Patrice Wendling

CHICAGO– Five-year survival rates are nearly identical for small lung carcinomas classified as adenocarcinoma in situ or minimally invasive adenocarcinoma, a systematic review shows.

At 5 years, disease-free survival was 97% for patients with lung adenocarcinoma in situ (AIS) and 96.7% in those with minimally invasive adenocarcinoma (MIA) (P = .34).

Overall survival rates were 97.5% and 96% (P = .58).

“Our findings raise questions regarding the necessity of classifying these types of tumors into two separate categories when it may not provide any additional prognostic information,” lead author Madhusmita Behera, Ph.D., said during a briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

The review included 18 clinical studies involving 863 patients with tumors 3 cm or less in size that were classified as AIS (no tumor invasion) or MIA (≤ 0.5 cm foci of invasion), according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international lung adenocarcinoma classification (J. Thor. Oncol. 2011;6:244-85).

Part of the rationale for separating AIS and MIS was that it was believed patients with minimal invasion would have worse prognosis, Dr. Behera, a researcher at the Winship Cancer Institute of Emory University, Atlanta, explained.

Instead, “Patients who have minimal invasion have equally great survival outcomes as those with adenocarcinoma in situ,” she said. “That’s the message we wanted to give out, that patients have excellent outcomes regardless of what category they belong to.”

The studies were published between 2011 and 2014 and included 451 AIS patients and 344 MIA patients. One study reported survival data on 68 patients with AIS and MIA grouped together.

All patients underwent surgical resection. There was no evidence that patients with MIA tumors received more treatment, Dr. Behera said.

Press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado, Denver, said oncologists usually think of invasive cancers as being more serious than adenocarcinoma in situ and possibly needing more intensive treatment. The outcomes in both groups, however, were excellent and treatment, usually surgical resection, should be the same in both groups.

Dr. Gaspar went on to say that too often the public and physicians think of lung cancer as a male gender cancer occurring in current or former smokers, but that Dr. Behera’s study reminds us that lung cancer is increasingly common in nonsmokers and women.

Of the 863 patients, 61% were female and 43% were smokers. The median age was 67.5 years and median tumor size 1.3 cm.

For the whole population, the 5-year disease-free survival rate was 97.7% and overall survival rate 97.3%.

pwendling@frontlinemedcom.com

CHICAGO– Five-year survival rates are nearly identical for small lung carcinomas classified as adenocarcinoma in situ or minimally invasive adenocarcinoma, a systematic review shows.

At 5 years, disease-free survival was 97% for patients with lung adenocarcinoma in situ (AIS) and 96.7% in those with minimally invasive adenocarcinoma (MIA) (P = .34).

Overall survival rates were 97.5% and 96% (P = .58).

“Our findings raise questions regarding the necessity of classifying these types of tumors into two separate categories when it may not provide any additional prognostic information,” lead author Madhusmita Behera, Ph.D., said during a briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

The review included 18 clinical studies involving 863 patients with tumors 3 cm or less in size that were classified as AIS (no tumor invasion) or MIA (≤ 0.5 cm foci of invasion), according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international lung adenocarcinoma classification (J. Thor. Oncol. 2011;6:244-85).

Part of the rationale for separating AIS and MIS was that it was believed patients with minimal invasion would have worse prognosis, Dr. Behera, a researcher at the Winship Cancer Institute of Emory University, Atlanta, explained.

Instead, “Patients who have minimal invasion have equally great survival outcomes as those with adenocarcinoma in situ,” she said. “That’s the message we wanted to give out, that patients have excellent outcomes regardless of what category they belong to.”

The studies were published between 2011 and 2014 and included 451 AIS patients and 344 MIA patients. One study reported survival data on 68 patients with AIS and MIA grouped together.

All patients underwent surgical resection. There was no evidence that patients with MIA tumors received more treatment, Dr. Behera said.

Press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado, Denver, said oncologists usually think of invasive cancers as being more serious than adenocarcinoma in situ and possibly needing more intensive treatment. The outcomes in both groups, however, were excellent and treatment, usually surgical resection, should be the same in both groups.

Dr. Gaspar went on to say that too often the public and physicians think of lung cancer as a male gender cancer occurring in current or former smokers, but that Dr. Behera’s study reminds us that lung cancer is increasingly common in nonsmokers and women.

Of the 863 patients, 61% were female and 43% were smokers. The median age was 67.5 years and median tumor size 1.3 cm.

For the whole population, the 5-year disease-free survival rate was 97.7% and overall survival rate 97.3%.

pwendling@frontlinemedcom.com

CHICAGO– Five-year survival rates are nearly identical for small lung carcinomas classified as adenocarcinoma in situ or minimally invasive adenocarcinoma, a systematic review shows.

At 5 years, disease-free survival was 97% for patients with lung adenocarcinoma in situ (AIS) and 96.7% in those with minimally invasive adenocarcinoma (MIA) (P = .34).

Overall survival rates were 97.5% and 96% (P = .58).

“Our findings raise questions regarding the necessity of classifying these types of tumors into two separate categories when it may not provide any additional prognostic information,” lead author Madhusmita Behera, Ph.D., said during a briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

The review included 18 clinical studies involving 863 patients with tumors 3 cm or less in size that were classified as AIS (no tumor invasion) or MIA (≤ 0.5 cm foci of invasion), according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international lung adenocarcinoma classification (J. Thor. Oncol. 2011;6:244-85).

Part of the rationale for separating AIS and MIS was that it was believed patients with minimal invasion would have worse prognosis, Dr. Behera, a researcher at the Winship Cancer Institute of Emory University, Atlanta, explained.

Instead, “Patients who have minimal invasion have equally great survival outcomes as those with adenocarcinoma in situ,” she said. “That’s the message we wanted to give out, that patients have excellent outcomes regardless of what category they belong to.”

The studies were published between 2011 and 2014 and included 451 AIS patients and 344 MIA patients. One study reported survival data on 68 patients with AIS and MIA grouped together.

All patients underwent surgical resection. There was no evidence that patients with MIA tumors received more treatment, Dr. Behera said.

Press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado, Denver, said oncologists usually think of invasive cancers as being more serious than adenocarcinoma in situ and possibly needing more intensive treatment. The outcomes in both groups, however, were excellent and treatment, usually surgical resection, should be the same in both groups.

Dr. Gaspar went on to say that too often the public and physicians think of lung cancer as a male gender cancer occurring in current or former smokers, but that Dr. Behera’s study reminds us that lung cancer is increasingly common in nonsmokers and women.

Of the 863 patients, 61% were female and 43% were smokers. The median age was 67.5 years and median tumor size 1.3 cm.

For the whole population, the 5-year disease-free survival rate was 97.7% and overall survival rate 97.3%.

pwendling@frontlinemedcom.com

PHILADELPHIA – A single injection of the investigational 4-antigen SA4Ag vaccine was well tolerated and induced robust antibody responses against Staphylococcusaureus in healthy adults in a phase I/II study.

“The very quick development of antibodies suggest that the vaccine could be used pre-operatively [2-3 weeks] for elective surgeries that are at higher risk of Staph. infection, such as thoracotomy or insertion of rods for scoliosis or spinal fusion,” Dr. Robert W. Frenck Jr. said in an interview at Infectious Diseases Week 2014.

As to the durability of responses, antibody levels for all four antigens in the vaccine rose rapidly and then decayed slowly over the next 12 months, he said. “The results support the continued development of SA4Ag for the prevention of invasive S. aureus disease in at-risk adults, including those undergoing elective surgery.”

There is no licensed vaccine that prevents invasive S. aureus infection, although several multi-antigen vaccines are in development.

SA4Ag vaccine is a second-generation vaccine to Pfizer’s 3-antigen SA3AG candidate vaccine and was granted Fast Track designation by the U.S. Food and Drug Administration in February 2014, according to the manufacturer.

SA4Ag contains capsular polysaccharides serotypes 5 and 8 (CP5 and CP8) individually conjugated to CRM₁₉₇, a recombinant surface protein clumping factor A (rmClfA), with a recombinant manganese transporter protein C known as rP305A. Each component was selected based on the virulence of these antigens in S. aureus infections, Dr. Frenck Jr., professor of pediatrics and interim director of infectious diseases, at Cincinnati (Ohio) Children’s Hospital Medical Center, said.

The study stratified 456 healthy adults by age (18-49 years and 50-64 years) and then randomly assigned them to receive a single injection of placebo or one of three formulations of SA4Ag: fixed doses of 30 μg CP5-CRM₁₉₇, 30 μg CP8-CRM₁₉₇, and 60 μg rmClfA, and either a low- (20 μg), mid- (60 μg), or high- (200 μg) rP305A dose.

The participants average age was 45 years, 57% were female, 73% were white, and 87.5% completed the study through month 12.

Local reactions reported through day 14 were mild or moderate, and systemic events and other adverse events were comparable across all groups, Dr. Frenck Jr. said. No vaccine-related serious adverse events or deaths were reported.

At day 29, all participants vaccinated with SA4Ag achieved the CP5 opsonophagocytic activity (OPA) threshold (≥ 1,000 titers) and 96%–99% met the CP8 OPA threshold (≥ 2,000 titers).

“The percentage of subjects reaching the threshold is equivalent for each one of the vaccine doses, indicating that the rP305A did not affect the immune response to the other components in the vaccine,” Dr. Frenck Jr. said.

Less than 25% of patients given placebo achieved the CP5 or CP8 OPA thresholds.

Immune responses to ClfA were robust by day 15 and did not vary by the dose of rP305A, again suggesting that rP305A does not affect the other three antigens in the vaccine, he observed.

Immune responses to the rP305A antigen were dose dependent, with the percentage of patients with a threshold response increasing step-wise from the low (47%), mid (63.2%), and high (83%) doses.

By day 29, there was a very brisk rise in geometric mean titers for CP5. Responses did not differ by rP305A dose or across age groups, with a similar pattern observed for CP8 and ClfA, Dr. Fenck Jr. said.

Session co-moderator Dr. Walter Orenstein, from Emory University in Atlanta, commented that the rate of decay post-vaccination was promising, particularly compared with that observed with meningococcal vaccines.

The vaccine “program is exciting because it not only relies on just antibody, but it actually looks at functional responses and those functional responses have some correlate with protection against staphylococcal disease,” he said in an interview. High-risk populations, like renal dialysis patients, were not studied and it would be interesting to see how well they would respond. “Previous studies have shown transient benefits for those types of populations.”

pwendling@frontlinemedcom.com

PHILADELPHIA – A single injection of the investigational 4-antigen SA4Ag vaccine was well tolerated and induced robust antibody responses against Staphylococcusaureus in healthy adults in a phase I/II study.

“The very quick development of antibodies suggest that the vaccine could be used pre-operatively [2-3 weeks] for elective surgeries that are at higher risk of Staph. infection, such as thoracotomy or insertion of rods for scoliosis or spinal fusion,” Dr. Robert W. Frenck Jr. said in an interview at Infectious Diseases Week 2014.

As to the durability of responses, antibody levels for all four antigens in the vaccine rose rapidly and then decayed slowly over the next 12 months, he said. “The results support the continued development of SA4Ag for the prevention of invasive S. aureus disease in at-risk adults, including those undergoing elective surgery.”

There is no licensed vaccine that prevents invasive S. aureus infection, although several multi-antigen vaccines are in development.

SA4Ag vaccine is a second-generation vaccine to Pfizer’s 3-antigen SA3AG candidate vaccine and was granted Fast Track designation by the U.S. Food and Drug Administration in February 2014, according to the manufacturer.

SA4Ag contains capsular polysaccharides serotypes 5 and 8 (CP5 and CP8) individually conjugated to CRM₁₉₇, a recombinant surface protein clumping factor A (rmClfA), with a recombinant manganese transporter protein C known as rP305A. Each component was selected based on the virulence of these antigens in S. aureus infections, Dr. Frenck Jr., professor of pediatrics and interim director of infectious diseases, at Cincinnati (Ohio) Children’s Hospital Medical Center, said.

The study stratified 456 healthy adults by age (18-49 years and 50-64 years) and then randomly assigned them to receive a single injection of placebo or one of three formulations of SA4Ag: fixed doses of 30 μg CP5-CRM₁₉₇, 30 μg CP8-CRM₁₉₇, and 60 μg rmClfA, and either a low- (20 μg), mid- (60 μg), or high- (200 μg) rP305A dose.

The participants average age was 45 years, 57% were female, 73% were white, and 87.5% completed the study through month 12.

Local reactions reported through day 14 were mild or moderate, and systemic events and other adverse events were comparable across all groups, Dr. Frenck Jr. said. No vaccine-related serious adverse events or deaths were reported.

At day 29, all participants vaccinated with SA4Ag achieved the CP5 opsonophagocytic activity (OPA) threshold (≥ 1,000 titers) and 96%–99% met the CP8 OPA threshold (≥ 2,000 titers).

“The percentage of subjects reaching the threshold is equivalent for each one of the vaccine doses, indicating that the rP305A did not affect the immune response to the other components in the vaccine,” Dr. Frenck Jr. said.

Less than 25% of patients given placebo achieved the CP5 or CP8 OPA thresholds.

Immune responses to ClfA were robust by day 15 and did not vary by the dose of rP305A, again suggesting that rP305A does not affect the other three antigens in the vaccine, he observed.

Immune responses to the rP305A antigen were dose dependent, with the percentage of patients with a threshold response increasing step-wise from the low (47%), mid (63.2%), and high (83%) doses.

By day 29, there was a very brisk rise in geometric mean titers for CP5. Responses did not differ by rP305A dose or across age groups, with a similar pattern observed for CP8 and ClfA, Dr. Fenck Jr. said.

Session co-moderator Dr. Walter Orenstein, from Emory University in Atlanta, commented that the rate of decay post-vaccination was promising, particularly compared with that observed with meningococcal vaccines.

The vaccine “program is exciting because it not only relies on just antibody, but it actually looks at functional responses and those functional responses have some correlate with protection against staphylococcal disease,” he said in an interview. High-risk populations, like renal dialysis patients, were not studied and it would be interesting to see how well they would respond. “Previous studies have shown transient benefits for those types of populations.”

pwendling@frontlinemedcom.com

PHILADELPHIA – A single injection of the investigational 4-antigen SA4Ag vaccine was well tolerated and induced robust antibody responses against Staphylococcusaureus in healthy adults in a phase I/II study.

“The very quick development of antibodies suggest that the vaccine could be used pre-operatively [2-3 weeks] for elective surgeries that are at higher risk of Staph. infection, such as thoracotomy or insertion of rods for scoliosis or spinal fusion,” Dr. Robert W. Frenck Jr. said in an interview at Infectious Diseases Week 2014.

As to the durability of responses, antibody levels for all four antigens in the vaccine rose rapidly and then decayed slowly over the next 12 months, he said. “The results support the continued development of SA4Ag for the prevention of invasive S. aureus disease in at-risk adults, including those undergoing elective surgery.”

There is no licensed vaccine that prevents invasive S. aureus infection, although several multi-antigen vaccines are in development.

SA4Ag vaccine is a second-generation vaccine to Pfizer’s 3-antigen SA3AG candidate vaccine and was granted Fast Track designation by the U.S. Food and Drug Administration in February 2014, according to the manufacturer.

SA4Ag contains capsular polysaccharides serotypes 5 and 8 (CP5 and CP8) individually conjugated to CRM₁₉₇, a recombinant surface protein clumping factor A (rmClfA), with a recombinant manganese transporter protein C known as rP305A. Each component was selected based on the virulence of these antigens in S. aureus infections, Dr. Frenck Jr., professor of pediatrics and interim director of infectious diseases, at Cincinnati (Ohio) Children’s Hospital Medical Center, said.

The study stratified 456 healthy adults by age (18-49 years and 50-64 years) and then randomly assigned them to receive a single injection of placebo or one of three formulations of SA4Ag: fixed doses of 30 μg CP5-CRM₁₉₇, 30 μg CP8-CRM₁₉₇, and 60 μg rmClfA, and either a low- (20 μg), mid- (60 μg), or high- (200 μg) rP305A dose.

The participants average age was 45 years, 57% were female, 73% were white, and 87.5% completed the study through month 12.

Local reactions reported through day 14 were mild or moderate, and systemic events and other adverse events were comparable across all groups, Dr. Frenck Jr. said. No vaccine-related serious adverse events or deaths were reported.

At day 29, all participants vaccinated with SA4Ag achieved the CP5 opsonophagocytic activity (OPA) threshold (≥ 1,000 titers) and 96%–99% met the CP8 OPA threshold (≥ 2,000 titers).

“The percentage of subjects reaching the threshold is equivalent for each one of the vaccine doses, indicating that the rP305A did not affect the immune response to the other components in the vaccine,” Dr. Frenck Jr. said.

Less than 25% of patients given placebo achieved the CP5 or CP8 OPA thresholds.

Immune responses to ClfA were robust by day 15 and did not vary by the dose of rP305A, again suggesting that rP305A does not affect the other three antigens in the vaccine, he observed.

Immune responses to the rP305A antigen were dose dependent, with the percentage of patients with a threshold response increasing step-wise from the low (47%), mid (63.2%), and high (83%) doses.

By day 29, there was a very brisk rise in geometric mean titers for CP5. Responses did not differ by rP305A dose or across age groups, with a similar pattern observed for CP8 and ClfA, Dr. Fenck Jr. said.

Session co-moderator Dr. Walter Orenstein, from Emory University in Atlanta, commented that the rate of decay post-vaccination was promising, particularly compared with that observed with meningococcal vaccines.

The vaccine “program is exciting because it not only relies on just antibody, but it actually looks at functional responses and those functional responses have some correlate with protection against staphylococcal disease,” he said in an interview. High-risk populations, like renal dialysis patients, were not studied and it would be interesting to see how well they would respond. “Previous studies have shown transient benefits for those types of populations.”

pwendling@frontlinemedcom.com

PHILADELPHIA– The swath cut by the Ebola virus in West Africa needs to be understood by Westerners in the context of the health care infrastructure available in West Africa, according to Dr. Robert Fowler, who worked as a consulting physician with the World Health Organization and health ministries in West Africa.

The health care infrastructure in West Africa is inadequate to support implementation of infection prevention and control and triage, including even the most basic standard precautions, such as access to soap and water, alcohol-based hand rubs, and sharps disposal boxes, safe needle handling, and rational use of personal protective equipment.

During a special session on the Ebola virus at the recent Infectious Diseases Week 2014, Dr. Fowler described infected patients lying outdoors because of a lack of beds, soiled personal protective equipment piled up where dogs and chickens could run through them, and a room where an Ebola patient hemorrhaged to death after being left untended for days.

Couple this with a limited ability to monitor patients or provide lifesaving rehydration therapy, and one begins to see how health systems in the United States, Canada, and Western Europe are far better prepared to handle the crisis than were their West African counterparts, according to Dr. Fowler of the department of critical care medicine, University of Toronto.

In a video interview, Dr. Fowler discussed the fears surrounding Ebola in the United States and Canada, and highlighted the realities of those countries’ capabilities to combat the outbreak.

Dr. Fowler reported no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA– The swath cut by the Ebola virus in West Africa needs to be understood by Westerners in the context of the health care infrastructure available in West Africa, according to Dr. Robert Fowler, who worked as a consulting physician with the World Health Organization and health ministries in West Africa.

The health care infrastructure in West Africa is inadequate to support implementation of infection prevention and control and triage, including even the most basic standard precautions, such as access to soap and water, alcohol-based hand rubs, and sharps disposal boxes, safe needle handling, and rational use of personal protective equipment.

During a special session on the Ebola virus at the recent Infectious Diseases Week 2014, Dr. Fowler described infected patients lying outdoors because of a lack of beds, soiled personal protective equipment piled up where dogs and chickens could run through them, and a room where an Ebola patient hemorrhaged to death after being left untended for days.

Couple this with a limited ability to monitor patients or provide lifesaving rehydration therapy, and one begins to see how health systems in the United States, Canada, and Western Europe are far better prepared to handle the crisis than were their West African counterparts, according to Dr. Fowler of the department of critical care medicine, University of Toronto.

In a video interview, Dr. Fowler discussed the fears surrounding Ebola in the United States and Canada, and highlighted the realities of those countries’ capabilities to combat the outbreak.

Dr. Fowler reported no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA– The swath cut by the Ebola virus in West Africa needs to be understood by Westerners in the context of the health care infrastructure available in West Africa, according to Dr. Robert Fowler, who worked as a consulting physician with the World Health Organization and health ministries in West Africa.

The health care infrastructure in West Africa is inadequate to support implementation of infection prevention and control and triage, including even the most basic standard precautions, such as access to soap and water, alcohol-based hand rubs, and sharps disposal boxes, safe needle handling, and rational use of personal protective equipment.

During a special session on the Ebola virus at the recent Infectious Diseases Week 2014, Dr. Fowler described infected patients lying outdoors because of a lack of beds, soiled personal protective equipment piled up where dogs and chickens could run through them, and a room where an Ebola patient hemorrhaged to death after being left untended for days.

Couple this with a limited ability to monitor patients or provide lifesaving rehydration therapy, and one begins to see how health systems in the United States, Canada, and Western Europe are far better prepared to handle the crisis than were their West African counterparts, according to Dr. Fowler of the department of critical care medicine, University of Toronto.

In a video interview, Dr. Fowler discussed the fears surrounding Ebola in the United States and Canada, and highlighted the realities of those countries’ capabilities to combat the outbreak.

Dr. Fowler reported no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Patrice Wendling/Frontline Medical News

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Patrice Wendling/Frontline Medical News

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA – Community associated Clostridium difficile infections continue to increase, rising most rapidly in children, a new study shows.

Age-related changes in C. difficile infection (CDI) also are being paralleled by age-dependent changes in the use of antibiotics, proton pump inhibitors (PPIs), and histamine type 2 receptor (H2) blockers, study author Dr. Howard Faden reported at an annual scientific meeting on infectious diseases.

Patrice Wendling/Frontline Medical News

Children aged 1-18 years had the highest use of antibiotics at 35.39%. This was followed closely by those younger than 1 year of age at 34.01%, who also had the highest use of H2 blockers at 4.30%.

“While children less than 1 year old may or may not develop community-associated C. difficile, their high rate of use of antibiotics and H2 blockers may be associated with higher rates of CD colonization. This could result in the spread of CD in the community,” said Dr. Faden, professor and chief of infectious diseases at the State University of New York at Buffalo.

Dr. Faden and his colleagues used New York State Medicaid data for an annual population of approximately 5 million recipients to calculate outpatient CDI and medication use from 2005 through 2012. Because CD is not considered a pathogen in the first year of life, infants younger than 1 year were included in drug use calculations, but not considered in the overall CDI analysis.

Over the study period, the overall annual incidence of community-acquired CDI increased significantly from 0.13% to 0.32% (P < .01), Dr. Faden said.

The highest incidence was among adults 65 years and older, increasing from 0.28% in 2005 to a peak of 0.54% in 2011, before declining slightly to 0.51% in 2012.

The incidence also increased in adults aged 19-64 years (0.10% -0.29%), but there was a “tremendous rise” in the diagnosis of community acquired CDI in children aged 1-18 years (0.01%-0.05%), Dr. Faden said.

“Granted, it’s much less than the adults, but the rise is much greater,” he remarked.

The differences between years were statistically significant for all age groups (P < .01).

For the total population, the annual use of antibiotics was 25%-35%, surpassing the use of prescribed PPIs at 7% and H2 blockers at 2.5%. “What’s startling to me is that roughly one in three patients in New York have had an antibiotic prescription in the preceding year,” Dr. Faden said in an interview. “When you consider that PPIs and H2 blockers are readily sold over the counter and our analysis accounts for only those that are prescribed, these are clearly underestimates.”

Notably, the use of two or three drug classes was significantly more common in CDI-positive than CDI-negative patients, regardless of age. The same relationship was not seen for one or no drug use.

Mayo Clinic in Minnesota also recently reported that the overall incidence of community-acquired CDI is increasing and that community-acquired CDI patients are significantly younger (median age 50 years) than those with hospital-acquired infections.

The study authors question, however, whether novel risk factors may be playing a role in acquisition, noting that 22% of all patients contracting CDI in the community had no prior antibiotic exposure, and 78% had no exposure to gastric acid suppression drugs (Am. J. Gastroenterol. 2012;107:89-95).

One of the novel risk factors may be having infants younger than 1 year in the household, Dr. Faden said in an interview. The frequent, but unsupported use of PPIs and H2 blockers in this age group further increases colonization, which can be easily transmitted through diaper changes. A study supports this theory, finding that patients with CDI and no or low-level outpatient health care exposure were significantly more likely to be exposed to infants younger than 1 year (JAMA Intern. Med. 2013;173:1359-67).

IDWeek 2014 is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Faden reported having no financial disclosures.

pwendling@frontlinemedcom.com

MADRID – The future of lung cancer vaccines was dealt a strong blow with a full look at the disappointing phase III MAGRIT results.

Lead author Dr. Johan Vansteenkiste described adjuvant vaccination as a promising strategy that was formally tested in the appropriate disease setting with an adequately designed and powered trial.

Patrice Wendling/Frontline Medical News

“This means for me, that therapeutic vaccination with the current technology does not work in lung cancer,” he concluded in a presidential symposium at the annual congress of the European Society for Medical Oncology.

The MAGRIT (MAGE-A3 as Adjuvant Non–Small Cell Lung Cancer Immunotherapy) study assessed the efficacy of MAGE-A3 cancer immunotherapy (MAGE-A3 CI) in completely resected stage IB to IIIA non–small cell lung cancer (NSCLC) positive for melanoma-associated antigen 3 (MAGE-A3).

MAGE-A3 is not expressed in normal cells but is found in about a third of stage IB-IIIA non–small cell lung cancer and in a variety of other cancers. The vaccine, which contains a recombinant MAGE-A3 protein and a novel immunostimulant AS15, previously showed activity in a small study of resected lung cancer.

In MAGRIT, however, adjuvant MAGE-A3 CI failed to best placebo on the coprimary end points of disease-free survival in the overall population (median 60.5 vs. 57.9 months; hazard ratio, 1.02; P = .73) and in those without adjuvant chemotherapy (median 58.0 vs. 56.9 months; HR, 0.97; P = .75).

There was no benefit observed in any subset analysis, Dr. Vansteenkiste, from University Hospitals Leuven, Belgium, said.

Vaccine developer GlaxoSmithKline announced this spring that MAGRIT was being stopped after failing to meet its first and second coprimary end points and acknowledging that the third coprimary end point of identifying patients with a potentially predictive gene signature wasn’t feasible.

Although MAGE-A3 CI is dead in the water for NSCLC, GSK said in a statement it plans to continue to search for a predictive gene signature for the vaccine in patients with melanoma in the phase III DERMA trial.

MAGRIT randomized 2,272 patients 2:1 to 13 intramuscular injections of recombinant MAGE-A3 CI or placebo over 27 months, with or without up to 4 cycles of platinum-based chemotherapy. Overall, 52% of patients received adjuvant chemotherapy and 98% had a performance status of 0 or 1. The median age was 63 years.

Median overall survival was not reached in either arm, although on a positive note, the modern approach used in the global trial will likely result in an expected 5-year overall survival above 50% in both arms, Dr. Vansteenkiste said enthusiastically. Overall, MAGE-A3 CI was generally well tolerated.

Invited discussant Dr. George Coukos, director of the Ludwig Center in Lausanne, Switzerland, said future opportunities for vaccines in NSCLC may lie in autologous whole tumor antigen vaccines and in personalized molecular vaccines based on mutanome analysis.

Dr. Martin Reck, chief oncology physician, with Hospital Grosshansdorf, Germany, said in a statement that the MAGRIT results are disappointing and that “The concept of vaccination in lung cancer has to be questioned and checkpoint inhibition might be pursued instead.”

pwendling@frontlinemedcom.com

MADRID – The future of lung cancer vaccines was dealt a strong blow with a full look at the disappointing phase III MAGRIT results.

Lead author Dr. Johan Vansteenkiste described adjuvant vaccination as a promising strategy that was formally tested in the appropriate disease setting with an adequately designed and powered trial.

Patrice Wendling/Frontline Medical News

“This means for me, that therapeutic vaccination with the current technology does not work in lung cancer,” he concluded in a presidential symposium at the annual congress of the European Society for Medical Oncology.

The MAGRIT (MAGE-A3 as Adjuvant Non–Small Cell Lung Cancer Immunotherapy) study assessed the efficacy of MAGE-A3 cancer immunotherapy (MAGE-A3 CI) in completely resected stage IB to IIIA non–small cell lung cancer (NSCLC) positive for melanoma-associated antigen 3 (MAGE-A3).

MAGE-A3 is not expressed in normal cells but is found in about a third of stage IB-IIIA non–small cell lung cancer and in a variety of other cancers. The vaccine, which contains a recombinant MAGE-A3 protein and a novel immunostimulant AS15, previously showed activity in a small study of resected lung cancer.

In MAGRIT, however, adjuvant MAGE-A3 CI failed to best placebo on the coprimary end points of disease-free survival in the overall population (median 60.5 vs. 57.9 months; hazard ratio, 1.02; P = .73) and in those without adjuvant chemotherapy (median 58.0 vs. 56.9 months; HR, 0.97; P = .75).

There was no benefit observed in any subset analysis, Dr. Vansteenkiste, from University Hospitals Leuven, Belgium, said.

Vaccine developer GlaxoSmithKline announced this spring that MAGRIT was being stopped after failing to meet its first and second coprimary end points and acknowledging that the third coprimary end point of identifying patients with a potentially predictive gene signature wasn’t feasible.

Although MAGE-A3 CI is dead in the water for NSCLC, GSK said in a statement it plans to continue to search for a predictive gene signature for the vaccine in patients with melanoma in the phase III DERMA trial.

MAGRIT randomized 2,272 patients 2:1 to 13 intramuscular injections of recombinant MAGE-A3 CI or placebo over 27 months, with or without up to 4 cycles of platinum-based chemotherapy. Overall, 52% of patients received adjuvant chemotherapy and 98% had a performance status of 0 or 1. The median age was 63 years.

Median overall survival was not reached in either arm, although on a positive note, the modern approach used in the global trial will likely result in an expected 5-year overall survival above 50% in both arms, Dr. Vansteenkiste said enthusiastically. Overall, MAGE-A3 CI was generally well tolerated.

Invited discussant Dr. George Coukos, director of the Ludwig Center in Lausanne, Switzerland, said future opportunities for vaccines in NSCLC may lie in autologous whole tumor antigen vaccines and in personalized molecular vaccines based on mutanome analysis.

Dr. Martin Reck, chief oncology physician, with Hospital Grosshansdorf, Germany, said in a statement that the MAGRIT results are disappointing and that “The concept of vaccination in lung cancer has to be questioned and checkpoint inhibition might be pursued instead.”

pwendling@frontlinemedcom.com

MADRID – The future of lung cancer vaccines was dealt a strong blow with a full look at the disappointing phase III MAGRIT results.

Lead author Dr. Johan Vansteenkiste described adjuvant vaccination as a promising strategy that was formally tested in the appropriate disease setting with an adequately designed and powered trial.

Patrice Wendling/Frontline Medical News

“This means for me, that therapeutic vaccination with the current technology does not work in lung cancer,” he concluded in a presidential symposium at the annual congress of the European Society for Medical Oncology.

The MAGRIT (MAGE-A3 as Adjuvant Non–Small Cell Lung Cancer Immunotherapy) study assessed the efficacy of MAGE-A3 cancer immunotherapy (MAGE-A3 CI) in completely resected stage IB to IIIA non–small cell lung cancer (NSCLC) positive for melanoma-associated antigen 3 (MAGE-A3).

MAGE-A3 is not expressed in normal cells but is found in about a third of stage IB-IIIA non–small cell lung cancer and in a variety of other cancers. The vaccine, which contains a recombinant MAGE-A3 protein and a novel immunostimulant AS15, previously showed activity in a small study of resected lung cancer.

In MAGRIT, however, adjuvant MAGE-A3 CI failed to best placebo on the coprimary end points of disease-free survival in the overall population (median 60.5 vs. 57.9 months; hazard ratio, 1.02; P = .73) and in those without adjuvant chemotherapy (median 58.0 vs. 56.9 months; HR, 0.97; P = .75).

There was no benefit observed in any subset analysis, Dr. Vansteenkiste, from University Hospitals Leuven, Belgium, said.

Vaccine developer GlaxoSmithKline announced this spring that MAGRIT was being stopped after failing to meet its first and second coprimary end points and acknowledging that the third coprimary end point of identifying patients with a potentially predictive gene signature wasn’t feasible.

Although MAGE-A3 CI is dead in the water for NSCLC, GSK said in a statement it plans to continue to search for a predictive gene signature for the vaccine in patients with melanoma in the phase III DERMA trial.

MAGRIT randomized 2,272 patients 2:1 to 13 intramuscular injections of recombinant MAGE-A3 CI or placebo over 27 months, with or without up to 4 cycles of platinum-based chemotherapy. Overall, 52% of patients received adjuvant chemotherapy and 98% had a performance status of 0 or 1. The median age was 63 years.

Median overall survival was not reached in either arm, although on a positive note, the modern approach used in the global trial will likely result in an expected 5-year overall survival above 50% in both arms, Dr. Vansteenkiste said enthusiastically. Overall, MAGE-A3 CI was generally well tolerated.

Invited discussant Dr. George Coukos, director of the Ludwig Center in Lausanne, Switzerland, said future opportunities for vaccines in NSCLC may lie in autologous whole tumor antigen vaccines and in personalized molecular vaccines based on mutanome analysis.

Dr. Martin Reck, chief oncology physician, with Hospital Grosshansdorf, Germany, said in a statement that the MAGRIT results are disappointing and that “The concept of vaccination in lung cancer has to be questioned and checkpoint inhibition might be pursued instead.”

pwendling@frontlinemedcom.com

MADRID – Evaluating one new oncology drug is hard enough, but a novel collaborative clinical trial is taking on the task of testing five experimental drugs at once.

The Lung-MAP trial is using genomic profiling to direct patients to one of five simultaneous sub-studies that best fits their tumor’s genomic profile.

The treatments are for second-line, recurrent squamous cell lung cancer, an area of tremendous unmet need, according to Dr. Roy Herbst, chair of the Lung-MAP steering committee and chief of medical oncology at the Yale Cancer Center, New Haven, Conn.

The novel design of the phase II/III trial should speed up assessment and approval of investigational drugs, and improve the likelihood that patients from the most highly academic to the most rural community sites will receive a targeted therapy.

“It’s really open throughout the country and that makes me very proud that we’re bringing molecular profiling and new drugs to patients of all resource levels,” Dr. Herbst said.

Watch our interview with Dr. Herbst at the annual congress of the European Society for Clinical Oncology, where he spoke about Lung-MAP in a special session on new clinical trial designs.

LungMAP is sponsored by the Southwest Oncology Group with collaboration from several public and private partners including the National Cancer Institute.

Groups interested in participating in Lung-MAP can contact Lung-MAP protocol coordinator Crystal Miwa at cmiwa@swog.org or Dr. Herbst at Roy.Herbst@yale.edu.

Details on the protocol are also available at clinicaltrials.gov or the Lung-MAP website.

Dr. Herbst reported serving on the science advisory board of Biothera, DiaTech Oncology, Koltan, and N of One.

pwendling@frontlinemedcom.com

MADRID – Evaluating one new oncology drug is hard enough, but a novel collaborative clinical trial is taking on the task of testing five experimental drugs at once.

The Lung-MAP trial is using genomic profiling to direct patients to one of five simultaneous sub-studies that best fits their tumor’s genomic profile.

The treatments are for second-line, recurrent squamous cell lung cancer, an area of tremendous unmet need, according to Dr. Roy Herbst, chair of the Lung-MAP steering committee and chief of medical oncology at the Yale Cancer Center, New Haven, Conn.

The novel design of the phase II/III trial should speed up assessment and approval of investigational drugs, and improve the likelihood that patients from the most highly academic to the most rural community sites will receive a targeted therapy.

“It’s really open throughout the country and that makes me very proud that we’re bringing molecular profiling and new drugs to patients of all resource levels,” Dr. Herbst said.

Watch our interview with Dr. Herbst at the annual congress of the European Society for Clinical Oncology, where he spoke about Lung-MAP in a special session on new clinical trial designs.

LungMAP is sponsored by the Southwest Oncology Group with collaboration from several public and private partners including the National Cancer Institute.

Groups interested in participating in Lung-MAP can contact Lung-MAP protocol coordinator Crystal Miwa at cmiwa@swog.org or Dr. Herbst at Roy.Herbst@yale.edu.

Details on the protocol are also available at clinicaltrials.gov or the Lung-MAP website.

Dr. Herbst reported serving on the science advisory board of Biothera, DiaTech Oncology, Koltan, and N of One.

pwendling@frontlinemedcom.com

MADRID – Evaluating one new oncology drug is hard enough, but a novel collaborative clinical trial is taking on the task of testing five experimental drugs at once.

The Lung-MAP trial is using genomic profiling to direct patients to one of five simultaneous sub-studies that best fits their tumor’s genomic profile.

The treatments are for second-line, recurrent squamous cell lung cancer, an area of tremendous unmet need, according to Dr. Roy Herbst, chair of the Lung-MAP steering committee and chief of medical oncology at the Yale Cancer Center, New Haven, Conn.

The novel design of the phase II/III trial should speed up assessment and approval of investigational drugs, and improve the likelihood that patients from the most highly academic to the most rural community sites will receive a targeted therapy.

“It’s really open throughout the country and that makes me very proud that we’re bringing molecular profiling and new drugs to patients of all resource levels,” Dr. Herbst said.

Watch our interview with Dr. Herbst at the annual congress of the European Society for Clinical Oncology, where he spoke about Lung-MAP in a special session on new clinical trial designs.

LungMAP is sponsored by the Southwest Oncology Group with collaboration from several public and private partners including the National Cancer Institute.

Groups interested in participating in Lung-MAP can contact Lung-MAP protocol coordinator Crystal Miwa at cmiwa@swog.org or Dr. Herbst at Roy.Herbst@yale.edu.

Details on the protocol are also available at clinicaltrials.gov or the Lung-MAP website.

Dr. Herbst reported serving on the science advisory board of Biothera, DiaTech Oncology, Koltan, and N of One.

pwendling@frontlinemedcom.com

MADRID – More complete blockade of the MAP kinase pathway with both a BRAF and MEK inhibitor decreased the risk of death by one-third among patients with advanced BRAF mutation–positive melanoma in the phase III COMBI-v study.

After a median follow-up of 10-11 months, the primary endpoint of overall survival was 17.2 months with the BRAF inhibitor vemurafenib (Zelboraf) alone, but had not been reached with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) (hazard ratio, 0.69; P = .005).

Patrice Wendling/Frontline Medical News

“This combination has met all the endpoints that were looked for, and I’d like to remind you that we compared this combination to an already very active drug,” study author Dr. Caroline Robert, head of dermatology at the Institut Gustave Roussy in Paris, said during a presidential session at the European Society for Medical Oncology Congress.

Patients in the combination arm had significantly better median progression-free survival than those given vemurafenib monotherapy (11.4 vs. 7.3 months; HR, 0.56; P < .001), as well as higher response rates (64% vs. 51%; P < .001), more complete responses (13% vs. 8%), and a longer duration of response (13.8 vs. 7.5 months).

COMBI-v was stopped early for efficacy at the interim analysis, which de facto became the final overall survival analysis presented by Dr. Robert.

The study evenly randomized 704 patients with stage IIIC or IV BRAF V600E or V600K mutation–positive melanoma to first-line therapy with twice-daily dabrafenib 150 mg plus daily trametinib 2 mg or twice-daily vemurafenib 960 mg.

The study sponsor, GlaxoSmithKline, gained accelerated approval in the United States in January 2014 for use of combination dabrafenib and trametinib in unresectable BRAF V600E or V600K mutation–positive melanoma based on positive response data.

The strategy of up-front BRAF and MEK inhibition in BRAF-mutant unresectable disease was supported by data presented in the same session from the coBRIM study, where treatment with vemurafenib and the investigational MEK inhibitor cobimetinib improved progression-free survival, response rates, and overall survival, although the overall survival data are immature. Listen to our interview with coBRIM study author Dr. Grant McArthur.

Dr. Christian Blank, from the Netherlands Cancer Institute in Amsterdam, who was invited to discuss both studies, commented that the combinations used in COMBI-v and coBRIM had similar toxicity to that of single-agent treatment, and that if mature data confirm the presented observations, combined BRAF and MEK inhibition is the new standard therapy for patients with BRAF V600 melanoma.

In COMBI-v, patients receiving dabrafenib plus trametinib, as compared with vemurafenib alone, had more pyrexia (53% vs. 21%), chills (31% vs. 8%), and decreases in ejection fraction (8% vs. 0%), although the latter was easily reversible without sequelae, Dr. Robert stressed. The addition of a MEK inhibitor, however, reduced BRAF inhibitor–related adverse skin events such as cutaneous squamous cell carcinoma and keratoacanthoma (1% vs. 18%), as well as photosensitivity (4% vs. 36%).

GlaxoSmithKline funded the study. Dr. Robert reported serving as a consultant to GlaxoSmithKline, Roche, Bristol-Myers Squibb, Amgen, Novartis, and Merck. Dr. Blank disclosed an advisory role with GSK, Roche, BMS, MSD, and Novartis, honoraria from GSK, Roche, BMS, and MSD, and a research grant from Novartis.

pwendling@frontlinemedcom.com

MADRID – More complete blockade of the MAP kinase pathway with both a BRAF and MEK inhibitor decreased the risk of death by one-third among patients with advanced BRAF mutation–positive melanoma in the phase III COMBI-v study.

After a median follow-up of 10-11 months, the primary endpoint of overall survival was 17.2 months with the BRAF inhibitor vemurafenib (Zelboraf) alone, but had not been reached with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) (hazard ratio, 0.69; P = .005).

Patrice Wendling/Frontline Medical News

“This combination has met all the endpoints that were looked for, and I’d like to remind you that we compared this combination to an already very active drug,” study author Dr. Caroline Robert, head of dermatology at the Institut Gustave Roussy in Paris, said during a presidential session at the European Society for Medical Oncology Congress.

Patients in the combination arm had significantly better median progression-free survival than those given vemurafenib monotherapy (11.4 vs. 7.3 months; HR, 0.56; P < .001), as well as higher response rates (64% vs. 51%; P < .001), more complete responses (13% vs. 8%), and a longer duration of response (13.8 vs. 7.5 months).

COMBI-v was stopped early for efficacy at the interim analysis, which de facto became the final overall survival analysis presented by Dr. Robert.

The study evenly randomized 704 patients with stage IIIC or IV BRAF V600E or V600K mutation–positive melanoma to first-line therapy with twice-daily dabrafenib 150 mg plus daily trametinib 2 mg or twice-daily vemurafenib 960 mg.

The study sponsor, GlaxoSmithKline, gained accelerated approval in the United States in January 2014 for use of combination dabrafenib and trametinib in unresectable BRAF V600E or V600K mutation–positive melanoma based on positive response data.

The strategy of up-front BRAF and MEK inhibition in BRAF-mutant unresectable disease was supported by data presented in the same session from the coBRIM study, where treatment with vemurafenib and the investigational MEK inhibitor cobimetinib improved progression-free survival, response rates, and overall survival, although the overall survival data are immature. Listen to our interview with coBRIM study author Dr. Grant McArthur.

Dr. Christian Blank, from the Netherlands Cancer Institute in Amsterdam, who was invited to discuss both studies, commented that the combinations used in COMBI-v and coBRIM had similar toxicity to that of single-agent treatment, and that if mature data confirm the presented observations, combined BRAF and MEK inhibition is the new standard therapy for patients with BRAF V600 melanoma.

In COMBI-v, patients receiving dabrafenib plus trametinib, as compared with vemurafenib alone, had more pyrexia (53% vs. 21%), chills (31% vs. 8%), and decreases in ejection fraction (8% vs. 0%), although the latter was easily reversible without sequelae, Dr. Robert stressed. The addition of a MEK inhibitor, however, reduced BRAF inhibitor–related adverse skin events such as cutaneous squamous cell carcinoma and keratoacanthoma (1% vs. 18%), as well as photosensitivity (4% vs. 36%).

GlaxoSmithKline funded the study. Dr. Robert reported serving as a consultant to GlaxoSmithKline, Roche, Bristol-Myers Squibb, Amgen, Novartis, and Merck. Dr. Blank disclosed an advisory role with GSK, Roche, BMS, MSD, and Novartis, honoraria from GSK, Roche, BMS, and MSD, and a research grant from Novartis.

pwendling@frontlinemedcom.com

MADRID – More complete blockade of the MAP kinase pathway with both a BRAF and MEK inhibitor decreased the risk of death by one-third among patients with advanced BRAF mutation–positive melanoma in the phase III COMBI-v study.

After a median follow-up of 10-11 months, the primary endpoint of overall survival was 17.2 months with the BRAF inhibitor vemurafenib (Zelboraf) alone, but had not been reached with the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) (hazard ratio, 0.69; P = .005).

Patrice Wendling/Frontline Medical News

“This combination has met all the endpoints that were looked for, and I’d like to remind you that we compared this combination to an already very active drug,” study author Dr. Caroline Robert, head of dermatology at the Institut Gustave Roussy in Paris, said during a presidential session at the European Society for Medical Oncology Congress.

Patients in the combination arm had significantly better median progression-free survival than those given vemurafenib monotherapy (11.4 vs. 7.3 months; HR, 0.56; P < .001), as well as higher response rates (64% vs. 51%; P < .001), more complete responses (13% vs. 8%), and a longer duration of response (13.8 vs. 7.5 months).

COMBI-v was stopped early for efficacy at the interim analysis, which de facto became the final overall survival analysis presented by Dr. Robert.

The study evenly randomized 704 patients with stage IIIC or IV BRAF V600E or V600K mutation–positive melanoma to first-line therapy with twice-daily dabrafenib 150 mg plus daily trametinib 2 mg or twice-daily vemurafenib 960 mg.

The study sponsor, GlaxoSmithKline, gained accelerated approval in the United States in January 2014 for use of combination dabrafenib and trametinib in unresectable BRAF V600E or V600K mutation–positive melanoma based on positive response data.

The strategy of up-front BRAF and MEK inhibition in BRAF-mutant unresectable disease was supported by data presented in the same session from the coBRIM study, where treatment with vemurafenib and the investigational MEK inhibitor cobimetinib improved progression-free survival, response rates, and overall survival, although the overall survival data are immature. Listen to our interview with coBRIM study author Dr. Grant McArthur.

Dr. Christian Blank, from the Netherlands Cancer Institute in Amsterdam, who was invited to discuss both studies, commented that the combinations used in COMBI-v and coBRIM had similar toxicity to that of single-agent treatment, and that if mature data confirm the presented observations, combined BRAF and MEK inhibition is the new standard therapy for patients with BRAF V600 melanoma.

In COMBI-v, patients receiving dabrafenib plus trametinib, as compared with vemurafenib alone, had more pyrexia (53% vs. 21%), chills (31% vs. 8%), and decreases in ejection fraction (8% vs. 0%), although the latter was easily reversible without sequelae, Dr. Robert stressed. The addition of a MEK inhibitor, however, reduced BRAF inhibitor–related adverse skin events such as cutaneous squamous cell carcinoma and keratoacanthoma (1% vs. 18%), as well as photosensitivity (4% vs. 36%).

GlaxoSmithKline funded the study. Dr. Robert reported serving as a consultant to GlaxoSmithKline, Roche, Bristol-Myers Squibb, Amgen, Novartis, and Merck. Dr. Blank disclosed an advisory role with GSK, Roche, BMS, MSD, and Novartis, honoraria from GSK, Roche, BMS, and MSD, and a research grant from Novartis.

pwendling@frontlinemedcom.com

PHILADELPHIA – Every recurrence of Clostridium difficile was associated with a hospital admission in 1 in 4 cases and a complication in 1 in 15 cases, according to a retrospective Canadian cohort study.

“We do have therapeutic options targeted specifically at recurrence, namely fecal transplant, fidaxomicin, and monoclonal antibodies,” study author Dr. Caroline Sheitoyan-Pesant said at Infectious Diseases Week 2014. “But the problem with these approaches is they are either laborious, costly, or unavailable, which is why we felt the need to clarify the burden of multiple recurrences in order to use those options more wisely in the future.”

Dr. Sheitoyan-Pesant and her colleagues at the University of Sherbrooke used a positive cytotoxin and/or ICD-9 CM/ICD-10 code to identified 1,527 episodes of C. difficile infection (CDI) among 1,442 adults living in 1998-2013 in the Sherbrooke area of Quebec, Canada.

Recurrence was defined as the reappearance of diarrhea leading to treatment between 14 to 60 days following the previous episode, with or without microbiologic or endoscopic supportive evidence.

Initial CDI was community acquired in 45% of cases, and 63% of patients were aged at least 65 years. 

Among 1,418 patients who did not die within 14 days of diagnosis, 25% (354) had a first recurrence, Dr Sheitoyan-Pesant said.

Subsequent recurrence rates were 38.3% (128 of 334) for the second recurrence, 29% (35 of 121) for the third, and 27.3% (9 of 33) for the fourth, with numbers quite small for the fifth (62.5%; 5 of 8), and sixth 25% (1 of 4) recurrences.

“Recurrence rates are probably more stable over time than what we used to think before and probably between 25% and 38%,” she said.

When examined by year of diagnosis, the risk of having a first recurrence was 12% during 1998-2002. After the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain, however, first recurrence rates jumped to 32% in 2003-2005, 20% in 2006-2009, and 31% in 2010-2013.

The NAP1 strain has been shown to be a predictor of severe disease, severe outcome, and death in CDI (Clin. Infect. Dis. 2014;58:1394-400).

The initial CDI episode was severe in 47% of the 1,527 episodes, driven mostly by elevated white blood cell counts. The severity rate went down with each recurrence, which was not the case for complicated episodes, as those rates were stable over time, Dr. Sheitoyan-Pesant said.

The 30-day mortality rate was also stable over time, at 11% for the initial CDI episode and 7%-8% for recurrences.

The study was supported by Cubist as part of an investigator-initiated research study. Dr. Sheitoyan-Pesant reported having no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA – Every recurrence of Clostridium difficile was associated with a hospital admission in 1 in 4 cases and a complication in 1 in 15 cases, according to a retrospective Canadian cohort study.

“We do have therapeutic options targeted specifically at recurrence, namely fecal transplant, fidaxomicin, and monoclonal antibodies,” study author Dr. Caroline Sheitoyan-Pesant said at Infectious Diseases Week 2014. “But the problem with these approaches is they are either laborious, costly, or unavailable, which is why we felt the need to clarify the burden of multiple recurrences in order to use those options more wisely in the future.”

Dr. Sheitoyan-Pesant and her colleagues at the University of Sherbrooke used a positive cytotoxin and/or ICD-9 CM/ICD-10 code to identified 1,527 episodes of C. difficile infection (CDI) among 1,442 adults living in 1998-2013 in the Sherbrooke area of Quebec, Canada.

Recurrence was defined as the reappearance of diarrhea leading to treatment between 14 to 60 days following the previous episode, with or without microbiologic or endoscopic supportive evidence.

Initial CDI was community acquired in 45% of cases, and 63% of patients were aged at least 65 years. 

Among 1,418 patients who did not die within 14 days of diagnosis, 25% (354) had a first recurrence, Dr Sheitoyan-Pesant said.

Subsequent recurrence rates were 38.3% (128 of 334) for the second recurrence, 29% (35 of 121) for the third, and 27.3% (9 of 33) for the fourth, with numbers quite small for the fifth (62.5%; 5 of 8), and sixth 25% (1 of 4) recurrences.

“Recurrence rates are probably more stable over time than what we used to think before and probably between 25% and 38%,” she said.

When examined by year of diagnosis, the risk of having a first recurrence was 12% during 1998-2002. After the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain, however, first recurrence rates jumped to 32% in 2003-2005, 20% in 2006-2009, and 31% in 2010-2013.

The NAP1 strain has been shown to be a predictor of severe disease, severe outcome, and death in CDI (Clin. Infect. Dis. 2014;58:1394-400).

The initial CDI episode was severe in 47% of the 1,527 episodes, driven mostly by elevated white blood cell counts. The severity rate went down with each recurrence, which was not the case for complicated episodes, as those rates were stable over time, Dr. Sheitoyan-Pesant said.

The 30-day mortality rate was also stable over time, at 11% for the initial CDI episode and 7%-8% for recurrences.

The study was supported by Cubist as part of an investigator-initiated research study. Dr. Sheitoyan-Pesant reported having no financial disclosures.

pwendling@frontlinemedcom.com

PHILADELPHIA – Every recurrence of Clostridium difficile was associated with a hospital admission in 1 in 4 cases and a complication in 1 in 15 cases, according to a retrospective Canadian cohort study.

“We do have therapeutic options targeted specifically at recurrence, namely fecal transplant, fidaxomicin, and monoclonal antibodies,” study author Dr. Caroline Sheitoyan-Pesant said at Infectious Diseases Week 2014. “But the problem with these approaches is they are either laborious, costly, or unavailable, which is why we felt the need to clarify the burden of multiple recurrences in order to use those options more wisely in the future.”

Dr. Sheitoyan-Pesant and her colleagues at the University of Sherbrooke used a positive cytotoxin and/or ICD-9 CM/ICD-10 code to identified 1,527 episodes of C. difficile infection (CDI) among 1,442 adults living in 1998-2013 in the Sherbrooke area of Quebec, Canada.

Recurrence was defined as the reappearance of diarrhea leading to treatment between 14 to 60 days following the previous episode, with or without microbiologic or endoscopic supportive evidence.

Initial CDI was community acquired in 45% of cases, and 63% of patients were aged at least 65 years. 

Among 1,418 patients who did not die within 14 days of diagnosis, 25% (354) had a first recurrence, Dr Sheitoyan-Pesant said.

Subsequent recurrence rates were 38.3% (128 of 334) for the second recurrence, 29% (35 of 121) for the third, and 27.3% (9 of 33) for the fourth, with numbers quite small for the fifth (62.5%; 5 of 8), and sixth 25% (1 of 4) recurrences.

“Recurrence rates are probably more stable over time than what we used to think before and probably between 25% and 38%,” she said.

When examined by year of diagnosis, the risk of having a first recurrence was 12% during 1998-2002. After the emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain, however, first recurrence rates jumped to 32% in 2003-2005, 20% in 2006-2009, and 31% in 2010-2013.

The NAP1 strain has been shown to be a predictor of severe disease, severe outcome, and death in CDI (Clin. Infect. Dis. 2014;58:1394-400).

The initial CDI episode was severe in 47% of the 1,527 episodes, driven mostly by elevated white blood cell counts. The severity rate went down with each recurrence, which was not the case for complicated episodes, as those rates were stable over time, Dr. Sheitoyan-Pesant said.

The 30-day mortality rate was also stable over time, at 11% for the initial CDI episode and 7%-8% for recurrences.

The study was supported by Cubist as part of an investigator-initiated research study. Dr. Sheitoyan-Pesant reported having no financial disclosures.

pwendling@frontlinemedcom.com