic malignancies (15.9%), prostate cancer (9%), lung cancer (7.8%), and ovarian cancer (6.3%).

Several geriatric assessment tools were used at baseline, including the G8 and the Flemish Triage Risk Screening Tool (TRST), followed by a Comprehensive Geriatric Assessment (CGA).

Follow-up assessments after 2-3 months’ cancer treatment were ADL, IADL, the number of falls, and chemotherapy toxicity. A decline in functionality occurred if there was a worsening of ADL by 2 or more points and IADL by 1 or more points, or if the patient had a fall.

Worsening ADL could be predicted by baseline scores in three measures: IADL, a mininutritional assessment (MNA), and the Flemish TRST (all P less than .05).

Patients classified as "dependent" on IADL at baseline (a score less than 8 for women and less than 5 for men) were almost twice as likely to have worsening ADL at any time point during follow-up as were those not seen as dependent on IADL at baseline (odds ratio, 0.54).

Patients at risk for malnutrition or malnourishment (a score less than 24 on MNA) also had about twice the risk of decline in ADL at the time point of follow-up as did those who had higher MNA scores (OR, 0.51).

Furthermore, patients classified as having a geriatric risk profile (a Flemish TRST score of 1 or higher) also had about twice the risk of ADL decline at follow-up as did those not having a geriatric risk profile (OR, 0.48).

Worsening IADL was predicted by baseline ECOG performance status (PS), Geriatric Depression Scale (GDS)–15 scores, and having chemotherapy (all P less than .05).

Patients with a PS of 0 or 1 at baseline were twice as likely to experience a decline in IADL as were those with worse PS (OR, 2.00). "This sounds somewhat contradictory," Ms. Kenis acknowledged, "but [it] can be explained by the fact that patients who already scored 2 or more on ECOG baseline, couldn’t get much worse," she explained.

Patients with a geriatric risk profile in need of further in-depth CGA (a Flemish TRST score of 1 or greater) had about twice the risk of IADL decline than as did those without such a profile (OR, 0.52).

Patients at risk for depression (a GDS-15 score less than 5) had about a third more risk of a decline in IADL as did those not at risk for depression (OR, 0.58).

Patients who had received any type of chemotherapy were also more likely to experience a decline in IADL (OR, 0.62).

Prior falls, baseline ADL, G8 assessment, living situation, and the disease setting (new diagnosis or cancer progression) were predictive of a future fall (all P less than .05):

• Patients who had already experienced a fall in the year before study inclusion were almost four times more likely to have another fall during follow-up than those who had not had a prior fall the year before (OR, .62).

• Patients classified as dependent on ADL at baseline (Belgian Katz scale score greater than 6) had about three times more risk of new falls. (OR, 0.42).

• Patients in need of further in-depth CGA (G8 score up to 14) had about four times more risk of new falls (OR, 0.38).

• Living alone was also predictive, almost doubling the risk of a fall (OR, 0.63).

• Patients who were included in the study at disease progression were 1.5 times more likely to experience a new fall than were people whose disease had just been diagnosed (OR, 0.58). "This can be explained by the fact that [these] patients were often in a less-good condition than patients [with a] new diagnosis," Ms. Kenis said.

"It is not only the goal to detect problems in a two-step approach (geriatric screening and, if necessary, a full CGA), but [also] to reach the three-step approach (geriatric screening and, if necessary, a full CGA, followed by concrete geriatric advice and interventions)," Ms Kenis said in an interview.

She added: "One of the main goals for the future is to see what the impact is of the implementation of geriatric advice and interventions on functionality and falls in older cancer patients."

The study was supported by Vlaamse Liga tegen Kanker. Ms. Kenis said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Undertaking a few simple baseline assessments in elderly patients may help predict their risk of worsening physical function and falls occurring 2-3 months into cancer therapy, a prospective, multicenter study has shown.

Nearly a fifth (17.2%) of 811 patients in the analysis experienced a worsening in Activities of Daily Living (ADL) during treatment. Instrumental Activities of Daily Living (IADL) scores decreased in 38.9%, and 17.5% had at least one fall.

"Parameters from the CGA [Comprehensive Geriatric Assessment] before treatment in older cancer patients can identify at-risk patients for decline in functionality and development of falls," Cindy Kenis, R.N., of the University Hospitals Leuven (Belgium), annual meeting of the International Society of Geriatric Oncology (SIOG).

This emphasizes the need to "make sure that we foresee the necessary support for older cancer patients based on the results of a geriatric screening and evaluation for the different geriatric problems detected," Ms. Kenis added later in an interview.

A total of 937 patients aged 70 years or older were included in the study. The median age was 76 years, and 63.5% of the study population were female. The most common malignancy was breast cancer (40.4%); other malignancies included colon cancer (20.6%), hematologic malignancies (15.9%), prostate cancer (9%), lung cancer (7.8%), and ovarian cancer (6.3%).

Several geriatric assessment tools were used at baseline, including the G8 and the Flemish Triage Risk Screening Tool (TRST), followed by a Comprehensive Geriatric Assessment (CGA).

Follow-up assessments after 2-3 months’ cancer treatment were ADL, IADL, the number of falls, and chemotherapy toxicity. A decline in functionality occurred if there was a worsening of ADL by 2 or more points and IADL by 1 or more points, or if the patient had a fall.

Worsening ADL could be predicted by baseline scores in three measures: IADL, a mininutritional assessment (MNA), and the Flemish TRST (all P less than .05).

Patients classified as "dependent" on IADL at baseline (a score less than 8 for women and less than 5 for men) were almost twice as likely to have worsening ADL at any time point during follow-up as were those not seen as dependent on IADL at baseline (odds ratio, 0.54).

Patients at risk for malnutrition or malnourishment (a score less than 24 on MNA) also had about twice the risk of decline in ADL at the time point of follow-up as did those who had higher MNA scores (OR, 0.51).

Furthermore, patients classified as having a geriatric risk profile (a Flemish TRST score of 1 or higher) also had about twice the risk of ADL decline at follow-up as did those not having a geriatric risk profile (OR, 0.48).

Worsening IADL was predicted by baseline ECOG performance status (PS), Geriatric Depression Scale (GDS)–15 scores, and having chemotherapy (all P less than .05).

Patients with a PS of 0 or 1 at baseline were twice as likely to experience a decline in IADL as were those with worse PS (OR, 2.00). "This sounds somewhat contradictory," Ms. Kenis acknowledged, "but [it] can be explained by the fact that patients who already scored 2 or more on ECOG baseline, couldn’t get much worse," she explained.

Patients with a geriatric risk profile in need of further in-depth CGA (a Flemish TRST score of 1 or greater) had about twice the risk of IADL decline than as did those without such a profile (OR, 0.52).

Patients at risk for depression (a GDS-15 score less than 5) had about a third more risk of a decline in IADL as did those not at risk for depression (OR, 0.58).

Patients who had received any type of chemotherapy were also more likely to experience a decline in IADL (OR, 0.62).

Prior falls, baseline ADL, G8 assessment, living situation, and the disease setting (new diagnosis or cancer progression) were predictive of a future fall (all P less than .05):

• Patients who had already experienced a fall in the year before study inclusion were almost four times more likely to have another fall during follow-up than those who had not had a prior fall the year before (OR, .62).

• Patients classified as dependent on ADL at baseline (Belgian Katz scale score greater than 6) had about three times more risk of new falls. (OR, 0.42).

• Patients in need of further in-depth CGA (G8 score up to 14) had about four times more risk of new falls (OR, 0.38).

• Living alone was also predictive, almost doubling the risk of a fall (OR, 0.63).

• Patients who were included in the study at disease progression were 1.5 times more likely to experience a new fall than were people whose disease had just been diagnosed (OR, 0.58). "This can be explained by the fact that [these] patients were often in a less-good condition than patients [with a] new diagnosis," Ms. Kenis said.

"It is not only the goal to detect problems in a two-step approach (geriatric screening and, if necessary, a full CGA), but [also] to reach the three-step approach (geriatric screening and, if necessary, a full CGA, followed by concrete geriatric advice and interventions)," Ms Kenis said in an interview.

She added: "One of the main goals for the future is to see what the impact is of the implementation of geriatric advice and interventions on functionality and falls in older cancer patients."

The study was supported by Vlaamse Liga tegen Kanker. Ms. Kenis said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Undertaking a few simple baseline assessments in elderly patients may help predict their risk of worsening physical function and falls occurring 2-3 months into cancer therapy, a prospective, multicenter study has shown.

Nearly a fifth (17.2%) of 811 patients in the analysis experienced a worsening in Activities of Daily Living (ADL) during treatment. Instrumental Activities of Daily Living (IADL) scores decreased in 38.9%, and 17.5% had at least one fall.

"Parameters from the CGA [Comprehensive Geriatric Assessment] before treatment in older cancer patients can identify at-risk patients for decline in functionality and development of falls," Cindy Kenis, R.N., of the University Hospitals Leuven (Belgium), annual meeting of the International Society of Geriatric Oncology (SIOG).

This emphasizes the need to "make sure that we foresee the necessary support for older cancer patients based on the results of a geriatric screening and evaluation for the different geriatric problems detected," Ms. Kenis added later in an interview.

A total of 937 patients aged 70 years or older were included in the study. The median age was 76 years, and 63.5% of the study population were female. The most common malignancy was breast cancer (40.4%); other malignancies included colon cancer (20.6%), hematologic malignancies (15.9%), prostate cancer (9%), lung cancer (7.8%), and ovarian cancer (6.3%).

Several geriatric assessment tools were used at baseline, including the G8 and the Flemish Triage Risk Screening Tool (TRST), followed by a Comprehensive Geriatric Assessment (CGA).

Follow-up assessments after 2-3 months’ cancer treatment were ADL, IADL, the number of falls, and chemotherapy toxicity. A decline in functionality occurred if there was a worsening of ADL by 2 or more points and IADL by 1 or more points, or if the patient had a fall.

Worsening ADL could be predicted by baseline scores in three measures: IADL, a mininutritional assessment (MNA), and the Flemish TRST (all P less than .05).

Patients classified as "dependent" on IADL at baseline (a score less than 8 for women and less than 5 for men) were almost twice as likely to have worsening ADL at any time point during follow-up as were those not seen as dependent on IADL at baseline (odds ratio, 0.54).

Patients at risk for malnutrition or malnourishment (a score less than 24 on MNA) also had about twice the risk of decline in ADL at the time point of follow-up as did those who had higher MNA scores (OR, 0.51).

Furthermore, patients classified as having a geriatric risk profile (a Flemish TRST score of 1 or higher) also had about twice the risk of ADL decline at follow-up as did those not having a geriatric risk profile (OR, 0.48).

Worsening IADL was predicted by baseline ECOG performance status (PS), Geriatric Depression Scale (GDS)–15 scores, and having chemotherapy (all P less than .05).

Patients with a PS of 0 or 1 at baseline were twice as likely to experience a decline in IADL as were those with worse PS (OR, 2.00). "This sounds somewhat contradictory," Ms. Kenis acknowledged, "but [it] can be explained by the fact that patients who already scored 2 or more on ECOG baseline, couldn’t get much worse," she explained.

Patients with a geriatric risk profile in need of further in-depth CGA (a Flemish TRST score of 1 or greater) had about twice the risk of IADL decline than as did those without such a profile (OR, 0.52).

Patients at risk for depression (a GDS-15 score less than 5) had about a third more risk of a decline in IADL as did those not at risk for depression (OR, 0.58).

Patients who had received any type of chemotherapy were also more likely to experience a decline in IADL (OR, 0.62).

Prior falls, baseline ADL, G8 assessment, living situation, and the disease setting (new diagnosis or cancer progression) were predictive of a future fall (all P less than .05):

• Patients who had already experienced a fall in the year before study inclusion were almost four times more likely to have another fall during follow-up than those who had not had a prior fall the year before (OR, .62).

• Patients classified as dependent on ADL at baseline (Belgian Katz scale score greater than 6) had about three times more risk of new falls. (OR, 0.42).

• Patients in need of further in-depth CGA (G8 score up to 14) had about four times more risk of new falls (OR, 0.38).

• Living alone was also predictive, almost doubling the risk of a fall (OR, 0.63).

• Patients who were included in the study at disease progression were 1.5 times more likely to experience a new fall than were people whose disease had just been diagnosed (OR, 0.58). "This can be explained by the fact that [these] patients were often in a less-good condition than patients [with a] new diagnosis," Ms. Kenis said.

"It is not only the goal to detect problems in a two-step approach (geriatric screening and, if necessary, a full CGA), but [also] to reach the three-step approach (geriatric screening and, if necessary, a full CGA, followed by concrete geriatric advice and interventions)," Ms Kenis said in an interview.

She added: "One of the main goals for the future is to see what the impact is of the implementation of geriatric advice and interventions on functionality and falls in older cancer patients."

The study was supported by Vlaamse Liga tegen Kanker. Ms. Kenis said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women who are breast cancer survivors have a greater risk of developing additional primary cancers in the long term than those under 65 years of age, according to an analysis of data on more than 100,000 survivors in the United States.

Women aged 70-79 years appear to have the highest risk of developing a multiple primary malignancy (MPM), with a crude 10-year incidence of 17.8/10,000 person-years. In comparisons, the rate of risk for survivors younger than 65 was 11.7, increasing to 16.7 for those 65-69 years of age and 16.4 for those 80 years and older.

Other common cancers occurring in the breast cancer survivor population were lung and colon cancers, investigator Kerri Clough-Gorr, D.Sc., reported at the annual meeting of the International Society of Geriatric Oncology. Hematologic malignancies, melanoma, and urinary and digestive tumors were also observed.

"Relative breast cancer survival rates are quite high in the United States, at over 89% at 5 years [after a diagnosis]," said Dr. Clough-Gorr of Boston University and the Institute of Social and Preventative Medicine at the University of Bern (Switzerland).

"Importantly, the vast majority of women with breast cancer become long-term survivors, and they are at risk for developing subsequent malignancies," she added.

It is estimated that there are 2.4 million women in the United States with a history of breast cancer, and the current study aimed to look at survivors’ risk of developing multiple primary cancers over a 20-year follow-up period.

The study analyzed data from 12 SEER (Surveillance, Epidemiology, and End Results) program registry sites on 110,440 women diagnosed with a first primary breast cancer between 1986 and 1994. The women were evaluated for the development of other primary cancers or death up until 2006.

In addition to being more likely to develop another primary cancer, older women were more likely to develop it more quickly. The mean time to develop any MPM was 50 months for women 80-plus years compared with 100 months in those under 65 years. Values for women aged 65-69 and 70-79 were 85 and 72 months.

The stage of the first primary breast cancer at diagnosis did not affect the risk of subsequent MPM, nor were any sociodemographic factors or the year of diagnosis found to be of influence.

"Age was the strongest, significant predictor of multiple primary malignancy risk in this population," Dr. Clough-Gorr noted, adding that the risk was highest in women 70-79 years, with a hazard ratio of 1.48. Hazard ratios for ages 65-69 and 80-plus years were 1.41 and 1.32.

"These findings suggest there are age-related differences in [the] risk of developing an MPM after a primary breast cancer diagnosis," Ms. Clough-Gorr concluded. "In this population, there were no other MPM risk factors that were identified."

The study was supported by the National Cancer Institute. Dr. Clough-Gorr said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women who are breast cancer survivors have a greater risk of developing additional primary cancers in the long term than those under 65 years of age, according to an analysis of data on more than 100,000 survivors in the United States.

Women aged 70-79 years appear to have the highest risk of developing a multiple primary malignancy (MPM), with a crude 10-year incidence of 17.8/10,000 person-years. In comparisons, the rate of risk for survivors younger than 65 was 11.7, increasing to 16.7 for those 65-69 years of age and 16.4 for those 80 years and older.

Other common cancers occurring in the breast cancer survivor population were lung and colon cancers, investigator Kerri Clough-Gorr, D.Sc., reported at the annual meeting of the International Society of Geriatric Oncology. Hematologic malignancies, melanoma, and urinary and digestive tumors were also observed.

"Relative breast cancer survival rates are quite high in the United States, at over 89% at 5 years [after a diagnosis]," said Dr. Clough-Gorr of Boston University and the Institute of Social and Preventative Medicine at the University of Bern (Switzerland).

"Importantly, the vast majority of women with breast cancer become long-term survivors, and they are at risk for developing subsequent malignancies," she added.

It is estimated that there are 2.4 million women in the United States with a history of breast cancer, and the current study aimed to look at survivors’ risk of developing multiple primary cancers over a 20-year follow-up period.

The study analyzed data from 12 SEER (Surveillance, Epidemiology, and End Results) program registry sites on 110,440 women diagnosed with a first primary breast cancer between 1986 and 1994. The women were evaluated for the development of other primary cancers or death up until 2006.

In addition to being more likely to develop another primary cancer, older women were more likely to develop it more quickly. The mean time to develop any MPM was 50 months for women 80-plus years compared with 100 months in those under 65 years. Values for women aged 65-69 and 70-79 were 85 and 72 months.

The stage of the first primary breast cancer at diagnosis did not affect the risk of subsequent MPM, nor were any sociodemographic factors or the year of diagnosis found to be of influence.

"Age was the strongest, significant predictor of multiple primary malignancy risk in this population," Dr. Clough-Gorr noted, adding that the risk was highest in women 70-79 years, with a hazard ratio of 1.48. Hazard ratios for ages 65-69 and 80-plus years were 1.41 and 1.32.

"These findings suggest there are age-related differences in [the] risk of developing an MPM after a primary breast cancer diagnosis," Ms. Clough-Gorr concluded. "In this population, there were no other MPM risk factors that were identified."

The study was supported by the National Cancer Institute. Dr. Clough-Gorr said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women who are breast cancer survivors have a greater risk of developing additional primary cancers in the long term than those under 65 years of age, according to an analysis of data on more than 100,000 survivors in the United States.

Women aged 70-79 years appear to have the highest risk of developing a multiple primary malignancy (MPM), with a crude 10-year incidence of 17.8/10,000 person-years. In comparisons, the rate of risk for survivors younger than 65 was 11.7, increasing to 16.7 for those 65-69 years of age and 16.4 for those 80 years and older.

Other common cancers occurring in the breast cancer survivor population were lung and colon cancers, investigator Kerri Clough-Gorr, D.Sc., reported at the annual meeting of the International Society of Geriatric Oncology. Hematologic malignancies, melanoma, and urinary and digestive tumors were also observed.

"Relative breast cancer survival rates are quite high in the United States, at over 89% at 5 years [after a diagnosis]," said Dr. Clough-Gorr of Boston University and the Institute of Social and Preventative Medicine at the University of Bern (Switzerland).

"Importantly, the vast majority of women with breast cancer become long-term survivors, and they are at risk for developing subsequent malignancies," she added.

It is estimated that there are 2.4 million women in the United States with a history of breast cancer, and the current study aimed to look at survivors’ risk of developing multiple primary cancers over a 20-year follow-up period.

The study analyzed data from 12 SEER (Surveillance, Epidemiology, and End Results) program registry sites on 110,440 women diagnosed with a first primary breast cancer between 1986 and 1994. The women were evaluated for the development of other primary cancers or death up until 2006.

In addition to being more likely to develop another primary cancer, older women were more likely to develop it more quickly. The mean time to develop any MPM was 50 months for women 80-plus years compared with 100 months in those under 65 years. Values for women aged 65-69 and 70-79 were 85 and 72 months.

The stage of the first primary breast cancer at diagnosis did not affect the risk of subsequent MPM, nor were any sociodemographic factors or the year of diagnosis found to be of influence.

"Age was the strongest, significant predictor of multiple primary malignancy risk in this population," Dr. Clough-Gorr noted, adding that the risk was highest in women 70-79 years, with a hazard ratio of 1.48. Hazard ratios for ages 65-69 and 80-plus years were 1.41 and 1.32.

"These findings suggest there are age-related differences in [the] risk of developing an MPM after a primary breast cancer diagnosis," Ms. Clough-Gorr concluded. "In this population, there were no other MPM risk factors that were identified."

The study was supported by the National Cancer Institute. Dr. Clough-Gorr said she had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women with primary, operable, triple-negative breast cancer may have less aggressive tumor biology despite being treated for larger tumors than their younger counterparts, new data suggest.

Tumor samples taken from women aged 70 years or older were found to be of lower grade with significantly lower expression of the tumor markers Ki67 and p53 than seen in younger women, investigators reported at the annual meeting of the International Society of Geriatric Oncology (SIOG).

These data may help explain why similar clinical outcomes were achieved despite aggressive adjuvant chemotherapy not being given to the more elderly women, said investigator Dr. Kwok-Leung Cheung, of the University of Nottingham, England. "The precise place of adjuvant chemotherapy in the treatment of these patients has yet to be defined," he said.

The new report adds to previous findings presented at the American Society of Clinical Oncology (ASCO) meeting in 2011, (J. Clin. Oncol. 2011;29:abstr 1057), Dr. Cheung noted.

At ASCO, Dr. Cheung and his coauthors reported that they had identified 127 older women with triple-negative breast cancer among more than 2,000 women, aged 70 years and older, who had been treated over a 36-year period (1973-2009) for early operable primary breast cancer at a single clinic and also who had good quality tumor samples available for tissue microarray analysis using indirect immunohistochemistry.

The initial study compared this group’s results with those of 342 women with triple-negative breast cancer in a previously characterized consecutive series of 1,809 patients treated at the same clinic from 1986 to 1998. The rates of 5-year breast cancer-specific survival (73% vs. 79%) and of local (10% vs. 14%), regional (11% vs. 14%), and distant (30% vs. 27%) recurrences were found to be similar in younger and older women, respectively.

"Despite not having received adjuvant chemotherapy, the older series had clinical outcome similar to the younger patients, almost half of which had chemotherapy," Dr. Cheung and team reported at the time.

The current investigation, therefore, looked to see whether age was an important factor in determining clinical outcome, and if so, whether there were any biologic markers.

Older women were found to be more likely to have larger tumors than do younger women, with 66.7% and 50.4% (P = .002), respectively, having tumors of 2 cm or greater in size. There was no difference between them in axillary stage or nodal status.

Fewer women aged 70 years and above had grade 3 tumors: 79.8%, vs. 90.9% of the younger women (P = .007).

Biomarker analysis showed 48% vs. 87.7% (P less than .001) of tumor samples were Ki67- and 44.6% vs. 55.6% (P = .02) p53-positive, comparing the older and younger women. There was also decreased expression of E-cadherin (P = .002) and CK 7/8 (P = .005), but increased expression of bcl2 (P less than .001), CK14 (P = .03), and CK18 (P less than .001) in the older women.

The findings are counterintuitive to what might be expected commented Dr. Catherine Terret of Centre Léon Bérard, in Lyon, France.

"I think this is surprising for the clinician because my feeling is triple-negative breast cancer in the elderly is a very aggressive tumor," Dr. Terret, who was not involved in the study, said. "I’m really surprised [the] biologic results don’t go in the same way as my clinical opinion."

Dr. Cheung and Dr. Terret had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women with primary, operable, triple-negative breast cancer may have less aggressive tumor biology despite being treated for larger tumors than their younger counterparts, new data suggest.

Tumor samples taken from women aged 70 years or older were found to be of lower grade with significantly lower expression of the tumor markers Ki67 and p53 than seen in younger women, investigators reported at the annual meeting of the International Society of Geriatric Oncology (SIOG).

These data may help explain why similar clinical outcomes were achieved despite aggressive adjuvant chemotherapy not being given to the more elderly women, said investigator Dr. Kwok-Leung Cheung, of the University of Nottingham, England. "The precise place of adjuvant chemotherapy in the treatment of these patients has yet to be defined," he said.

The new report adds to previous findings presented at the American Society of Clinical Oncology (ASCO) meeting in 2011, (J. Clin. Oncol. 2011;29:abstr 1057), Dr. Cheung noted.

At ASCO, Dr. Cheung and his coauthors reported that they had identified 127 older women with triple-negative breast cancer among more than 2,000 women, aged 70 years and older, who had been treated over a 36-year period (1973-2009) for early operable primary breast cancer at a single clinic and also who had good quality tumor samples available for tissue microarray analysis using indirect immunohistochemistry.

The initial study compared this group’s results with those of 342 women with triple-negative breast cancer in a previously characterized consecutive series of 1,809 patients treated at the same clinic from 1986 to 1998. The rates of 5-year breast cancer-specific survival (73% vs. 79%) and of local (10% vs. 14%), regional (11% vs. 14%), and distant (30% vs. 27%) recurrences were found to be similar in younger and older women, respectively.

"Despite not having received adjuvant chemotherapy, the older series had clinical outcome similar to the younger patients, almost half of which had chemotherapy," Dr. Cheung and team reported at the time.

The current investigation, therefore, looked to see whether age was an important factor in determining clinical outcome, and if so, whether there were any biologic markers.

Older women were found to be more likely to have larger tumors than do younger women, with 66.7% and 50.4% (P = .002), respectively, having tumors of 2 cm or greater in size. There was no difference between them in axillary stage or nodal status.

Fewer women aged 70 years and above had grade 3 tumors: 79.8%, vs. 90.9% of the younger women (P = .007).

Biomarker analysis showed 48% vs. 87.7% (P less than .001) of tumor samples were Ki67- and 44.6% vs. 55.6% (P = .02) p53-positive, comparing the older and younger women. There was also decreased expression of E-cadherin (P = .002) and CK 7/8 (P = .005), but increased expression of bcl2 (P less than .001), CK14 (P = .03), and CK18 (P less than .001) in the older women.

The findings are counterintuitive to what might be expected commented Dr. Catherine Terret of Centre Léon Bérard, in Lyon, France.

"I think this is surprising for the clinician because my feeling is triple-negative breast cancer in the elderly is a very aggressive tumor," Dr. Terret, who was not involved in the study, said. "I’m really surprised [the] biologic results don’t go in the same way as my clinical opinion."

Dr. Cheung and Dr. Terret had no relevant financial disclosures.

MANCHESTER, ENGLAND – Older women with primary, operable, triple-negative breast cancer may have less aggressive tumor biology despite being treated for larger tumors than their younger counterparts, new data suggest.

Tumor samples taken from women aged 70 years or older were found to be of lower grade with significantly lower expression of the tumor markers Ki67 and p53 than seen in younger women, investigators reported at the annual meeting of the International Society of Geriatric Oncology (SIOG).

These data may help explain why similar clinical outcomes were achieved despite aggressive adjuvant chemotherapy not being given to the more elderly women, said investigator Dr. Kwok-Leung Cheung, of the University of Nottingham, England. "The precise place of adjuvant chemotherapy in the treatment of these patients has yet to be defined," he said.

The new report adds to previous findings presented at the American Society of Clinical Oncology (ASCO) meeting in 2011, (J. Clin. Oncol. 2011;29:abstr 1057), Dr. Cheung noted.

At ASCO, Dr. Cheung and his coauthors reported that they had identified 127 older women with triple-negative breast cancer among more than 2,000 women, aged 70 years and older, who had been treated over a 36-year period (1973-2009) for early operable primary breast cancer at a single clinic and also who had good quality tumor samples available for tissue microarray analysis using indirect immunohistochemistry.

The initial study compared this group’s results with those of 342 women with triple-negative breast cancer in a previously characterized consecutive series of 1,809 patients treated at the same clinic from 1986 to 1998. The rates of 5-year breast cancer-specific survival (73% vs. 79%) and of local (10% vs. 14%), regional (11% vs. 14%), and distant (30% vs. 27%) recurrences were found to be similar in younger and older women, respectively.

"Despite not having received adjuvant chemotherapy, the older series had clinical outcome similar to the younger patients, almost half of which had chemotherapy," Dr. Cheung and team reported at the time.

The current investigation, therefore, looked to see whether age was an important factor in determining clinical outcome, and if so, whether there were any biologic markers.

Older women were found to be more likely to have larger tumors than do younger women, with 66.7% and 50.4% (P = .002), respectively, having tumors of 2 cm or greater in size. There was no difference between them in axillary stage or nodal status.

Fewer women aged 70 years and above had grade 3 tumors: 79.8%, vs. 90.9% of the younger women (P = .007).

Biomarker analysis showed 48% vs. 87.7% (P less than .001) of tumor samples were Ki67- and 44.6% vs. 55.6% (P = .02) p53-positive, comparing the older and younger women. There was also decreased expression of E-cadherin (P = .002) and CK 7/8 (P = .005), but increased expression of bcl2 (P less than .001), CK14 (P = .03), and CK18 (P less than .001) in the older women.

The findings are counterintuitive to what might be expected commented Dr. Catherine Terret of Centre Léon Bérard, in Lyon, France.

"I think this is surprising for the clinician because my feeling is triple-negative breast cancer in the elderly is a very aggressive tumor," Dr. Terret, who was not involved in the study, said. "I’m really surprised [the] biologic results don’t go in the same way as my clinical opinion."

Dr. Cheung and Dr. Terret had no relevant financial disclosures.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, con-trolled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment vs. those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately, there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor (EGFR) inhibitor in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were rand-omized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud D. Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well-designed and -conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline, and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an adviser for Merck.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, con-trolled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment vs. those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately, there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor (EGFR) inhibitor in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were rand-omized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud D. Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well-designed and -conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline, and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an adviser for Merck.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, con-trolled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment vs. those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately, there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor (EGFR) inhibitor in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were rand-omized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud D. Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well-designed and -conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline, and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an adviser for Merck.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, controlled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment versus those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR, = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor inhibitor (EGFR) in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were randomized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well designed and conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an advisor for Merck.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, controlled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment versus those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR, = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor inhibitor (EGFR) in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were randomized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well designed and conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an advisor for Merck.

VIENNA – Adding cetuximab to first-line chemotherapy for gastric cancer was associated with a worse benefit-to-risk ratio in the open-label, randomized, controlled, phase III EXPAND trial.

Investigators reported that progression-free survival was nonsignificantly decreased in patients who had received cetuximab (Erbitux) in addition to capecitabine (Xeloda) and cisplatin treatment versus those just receiving the chemotherapy doublet. Progression-free survival, which was the primary end point, was 4.4 months versus 5.6 months, respectively, with a hazard ratio (HR) of 1.09 (P = .3158).

There was also no benefit in overall survival or objective response rates. Overall survival was 9.4 months vs. 10.7 months (HR, = 1.0; P = .96). The best objective response rates were 30% and 29%, respectively.

"Unfortunately there was no benefit from adding cetuximab to chemotherapy [consisting of] capecitabine and cisplatin as first-line treatment for advanced gastric cancer," said Dr. Florian Lordick, who presented the findings at the European Society for Medical Oncology Congress.

"The results are consistent across subgroups," added Dr. Lordick, of the University Cancer Center Leipzig in Germany.

This is not the first disappointment seen with the use of an epidermal growth factor receptor inhibitor (EGFR) in gastric cancer. Recently reported results of the REAL-3 trial showed that panitumumab (Vectibix) was also not of benefit when added to standard chemotherapy for esophagogastric cancer.

Cetuximab also failed to show a benefit in patients when added to adjuvant oxaliplatin-containing chemotherapy for advanced metastatic colorectal cancer in the PETACC8 trial.

It is approved by the Food and Drug Administration in combination with irinotecan-containing regimens against EGFR-expressing metastatic colorectal cancer.

In the EXPAND study, 870 patients with unresected, advanced adenocarcinoma of the stomach gastric or gastroesophageal junction were randomized to receive cisplatin (80 mg/m² on day 1) and capecitabine (1,000 mg/m² twice daily, starting the evening of day 1 until the morning of day 15) with or without additional cetuximab (400 mg/m² initial dose, then 250 mg/m² per week).

The median age of enrolled patients was 59-60 years. Three quarters of participants were men and the main tumor site was the stomach in about a third of the cases with almost all patients having metastatic disease.

"Interestingly, the rate of hematologic adverse events was somewhat lower in the chemotherapy plus cetuximab arm," Dr. Lordick said. Compared with chemotherapy only, the rates of grade 3/4 neutropenia were 22% with cetuximab and 32% without. Grades 3/4 anemia occurred in 9% vs. 11% of patients, respectively.

"This is in contrast to other studies that have been performed in colorectal cancer, head and neck cancer, and lung cancer, where usually an increase of hematologic toxicity is seen with the administration of cetuximab in combination with chemotherapy," Dr. Lordick observed.

Nonhematologic adverse events, however, were more common in the cetuximab-containing vs. cetuximab-free arm, including grade 3 or 4 skin reactions (13% vs. 0%), diarrhea (8% vs. 4%), hand-foot syndrome (7% vs. 2%), hypomagnesemia (11% vs. 1%), and hypokalemia (13% vs. 9%).

Patients given the cetuximab-containing regimen also had a slightly higher rate of grade 3/4 cardiac adverse events (6.7% vs. 4.1 %).

"This study confirms a little bit what we heard at ASCO in the REAL-3 trial," said Dr. Arnaud Roth of Geneva University Hospital. Dr. Roth, who was not involved in the EXPAND study, noted that it was a well designed and conducted study and although negative, provided an excellent opportunity to conduct translational research.

However, Dr. Roth disagreed that this was the right setting to learn much more about anti-EGFRs and gastric cancer. Nevertheless, gaining access to the data and biospecimens was important and "a moral obligation" considering the patients who had given their consent for their participation in the trial.

"The good news is that tissue is available from 97% of patients and biomarker analysis is ongoing," Dr. Lordick said prior to Dr. Roth’s comments.

The study was funded by Merck KGaA. Dr. Lordick has received research funding and honoraria from Merck KGaA, GlaxoSmithKline and Fresenius Biotech, and advisory fees from Amgen, Ganymed GmbH, Ribological GmbH, and Roche. Dr. Roth has acted as an advisor for Merck.