Miriam E. Tucker

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

WASHINGTON  – Early use of antiretroviral therapy significantly reduced the incidence of clinical events – including tuberculosis and AIDS-defining events – among HIV positive adults in a large multinational trial.

"Overall, our interpretation was that there is a marked clinical benefit in terms of reduced clinical events by starting antiretroviral therapy early," Dr. Mina C. Hosseinipour said in a press briefing held during the meeting.

The data are the latest from the landmark HIV Prevention Trials Network study number 052 (HPTN 052), which previously had shown that use of antiretroviral therapy (ART) early – when CD4 counts were between 350 and 550 cells/mm³ – in the HIV-positive partners of a total of 1,763 serodiscordant couples reduced the rate of HIV transmission to the uninfected partner by 96%. It also showed that early ART is associated with a longer time to HIV disease progression and preservation of the immune system over 2 years in the patients themselves (N. Engl. J. Med. 2011;365:493-505).

"So, we think that combined with the preventive benefit, the clinical benefit that one can see from earlier antiretroviral therapy does support earlier antiretroviral initiation" when CD4 counts are between 350 and 550 cells per cubic millimeter, said Dr. Hosseinipour, clinical director of the University of North Carolina Project in Lilongwe, Malawi.

The new analysis, including an additional 3 months of follow-up from the earlier report, focused on clinical end points among those randomized to early vs. later (CD4 count less than 250/mm³ or the onset of AIDS) antiretroviral treatment. The data were presented at the conference by Dr. Beatriz Grinsztejn of Instituto de Pesquisa Clinica Evandro Chagas, Manguinhos, Brazil.

At baseline, the 886 participants in the immediate ART group were similar to the 875 participants in the delayed ART group with regard to gender (about 50/50); two-thirds between the ages of 26 and 40 years. Just over half (54%) were from Africa, and slightly less than a third (30%) from Asia. The rest were from South America. Baseline CD4 counts were 428 cells/mm³ for the delayed ART group and 442 cells/mm³ for the immediate group, and baseline HIV-1 RNA level was 4.4 log10 copies/mL in both groups.

During an overall median follow-up of 2.1 years, 24% (213) patients in the delayed arm initiated ART, at a median of 3.8 years to initiation. Median duration of exposure to ART was 1 year, vs. 2 years in the immediate treatment group.

The specified primary clinical events were death, World Health Organization stage 4 events, tuberculosis, severe bacterial infection, and targeted non-AIDS events, including serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non-AIDS malignancy, and diabetes mellitus.

There were no differences in primary event rates between the two groups during the first year, but by the end of the follow-up period, 9% (77) of the delayed group vs. 6% (57) of the immediate group experienced at least one primary event, for a hazard ratio of 1.37. AIDS-related events occurred in 61 of the 77 delayed-therapy group and 40 of the 57 immediate-therapy group patients. Deaths occurred in 15 and 11, respectively. Non-AIDS events occurred in 9 delayed vs.12 immediate-therapy group patients, including diabetes mellitus in 5 and 4, respectively, Dr. Grinsztejn reported.

There were no significant differences in primary event rates by region, gender, or baseline CD4 count above vs. below 450 cells/mm³, she said.

In a multivariate analysis, factors significantly associated with primary events were age 40 years and older vs. 18-24 years (HR, 2.42), having a greater pretreatment HIV-1 log10 RNA count (1.34/1 log higher), a higher hemoglobin (grade 2 or higher vs. 0/1), and hepatitis B coinfection (1.85 for yes vs. no). In addition, regardless of treatment arm, each 50 CD4 cell higher count was associated with a 10% lower risk of primary events, she reported.

Tuberculosis was significantly more frequent in the delayed treatment group, 4% (34) vs. 2% (17), as were WHO stage 4 events (2% vs. 1%), with chronic herpes simplex being the most common of those (in 8 vs. 2 patients, respectively). Serious bacterial infections were more common among the immediate treatment patients, 2% vs. 1%.

Among the secondary events, herpes zoster, oral candidiasis, and seborrheic dermatitis were the most prevalent, all being more common in the delayed-treatment group, she noted.

Combining all primary and secondary events, the incidence was 29/100 person-years for delayed treatment vs. 25/100 person-years for immediate treatment, a significant difference (P = .02). At the time of primary clinical events, the CD4 count was significantly higher in the immediate-treatment group, compared with the delayed group (502 vs. 351). There was a similar distribution with the secondary events (540 vs. 377). Approximately half of the events in the delayed arm occurred at CD4 cell counts higher than 350, Dr. Grinsztejn noted.

The HPTN 052 study is ongoing. All HIV infected subjects were offered ART and 93% of the index cases are now on it. Retention is 96% among the index cases and 85% for the discordant couples. Still undetermined are the durability of the prevention benefit and the consequences of delayed ART on clinical outcomes over a longer follow-up, she said.

In addition, giving antiretroviral therapy early to HIV-positive patients is cost effective over a 5-year and lifetime horizon, according to a subanalysis of HPTN 052.

Researchers from the Harvard Medical School, Boston, presented the cost-effectiveness analysis on behalf of the HPTN. They analyzed 5-year and lifetime survival and costs in India and South Africa.

To be deemed "very cost effective," early ART had to be less than one times the per capita gross domestic product of each country. To be "cost effective," it would need to be less than three times the gross domestic product (GDP). In South Africa, the per capita GDP was $8,100, and in India it was $1,400.

The cost of ART – whether early or delayed – was higher in South Africa than in India, largely because the costs of care were higher. Early ART for the initially infected patients cost $4,600 over the 5-year horizon in South Africa and $2,300 in India. The lifetime cost for early ART was $18,400 in South Africa, compared with $11,300 in India.

Early ART cost more than delayed ART. But survival was higher with early ART – 93%, compared with 84% for delayed ART in South Africa, for instance – and there was a marked and immediate decrease in transmission for early ART in both India and South Africa, said Dr. Kenneth A. Freedberg, director of the HIV Research Program in the division of general medicine at Massachusetts General Hospital, Boston.

The early therapy also prevented opportunistic infections in South Africa. It was deemed very cost effective in South Africa, at $700/year of life saved in the 5-year time frame, and $1,200/year of life saved over the lifetime.

In India, early ART increased survival also and reduced transmissions of the virus. It was deemed cost effective in that country, at $2,900/year of life saved over the 5-year time frame. The lifetime horizon nudged it up to very cost effective at $1,300/year of life saved.

Increased survival in both countries was a bit of a double-edged sword. Those who lived longer also tended to have more HIV transmissions, Dr. Freedberg explained. Even so, early ART appears to be a winning strategy, he said.

"The clinical data, the behavioral data, the economic data, are converging on the very clear consensus that early antiretroviral therapy is clinically effective for individuals, prevents transmission, and is very cost effective," he said in presenting the abstract.

Dr. Freedberg added that early ART should definitely be given to serodiscordant couples.

In addition, he said, "We’re moving toward the situation where the data support early antiretroviral therapy for anybody infected."

The HIV Prevention Trials Network is funded by the National Institute of Allergy and Infectious Diseases. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences; GlaxoSmithKline/ViiV Healthcare, and Merck.

Dr. Grinsztejn stated that she has no additional disclosures.

Alicia Ault, a medical media reporter for IMNG, contributed to this article.

An experimental first-line chemotherapy regimen that included pemetrexed did not improve overall survival compared with standard paclitaxel-based treatment in a phase III randomized, open-label study of more than 900 patients with late-stage lung cancer.

The experimental regimen did improve progression-free survival, a secondary end point of the study called POINTBREAK by Eli Lilly.

Courtesy ASTRO

"The fact that there was no improvement in survival with the experimental regimen was disappointing, but these findings are important as we continue to navigate ways to improve survival for this devastating disease," lead author Dr. Jyoti D. Patel said during a press briefing at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Funded by Lilly, the phase III study compared an experimental regimen of pemetrexed (Alimta) plus carboplatin plus bevacizumab (Avastin) followed by maintenance pemetrexed plus bevacizumab (the Pem arm) with a Food and Drug Administration–approved regimen of paclitaxel plus carboplatin plus bevacizumab followed by maintenance bevacizumab (the Pac Arm) in previously untreated patients with stage IIIB or IV nonsquamous non–small cell lung cancer (NS-NSCLC).

A total of 939 such patients who had Eastern Oncology Cooperative Group performance status of 0-1 were randomized. Patients in the experimental arm received pemetrexed (500 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg) along with folic acid, vitamin B₁₂ and dexamethasone supplementation. The control group received paclitaxel (200 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg), and dexamethasone, diphenhydramine, and cimetidine or ranitidine premedications.

Both regimens were given every 3 weeks for up to four cycles. Patients who continued without progressive disease received maintenance pemetrexed plus bevacizumab (Pem Arm) or maintenance bevacizumab (Pac Arm).

The overall patient population had a median age of 64.7 years, was 53.2% male, and 85.7% white. Nearly all, 90.0%, had stage IV NSCLC, and 79.2% had adenocarcinoma. Only 11.6% had never smoked.

Median overall survival – the primary end point – was 12.6 months in the experimental group (Pem arm) and 13.4 months for the control group (Pac arm), a nonsignificant difference (hazard ratio, 1.00; P = .949. The 1-year survival rates were 52.7% and 54.1%, respectively; the 2-year rates were 24.4% and 21.2%, respectively.

Median progression-free survival was significantly longer for the Pem arm: 6.0 versus 5.6 months (HR, 0.83; P = .012. The overall response rates were 34.1% with pemetrexed and 33.0% with paclitaxel; the disease control rates were 65.9% and 69.8%, respectively, Dr. Patel reported.

The pemetrexed arm has significantly more study drug-related grade 3/4 anemia (14.5% vs. 2.7%), thrombocytopenia (23.3% vs. 5.6%) and fatigue (10.9% vs. 5.0%). The paclitaxel arm had significantly more grade 3/4 neutropenia (40.6% vs. 25.8%), febrile neutropenia (4.1% vs. 1.4%), sensory neuropathy (4.1% vs. 0) and complete (grade 2) alopecia (21.4 % vs. 1.1%). These event rates are similar to those seen in previous trials, she noted.

Hemorrhage – either gastrointestinal or pulmonary and thromboembolic events were infrequent and similar between arms. There were very few grade 5 events, she said.

Study drug-related discontinuations due to severe adverse events (2.7% vs. 3.6%), adverse events (10.4% vs. 9.0%), and study drug-related deaths due to adverse events (1.8% vs. 2.3%) were similar between the two groups (Pem arm vs. Pac arm, respectively).

"It is important to note that both regimens demonstrated tolerability, although their toxicities differed. These differences can be important for our patients," said Dr. Patel of the department of medicine-hematology/oncology at Northwestern University, Chicago.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago

Dr. Patel received a research grant from Eli Lilly for this study. Several of her coauthors had ties to Lilly and other companies including Genentech, Pfizer, and GlaxoSmithKline.

An experimental first-line chemotherapy regimen that included pemetrexed did not improve overall survival compared with standard paclitaxel-based treatment in a phase III randomized, open-label study of more than 900 patients with late-stage lung cancer.

The experimental regimen did improve progression-free survival, a secondary end point of the study called POINTBREAK by Eli Lilly.

Courtesy ASTRO

"The fact that there was no improvement in survival with the experimental regimen was disappointing, but these findings are important as we continue to navigate ways to improve survival for this devastating disease," lead author Dr. Jyoti D. Patel said during a press briefing at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Funded by Lilly, the phase III study compared an experimental regimen of pemetrexed (Alimta) plus carboplatin plus bevacizumab (Avastin) followed by maintenance pemetrexed plus bevacizumab (the Pem arm) with a Food and Drug Administration–approved regimen of paclitaxel plus carboplatin plus bevacizumab followed by maintenance bevacizumab (the Pac Arm) in previously untreated patients with stage IIIB or IV nonsquamous non–small cell lung cancer (NS-NSCLC).

A total of 939 such patients who had Eastern Oncology Cooperative Group performance status of 0-1 were randomized. Patients in the experimental arm received pemetrexed (500 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg) along with folic acid, vitamin B₁₂ and dexamethasone supplementation. The control group received paclitaxel (200 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg), and dexamethasone, diphenhydramine, and cimetidine or ranitidine premedications.

Both regimens were given every 3 weeks for up to four cycles. Patients who continued without progressive disease received maintenance pemetrexed plus bevacizumab (Pem Arm) or maintenance bevacizumab (Pac Arm).

The overall patient population had a median age of 64.7 years, was 53.2% male, and 85.7% white. Nearly all, 90.0%, had stage IV NSCLC, and 79.2% had adenocarcinoma. Only 11.6% had never smoked.

Median overall survival – the primary end point – was 12.6 months in the experimental group (Pem arm) and 13.4 months for the control group (Pac arm), a nonsignificant difference (hazard ratio, 1.00; P = .949. The 1-year survival rates were 52.7% and 54.1%, respectively; the 2-year rates were 24.4% and 21.2%, respectively.

Median progression-free survival was significantly longer for the Pem arm: 6.0 versus 5.6 months (HR, 0.83; P = .012. The overall response rates were 34.1% with pemetrexed and 33.0% with paclitaxel; the disease control rates were 65.9% and 69.8%, respectively, Dr. Patel reported.

The pemetrexed arm has significantly more study drug-related grade 3/4 anemia (14.5% vs. 2.7%), thrombocytopenia (23.3% vs. 5.6%) and fatigue (10.9% vs. 5.0%). The paclitaxel arm had significantly more grade 3/4 neutropenia (40.6% vs. 25.8%), febrile neutropenia (4.1% vs. 1.4%), sensory neuropathy (4.1% vs. 0) and complete (grade 2) alopecia (21.4 % vs. 1.1%). These event rates are similar to those seen in previous trials, she noted.

Hemorrhage – either gastrointestinal or pulmonary and thromboembolic events were infrequent and similar between arms. There were very few grade 5 events, she said.

Study drug-related discontinuations due to severe adverse events (2.7% vs. 3.6%), adverse events (10.4% vs. 9.0%), and study drug-related deaths due to adverse events (1.8% vs. 2.3%) were similar between the two groups (Pem arm vs. Pac arm, respectively).

"It is important to note that both regimens demonstrated tolerability, although their toxicities differed. These differences can be important for our patients," said Dr. Patel of the department of medicine-hematology/oncology at Northwestern University, Chicago.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago

Dr. Patel received a research grant from Eli Lilly for this study. Several of her coauthors had ties to Lilly and other companies including Genentech, Pfizer, and GlaxoSmithKline.

An experimental first-line chemotherapy regimen that included pemetrexed did not improve overall survival compared with standard paclitaxel-based treatment in a phase III randomized, open-label study of more than 900 patients with late-stage lung cancer.

The experimental regimen did improve progression-free survival, a secondary end point of the study called POINTBREAK by Eli Lilly.

Courtesy ASTRO

"The fact that there was no improvement in survival with the experimental regimen was disappointing, but these findings are important as we continue to navigate ways to improve survival for this devastating disease," lead author Dr. Jyoti D. Patel said during a press briefing at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Funded by Lilly, the phase III study compared an experimental regimen of pemetrexed (Alimta) plus carboplatin plus bevacizumab (Avastin) followed by maintenance pemetrexed plus bevacizumab (the Pem arm) with a Food and Drug Administration–approved regimen of paclitaxel plus carboplatin plus bevacizumab followed by maintenance bevacizumab (the Pac Arm) in previously untreated patients with stage IIIB or IV nonsquamous non–small cell lung cancer (NS-NSCLC).

A total of 939 such patients who had Eastern Oncology Cooperative Group performance status of 0-1 were randomized. Patients in the experimental arm received pemetrexed (500 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg) along with folic acid, vitamin B₁₂ and dexamethasone supplementation. The control group received paclitaxel (200 mg/m²) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg), and dexamethasone, diphenhydramine, and cimetidine or ranitidine premedications.

Both regimens were given every 3 weeks for up to four cycles. Patients who continued without progressive disease received maintenance pemetrexed plus bevacizumab (Pem Arm) or maintenance bevacizumab (Pac Arm).

The overall patient population had a median age of 64.7 years, was 53.2% male, and 85.7% white. Nearly all, 90.0%, had stage IV NSCLC, and 79.2% had adenocarcinoma. Only 11.6% had never smoked.

Median overall survival – the primary end point – was 12.6 months in the experimental group (Pem arm) and 13.4 months for the control group (Pac arm), a nonsignificant difference (hazard ratio, 1.00; P = .949. The 1-year survival rates were 52.7% and 54.1%, respectively; the 2-year rates were 24.4% and 21.2%, respectively.

Median progression-free survival was significantly longer for the Pem arm: 6.0 versus 5.6 months (HR, 0.83; P = .012. The overall response rates were 34.1% with pemetrexed and 33.0% with paclitaxel; the disease control rates were 65.9% and 69.8%, respectively, Dr. Patel reported.

The pemetrexed arm has significantly more study drug-related grade 3/4 anemia (14.5% vs. 2.7%), thrombocytopenia (23.3% vs. 5.6%) and fatigue (10.9% vs. 5.0%). The paclitaxel arm had significantly more grade 3/4 neutropenia (40.6% vs. 25.8%), febrile neutropenia (4.1% vs. 1.4%), sensory neuropathy (4.1% vs. 0) and complete (grade 2) alopecia (21.4 % vs. 1.1%). These event rates are similar to those seen in previous trials, she noted.

Hemorrhage – either gastrointestinal or pulmonary and thromboembolic events were infrequent and similar between arms. There were very few grade 5 events, she said.

Study drug-related discontinuations due to severe adverse events (2.7% vs. 3.6%), adverse events (10.4% vs. 9.0%), and study drug-related deaths due to adverse events (1.8% vs. 2.3%) were similar between the two groups (Pem arm vs. Pac arm, respectively).

"It is important to note that both regimens demonstrated tolerability, although their toxicities differed. These differences can be important for our patients," said Dr. Patel of the department of medicine-hematology/oncology at Northwestern University, Chicago.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago

Dr. Patel received a research grant from Eli Lilly for this study. Several of her coauthors had ties to Lilly and other companies including Genentech, Pfizer, and GlaxoSmithKline.

Prophylactic cranial irradiation reduced the 5-year rate of brain metastases, but did not improve overall survival in a randomized trial that evaluated 340 patients without disease progression following potentially curative treatment for locally advanced non–small cell lung cancer.

The findings provide important confirmatory information regarding the effectiveness of prophylactic cranial irradiation (PCI) in decreasing the rate of brain failures, Dr. Elizabeth Gore said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Courtesy ASTRO

The trial closed early because of slow patient accrual, however, and did not enroll enough patients to answer the primary question: whether PCI improves overall survival in patients with stage III NSCLC.

"I’d like to emphasize the need for participation in clinical trials. This is particularly important in lung cancer, which is understudied" despite its being the leading cause of cancer death in the United States, said Dr. Gore, professor of radiation oncology at the Medical College of Wisconsin, Milwaukee.

Over a median follow-up of 24.2 months for all patients and 58.6 months for living patients, the 5-year rates of brain metastases were 17.3% for those randomized to receive PCI delivered to 30 Gy in 15 fractions, compared with 26.8% for patients randomized to observation. That difference was statistically significant (P = .009).

However, there were no significant differences in the 5-year rates of survival, (26.1% for PCI and 24.6% for observation), or disease-free survival (18.5% and 14.9%, respectively).

Of the patients with treatment failures, 10% of those receiving PCI and 23% in the observation group experienced failure in the brain initially. Brain metastases (BM) were the only component of first failure in 9.1% and 21.5% of patients with and without PCI, respectively.

On multivariate analysis, PCI was significantly associated with decreased BM, whereas nonsquamous histology was associated with an increased risk of BM. The overall rate of BM in this trial was insufficient for reliable subset analyses by histology, Dr. Gore noted.

"Brain metastasis has a profound impact on patients with lung cancer in terms of quality of life. We need more information to determine which patients are most likely to derive a survival benefit from prophylactic cranial irradiation before this can become a part of standard management," she said.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Dr. Gore and her associates have no financial disclosures.

Prophylactic cranial irradiation reduced the 5-year rate of brain metastases, but did not improve overall survival in a randomized trial that evaluated 340 patients without disease progression following potentially curative treatment for locally advanced non–small cell lung cancer.

The findings provide important confirmatory information regarding the effectiveness of prophylactic cranial irradiation (PCI) in decreasing the rate of brain failures, Dr. Elizabeth Gore said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Courtesy ASTRO

The trial closed early because of slow patient accrual, however, and did not enroll enough patients to answer the primary question: whether PCI improves overall survival in patients with stage III NSCLC.

"I’d like to emphasize the need for participation in clinical trials. This is particularly important in lung cancer, which is understudied" despite its being the leading cause of cancer death in the United States, said Dr. Gore, professor of radiation oncology at the Medical College of Wisconsin, Milwaukee.

Over a median follow-up of 24.2 months for all patients and 58.6 months for living patients, the 5-year rates of brain metastases were 17.3% for those randomized to receive PCI delivered to 30 Gy in 15 fractions, compared with 26.8% for patients randomized to observation. That difference was statistically significant (P = .009).

However, there were no significant differences in the 5-year rates of survival, (26.1% for PCI and 24.6% for observation), or disease-free survival (18.5% and 14.9%, respectively).

Of the patients with treatment failures, 10% of those receiving PCI and 23% in the observation group experienced failure in the brain initially. Brain metastases (BM) were the only component of first failure in 9.1% and 21.5% of patients with and without PCI, respectively.

On multivariate analysis, PCI was significantly associated with decreased BM, whereas nonsquamous histology was associated with an increased risk of BM. The overall rate of BM in this trial was insufficient for reliable subset analyses by histology, Dr. Gore noted.

"Brain metastasis has a profound impact on patients with lung cancer in terms of quality of life. We need more information to determine which patients are most likely to derive a survival benefit from prophylactic cranial irradiation before this can become a part of standard management," she said.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Dr. Gore and her associates have no financial disclosures.

Prophylactic cranial irradiation reduced the 5-year rate of brain metastases, but did not improve overall survival in a randomized trial that evaluated 340 patients without disease progression following potentially curative treatment for locally advanced non–small cell lung cancer.

The findings provide important confirmatory information regarding the effectiveness of prophylactic cranial irradiation (PCI) in decreasing the rate of brain failures, Dr. Elizabeth Gore said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Courtesy ASTRO

The trial closed early because of slow patient accrual, however, and did not enroll enough patients to answer the primary question: whether PCI improves overall survival in patients with stage III NSCLC.

"I’d like to emphasize the need for participation in clinical trials. This is particularly important in lung cancer, which is understudied" despite its being the leading cause of cancer death in the United States, said Dr. Gore, professor of radiation oncology at the Medical College of Wisconsin, Milwaukee.

Over a median follow-up of 24.2 months for all patients and 58.6 months for living patients, the 5-year rates of brain metastases were 17.3% for those randomized to receive PCI delivered to 30 Gy in 15 fractions, compared with 26.8% for patients randomized to observation. That difference was statistically significant (P = .009).

However, there were no significant differences in the 5-year rates of survival, (26.1% for PCI and 24.6% for observation), or disease-free survival (18.5% and 14.9%, respectively).

Of the patients with treatment failures, 10% of those receiving PCI and 23% in the observation group experienced failure in the brain initially. Brain metastases (BM) were the only component of first failure in 9.1% and 21.5% of patients with and without PCI, respectively.

On multivariate analysis, PCI was significantly associated with decreased BM, whereas nonsquamous histology was associated with an increased risk of BM. The overall rate of BM in this trial was insufficient for reliable subset analyses by histology, Dr. Gore noted.

"Brain metastasis has a profound impact on patients with lung cancer in terms of quality of life. We need more information to determine which patients are most likely to derive a survival benefit from prophylactic cranial irradiation before this can become a part of standard management," she said.

The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Dr. Gore and her associates have no financial disclosures.

Median overall survival increased significantly among patients with stage I non–small cell lung cancer over the last decade – in particular, those treated with radiation therapy alone, according to an analysis of the Surveillance, Epidemiology, and End Results database.

The median survival for all treatment groups increased by 27%, from 44 months during 1999-2003 to 56 months during 2004-2008. For those treated with radiation alone – who would likely be the sickest patients since they would not have been considered candidates for surgery – median overall survival improved by 31%, from 16 to 21 months. Both changes were statistically significant (log rank P less than .0001).

Courtesy ASTRO

"Stage I NSCLC [non–small cell lung cancer] patients who receive radiation therapy alone are surviving longer than they used to," Dr. Nirav S. Kapadia said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

A change in the survival of patients treated with surgery could not be detected, as median survival has not yet been reached, he and his coauthors reported.

Until recently, surgery has been the primary treatment for stage I NSCLC. However, as recent advances in radiotherapy (RT) such as stereotactic body radiation therapy have allowed dose escalation with more precise tumor targeting, the use of RT has increased, and outcomes appear to have improved over time, said Dr. Kapadia, a chief resident in the department of radiation oncology at the University of Michigan, Ann Arbor

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database encompasses about 25% of the U.S. population. This study compared SEER data on 27,469 patients with NSCLC treated during 1999-2003 with data from 26,195 patients treated during 2004-2008.

During 1999-2003, 64% of patients were treated with primary surgery, 14% received RT alone, 20% had neither treatment, and 2% had unknown treatment. In the later era, 70% of patients underwent primary surgery, 13% received primary RT, 16% had neither surgery nor RT, and 1% had unknown treatment.

The proportion receiving surgery alone increased from 60% to 67% during the two time periods. Thus, the rates of surgery increased from the earlier to the later period, but there was no significant difference in the number of patients who received radiotherapy, either as an adjunct to surgery or as definitive therapy, noted Dr. Kapadia.

He expressed concern about the significant proportion of patients – 20% in the earlier period and 16% in the later – who did not receive surgery or radiation. "At least 16% of patients are still not getting the care that they need – care that could save their lives. We must identify the barriers to treatment so that every patient has hope for a cancer cure," he said in a statement.

For the entire study period, factors significantly associated with higher risk of death after primary RT or surgery included age, African American race, large cell or squamous histology, and being unmarried. Significant protective factors included female sex and race listed as "other."

Dr. Kapadia noted that RT is advantageous in that it is noninvasive and is done on an outpatient basis. Moreover, local control rates with radiotherapy among patients who are too sick to undergo surgery are now approaching those of surgery.

Ongoing "coin flip" studies are currently comparing outcomes of radiation versus surgery in patients who would otherwise be fit for surgery. "Those are going to be very exciting studies. ... But for right now I would say surgery is still the preferred modality, with a large body of evidence to support that statement," he said.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Median overall survival increased significantly among patients with stage I non–small cell lung cancer over the last decade – in particular, those treated with radiation therapy alone, according to an analysis of the Surveillance, Epidemiology, and End Results database.

The median survival for all treatment groups increased by 27%, from 44 months during 1999-2003 to 56 months during 2004-2008. For those treated with radiation alone – who would likely be the sickest patients since they would not have been considered candidates for surgery – median overall survival improved by 31%, from 16 to 21 months. Both changes were statistically significant (log rank P less than .0001).

Courtesy ASTRO

"Stage I NSCLC [non–small cell lung cancer] patients who receive radiation therapy alone are surviving longer than they used to," Dr. Nirav S. Kapadia said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

A change in the survival of patients treated with surgery could not be detected, as median survival has not yet been reached, he and his coauthors reported.

Until recently, surgery has been the primary treatment for stage I NSCLC. However, as recent advances in radiotherapy (RT) such as stereotactic body radiation therapy have allowed dose escalation with more precise tumor targeting, the use of RT has increased, and outcomes appear to have improved over time, said Dr. Kapadia, a chief resident in the department of radiation oncology at the University of Michigan, Ann Arbor

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database encompasses about 25% of the U.S. population. This study compared SEER data on 27,469 patients with NSCLC treated during 1999-2003 with data from 26,195 patients treated during 2004-2008.

During 1999-2003, 64% of patients were treated with primary surgery, 14% received RT alone, 20% had neither treatment, and 2% had unknown treatment. In the later era, 70% of patients underwent primary surgery, 13% received primary RT, 16% had neither surgery nor RT, and 1% had unknown treatment.

The proportion receiving surgery alone increased from 60% to 67% during the two time periods. Thus, the rates of surgery increased from the earlier to the later period, but there was no significant difference in the number of patients who received radiotherapy, either as an adjunct to surgery or as definitive therapy, noted Dr. Kapadia.

He expressed concern about the significant proportion of patients – 20% in the earlier period and 16% in the later – who did not receive surgery or radiation. "At least 16% of patients are still not getting the care that they need – care that could save their lives. We must identify the barriers to treatment so that every patient has hope for a cancer cure," he said in a statement.

For the entire study period, factors significantly associated with higher risk of death after primary RT or surgery included age, African American race, large cell or squamous histology, and being unmarried. Significant protective factors included female sex and race listed as "other."

Dr. Kapadia noted that RT is advantageous in that it is noninvasive and is done on an outpatient basis. Moreover, local control rates with radiotherapy among patients who are too sick to undergo surgery are now approaching those of surgery.

Ongoing "coin flip" studies are currently comparing outcomes of radiation versus surgery in patients who would otherwise be fit for surgery. "Those are going to be very exciting studies. ... But for right now I would say surgery is still the preferred modality, with a large body of evidence to support that statement," he said.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Median overall survival increased significantly among patients with stage I non–small cell lung cancer over the last decade – in particular, those treated with radiation therapy alone, according to an analysis of the Surveillance, Epidemiology, and End Results database.

The median survival for all treatment groups increased by 27%, from 44 months during 1999-2003 to 56 months during 2004-2008. For those treated with radiation alone – who would likely be the sickest patients since they would not have been considered candidates for surgery – median overall survival improved by 31%, from 16 to 21 months. Both changes were statistically significant (log rank P less than .0001).

Courtesy ASTRO

"Stage I NSCLC [non–small cell lung cancer] patients who receive radiation therapy alone are surviving longer than they used to," Dr. Nirav S. Kapadia said in a press briefing from the Chicago Multidisciplinary Symposium in Thoracic Oncology.

A change in the survival of patients treated with surgery could not be detected, as median survival has not yet been reached, he and his coauthors reported.

Until recently, surgery has been the primary treatment for stage I NSCLC. However, as recent advances in radiotherapy (RT) such as stereotactic body radiation therapy have allowed dose escalation with more precise tumor targeting, the use of RT has increased, and outcomes appear to have improved over time, said Dr. Kapadia, a chief resident in the department of radiation oncology at the University of Michigan, Ann Arbor

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database encompasses about 25% of the U.S. population. This study compared SEER data on 27,469 patients with NSCLC treated during 1999-2003 with data from 26,195 patients treated during 2004-2008.

During 1999-2003, 64% of patients were treated with primary surgery, 14% received RT alone, 20% had neither treatment, and 2% had unknown treatment. In the later era, 70% of patients underwent primary surgery, 13% received primary RT, 16% had neither surgery nor RT, and 1% had unknown treatment.

The proportion receiving surgery alone increased from 60% to 67% during the two time periods. Thus, the rates of surgery increased from the earlier to the later period, but there was no significant difference in the number of patients who received radiotherapy, either as an adjunct to surgery or as definitive therapy, noted Dr. Kapadia.

He expressed concern about the significant proportion of patients – 20% in the earlier period and 16% in the later – who did not receive surgery or radiation. "At least 16% of patients are still not getting the care that they need – care that could save their lives. We must identify the barriers to treatment so that every patient has hope for a cancer cure," he said in a statement.

For the entire study period, factors significantly associated with higher risk of death after primary RT or surgery included age, African American race, large cell or squamous histology, and being unmarried. Significant protective factors included female sex and race listed as "other."

Dr. Kapadia noted that RT is advantageous in that it is noninvasive and is done on an outpatient basis. Moreover, local control rates with radiotherapy among patients who are too sick to undergo surgery are now approaching those of surgery.

Ongoing "coin flip" studies are currently comparing outcomes of radiation versus surgery in patients who would otherwise be fit for surgery. "Those are going to be very exciting studies. ... But for right now I would say surgery is still the preferred modality, with a large body of evidence to support that statement," he said.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago.

Trastuzumab, whether given with or without anthracyline-based chemotherapy, was associated with significant increases in heart failure and cardiomyopathy in a large population-based, retrospective cohort study of women treated for breast cancer.

In the "real world" study, which used data from the health maintenance organization Cancer Research Network, the adjusted risk of heart failure (HF) and/or cardiomyopathy increased fourfold among women who received trastuzumab (Herceptin) alone and sevenfold in those who received anthracycline plus trastuzumab, compared with women who received no chemotherapy.

In all, the risk of anthracycline-associated HF/cardiomyopathy among women younger than 65 years was similar to results from randomized clinical trials, while the trastuzumab-associated HF/cardiomyopathy risk – whether administered alone or following an anthracycline – was greater than that previously reported.

"Our results highlight the importance of generalizability in applying clinical trial findings to community settings; although similar to clinical trial results, these population-based results cannot be attributed to any single patient in clinical practice," wrote Erin J. Aiello Bowles of Group Health Research Institute, Seattle, and her associates.

Randomized trials have typically excluded older women and those with major comorbidities, and therefore the association between the two agents and HF/cardiomyopathy in this population is not well understood, Ms. Bowles and her associates noted (J. Natl. Cancer Inst. 2012 Aug. 30 [doi:10.1093/jnci/djs317]).

The current study population comprised 12,500 women diagnosed with incident, invasive breast cancer from Jan. 1, 1999, through Dec. 31, 2007, at eight integrated Cancer Research Network health systems. Women diagnosed with HF/cardiomyopathy prior to breast cancer diagnosis or initiation of chemotherapy were excluded. They had a mean age of 60 years (range, 22-99), and 85.8% were white.

In a median follow-up of 4.4 years, nearly half (46.5%) had received no chemotherapy. Just under a third, 29.6%, had received anthracycline-based chemotherapy alone, 0.9% received trastuzumab-based therapy without anthracycline, 3.5% received anthracycline plus trastuzumab, and 19.5% received other chemotherapy.

Compared with the women who received other chemotherapy or no chemotherapy, the women who received anthracycline alone or anthracycline plus trastuzumab were younger, diagnosed at later stages, had fewer comorbidities, and were slightly more likely to receive radiation therapy. These findings "suggest substantial individualization of adjuvant chemotherapy administration by age and comorbidity in community practice," Ms. Bowles and her associates wrote.

The incidence of HF/cardiomyopathy increased with increasing follow-up time for all of the chemotherapy types, but to a greater degree with trastuzumab. The cumulative HF/cardiomyopathy incidence increased from 1.2% at year 1 to 4.3% at year 5 for the anthracycline recipients, which was similar to the increase from 1.3% to 4.5% for those on other chemotherapies. For those with no chemotherapy, the cumulative incidence rose from 0.9% to 3.1%.

In contrast, the cumulative HF/cardiomyopathy incidence among recipients of anthracycline plus trastuzumab was 6.2% after 1 year of follow-up and continued to increase to 20.1% by 5 years.

Compared with no chemotherapy, the risk of incident HF/cardiomyopathy among all women was statistically significantly increased for anthracycline alone (adjusted hazard ratio, 1.40), trastuzumab without anthracycline (HR, 4.12), anthracycline plus trastuzumab (HR, 7.19), and other chemotherapy (HR, 1.49), the investigators said.

The 5-year cumulative incidence for HF/cardiomyopathy associated with each of the chemotherapies was greater in the older age groups, but the hazard ratios for HF/cardiomyopathy associated with chemotherapy use decreased with increasing age. For example, the hazard ratio for HF/cardiomyopathy associated with anthracycline use alone was statistically significant among women younger than 55 years (HR, 2.52) but not among women 55-64 years (HR, 1.61) or older.

According to Ms. Bowles and her associates, this study demonstrates the importance of observational comparative safety and effectiveness studies in providing complementary data to those obtained in clinical trials. "Observational studies allow for estimation of risks and benefits in community practice, which includes patients who may not be eligible for clinical trials. Clinical trials may provide more relevant estimates for patients who are eligible candidates, but many people are not and still receive these treatments in community practice," they wrote.

This work was supported by the National Cancer Institute through an administrative supplement to the Cancer Research Network. Ms. Bowles did not report any financial disclosures, but one of her coauthors, Dr. Larry A. Allen, has received consulting fees from Amgen, Janssen Scientific Affairs, and the Robert Wood Johnson Foundation.

Trastuzumab, whether given with or without anthracyline-based chemotherapy, was associated with significant increases in heart failure and cardiomyopathy in a large population-based, retrospective cohort study of women treated for breast cancer.

In the "real world" study, which used data from the health maintenance organization Cancer Research Network, the adjusted risk of heart failure (HF) and/or cardiomyopathy increased fourfold among women who received trastuzumab (Herceptin) alone and sevenfold in those who received anthracycline plus trastuzumab, compared with women who received no chemotherapy.

In all, the risk of anthracycline-associated HF/cardiomyopathy among women younger than 65 years was similar to results from randomized clinical trials, while the trastuzumab-associated HF/cardiomyopathy risk – whether administered alone or following an anthracycline – was greater than that previously reported.

"Our results highlight the importance of generalizability in applying clinical trial findings to community settings; although similar to clinical trial results, these population-based results cannot be attributed to any single patient in clinical practice," wrote Erin J. Aiello Bowles of Group Health Research Institute, Seattle, and her associates.

Randomized trials have typically excluded older women and those with major comorbidities, and therefore the association between the two agents and HF/cardiomyopathy in this population is not well understood, Ms. Bowles and her associates noted (J. Natl. Cancer Inst. 2012 Aug. 30 [doi:10.1093/jnci/djs317]).

The current study population comprised 12,500 women diagnosed with incident, invasive breast cancer from Jan. 1, 1999, through Dec. 31, 2007, at eight integrated Cancer Research Network health systems. Women diagnosed with HF/cardiomyopathy prior to breast cancer diagnosis or initiation of chemotherapy were excluded. They had a mean age of 60 years (range, 22-99), and 85.8% were white.

In a median follow-up of 4.4 years, nearly half (46.5%) had received no chemotherapy. Just under a third, 29.6%, had received anthracycline-based chemotherapy alone, 0.9% received trastuzumab-based therapy without anthracycline, 3.5% received anthracycline plus trastuzumab, and 19.5% received other chemotherapy.

Compared with the women who received other chemotherapy or no chemotherapy, the women who received anthracycline alone or anthracycline plus trastuzumab were younger, diagnosed at later stages, had fewer comorbidities, and were slightly more likely to receive radiation therapy. These findings "suggest substantial individualization of adjuvant chemotherapy administration by age and comorbidity in community practice," Ms. Bowles and her associates wrote.

The incidence of HF/cardiomyopathy increased with increasing follow-up time for all of the chemotherapy types, but to a greater degree with trastuzumab. The cumulative HF/cardiomyopathy incidence increased from 1.2% at year 1 to 4.3% at year 5 for the anthracycline recipients, which was similar to the increase from 1.3% to 4.5% for those on other chemotherapies. For those with no chemotherapy, the cumulative incidence rose from 0.9% to 3.1%.

In contrast, the cumulative HF/cardiomyopathy incidence among recipients of anthracycline plus trastuzumab was 6.2% after 1 year of follow-up and continued to increase to 20.1% by 5 years.

Compared with no chemotherapy, the risk of incident HF/cardiomyopathy among all women was statistically significantly increased for anthracycline alone (adjusted hazard ratio, 1.40), trastuzumab without anthracycline (HR, 4.12), anthracycline plus trastuzumab (HR, 7.19), and other chemotherapy (HR, 1.49), the investigators said.

The 5-year cumulative incidence for HF/cardiomyopathy associated with each of the chemotherapies was greater in the older age groups, but the hazard ratios for HF/cardiomyopathy associated with chemotherapy use decreased with increasing age. For example, the hazard ratio for HF/cardiomyopathy associated with anthracycline use alone was statistically significant among women younger than 55 years (HR, 2.52) but not among women 55-64 years (HR, 1.61) or older.

According to Ms. Bowles and her associates, this study demonstrates the importance of observational comparative safety and effectiveness studies in providing complementary data to those obtained in clinical trials. "Observational studies allow for estimation of risks and benefits in community practice, which includes patients who may not be eligible for clinical trials. Clinical trials may provide more relevant estimates for patients who are eligible candidates, but many people are not and still receive these treatments in community practice," they wrote.

This work was supported by the National Cancer Institute through an administrative supplement to the Cancer Research Network. Ms. Bowles did not report any financial disclosures, but one of her coauthors, Dr. Larry A. Allen, has received consulting fees from Amgen, Janssen Scientific Affairs, and the Robert Wood Johnson Foundation.

Trastuzumab, whether given with or without anthracyline-based chemotherapy, was associated with significant increases in heart failure and cardiomyopathy in a large population-based, retrospective cohort study of women treated for breast cancer.

In the "real world" study, which used data from the health maintenance organization Cancer Research Network, the adjusted risk of heart failure (HF) and/or cardiomyopathy increased fourfold among women who received trastuzumab (Herceptin) alone and sevenfold in those who received anthracycline plus trastuzumab, compared with women who received no chemotherapy.

In all, the risk of anthracycline-associated HF/cardiomyopathy among women younger than 65 years was similar to results from randomized clinical trials, while the trastuzumab-associated HF/cardiomyopathy risk – whether administered alone or following an anthracycline – was greater than that previously reported.

"Our results highlight the importance of generalizability in applying clinical trial findings to community settings; although similar to clinical trial results, these population-based results cannot be attributed to any single patient in clinical practice," wrote Erin J. Aiello Bowles of Group Health Research Institute, Seattle, and her associates.

Randomized trials have typically excluded older women and those with major comorbidities, and therefore the association between the two agents and HF/cardiomyopathy in this population is not well understood, Ms. Bowles and her associates noted (J. Natl. Cancer Inst. 2012 Aug. 30 [doi:10.1093/jnci/djs317]).

The current study population comprised 12,500 women diagnosed with incident, invasive breast cancer from Jan. 1, 1999, through Dec. 31, 2007, at eight integrated Cancer Research Network health systems. Women diagnosed with HF/cardiomyopathy prior to breast cancer diagnosis or initiation of chemotherapy were excluded. They had a mean age of 60 years (range, 22-99), and 85.8% were white.

In a median follow-up of 4.4 years, nearly half (46.5%) had received no chemotherapy. Just under a third, 29.6%, had received anthracycline-based chemotherapy alone, 0.9% received trastuzumab-based therapy without anthracycline, 3.5% received anthracycline plus trastuzumab, and 19.5% received other chemotherapy.

Compared with the women who received other chemotherapy or no chemotherapy, the women who received anthracycline alone or anthracycline plus trastuzumab were younger, diagnosed at later stages, had fewer comorbidities, and were slightly more likely to receive radiation therapy. These findings "suggest substantial individualization of adjuvant chemotherapy administration by age and comorbidity in community practice," Ms. Bowles and her associates wrote.

The incidence of HF/cardiomyopathy increased with increasing follow-up time for all of the chemotherapy types, but to a greater degree with trastuzumab. The cumulative HF/cardiomyopathy incidence increased from 1.2% at year 1 to 4.3% at year 5 for the anthracycline recipients, which was similar to the increase from 1.3% to 4.5% for those on other chemotherapies. For those with no chemotherapy, the cumulative incidence rose from 0.9% to 3.1%.

In contrast, the cumulative HF/cardiomyopathy incidence among recipients of anthracycline plus trastuzumab was 6.2% after 1 year of follow-up and continued to increase to 20.1% by 5 years.

Compared with no chemotherapy, the risk of incident HF/cardiomyopathy among all women was statistically significantly increased for anthracycline alone (adjusted hazard ratio, 1.40), trastuzumab without anthracycline (HR, 4.12), anthracycline plus trastuzumab (HR, 7.19), and other chemotherapy (HR, 1.49), the investigators said.

The 5-year cumulative incidence for HF/cardiomyopathy associated with each of the chemotherapies was greater in the older age groups, but the hazard ratios for HF/cardiomyopathy associated with chemotherapy use decreased with increasing age. For example, the hazard ratio for HF/cardiomyopathy associated with anthracycline use alone was statistically significant among women younger than 55 years (HR, 2.52) but not among women 55-64 years (HR, 1.61) or older.

According to Ms. Bowles and her associates, this study demonstrates the importance of observational comparative safety and effectiveness studies in providing complementary data to those obtained in clinical trials. "Observational studies allow for estimation of risks and benefits in community practice, which includes patients who may not be eligible for clinical trials. Clinical trials may provide more relevant estimates for patients who are eligible candidates, but many people are not and still receive these treatments in community practice," they wrote.

This work was supported by the National Cancer Institute through an administrative supplement to the Cancer Research Network. Ms. Bowles did not report any financial disclosures, but one of her coauthors, Dr. Larry A. Allen, has received consulting fees from Amgen, Janssen Scientific Affairs, and the Robert Wood Johnson Foundation.

Combination therapy of a tumor necrosis factor inhibitor plus methotrexate inhibited both joint erosion and joint space narrowing independent of disease activity in a 2-year, randomized, controlled trial of 638 patients with early, progressive rheumatoid arthritis.

While joint erosion (JE) has been perceived to be the most critical indicator of permanent disability in RA patients, recent data suggest that joint space narrowing (JSN) may be more important early in the disease process as a predictor of irreversible physical disability (Ann. Rheum. Dis. 2011;70:733-9). "Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients," Dr. Josef S. Smolen of the Medical University of Vienna and Hietzing Hospital, also in Vienna, and his associates wrote online in Annals of the Rheumatic Diseases (2012 [doi 10.1136/annrheumdis-2012-201620]).

The data came from patients enrolled in Abbott’s PREMIER trial, a 2-year, active-controlled, double-blind study of 799 methotrexate-naive patients with early, progressive RA. They were randomly assigned to either combination treatment with subcutaneous adalimumab (ADA; 40 mg every other week) plus oral methotrexate (MTX; titrated to 20 mg/week by week 8, as tolerated), adalimumab monotherapy, or methotrexate monotherapy. Study patients were 18 years of age or older, with RA duration of less than 3 years, 8 or more swollen joints, and 10 or more tender joints.

Of the 799 patients originally randomly assigned in PREMIER, the current analysis included 229 patients in the ADA plus MTX combination group, 205 on ADA monotherapy, and 204 MTX monotherapy patients, all of whom had one or more post-baseline time-averaged disease activity (DAS28) measurements and underwent radiography at baseline and week 52 and/or week 104.

At both the 52 and 104 week time points, the patients receiving combination therapy using ADA and MTX had greater mean reductions from baseline in DAS28 (–3.6 at 52 weeks, –3.8 at 104 weeks) than did those receiving patients receiving ADA monotherapy (–2.8 and –3.1, respectively) or MTX monotherapy (–2.8 and –3.1, respectively). This pattern of treatment responses was evident at week 2 and maintained throughout the 104 weeks of the trial, Dr. Smolen and his associates said.

Approximately half of the patients receiving combination therapy were in the lowest tertile of time–averaged 28-joint disease activity score (TA-DAS28), while patients receiving either adalimumab or methotrexate monotherapy were clustered in the higher TA-DAS28 tertiles. Whereas the radiographic progression of both JE and JSN increased significantly with increasing disease activity in the two monotherapy groups – more so with MTX than ADA – there was far less of a relationship between radiographic progression and disease activity in the combination treatment group, and even less so for JSN than for JE. These findings suggest that ADA plus MTX therapy may have even stronger inhibitory effects on JSN progression than on JE progression despite persistent inflammation, they commented.

While JE scores were not associated with health assessment questionnaire (HAQ-DI) scores at any of the time points examined, JSN scores were positively associated with HAQ-DI scores at both 52 and 104 weeks but not at baseline.

Of 649 patients for whom employment status was known, the presence of JSN was associated with being employed at baseline and at weeks 52 and 104 (P = .02, .007, and .04, respectively) but JE was not. The percentages of employed patients generally decreased with increasing baseline values of JE or JSN, but the relationship was more apparent for JSN (P =.02 vs. P less than .001 for the overall differences among JE and JSN tertiles, respectively). These data indicate that progression of JSN plays a more prominent role than does JE in determining employment status, Dr. Smolen and his associates said.

"Patients with RA frequently lose their jobs early in the course of the disease, with 20%-30% experiencing permanent work disability during the first 2-3 years after diagnosis (Clin. Exp. Rheumatol. 2003;21:S71-4). These data indicate that early control of JSN progression is important not only to protect patients’ physical functioning but [also] to help them maintain the lifestyle they had before RA diagnosis," the investigators said.

"Because of the clinical implications of JSN progression for disability and work impairment, protection from the onset or worsening of JSN should be an important factor when choosing between therapeutic modalities," they concluded.

The study was sponsored by Abbott. Dr. Smolen has financial relationships with Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, MSD (Schering-Plough), Novo-Nordisk, Pfizer (Wyeth), Roche, Sandoz, and UCB. His coauthors have similar disclosures, and four are full-time employees of Abbott.

Combination therapy of a tumor necrosis factor inhibitor plus methotrexate inhibited both joint erosion and joint space narrowing independent of disease activity in a 2-year, randomized, controlled trial of 638 patients with early, progressive rheumatoid arthritis.

While joint erosion (JE) has been perceived to be the most critical indicator of permanent disability in RA patients, recent data suggest that joint space narrowing (JSN) may be more important early in the disease process as a predictor of irreversible physical disability (Ann. Rheum. Dis. 2011;70:733-9). "Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients," Dr. Josef S. Smolen of the Medical University of Vienna and Hietzing Hospital, also in Vienna, and his associates wrote online in Annals of the Rheumatic Diseases (2012 [doi 10.1136/annrheumdis-2012-201620]).

The data came from patients enrolled in Abbott’s PREMIER trial, a 2-year, active-controlled, double-blind study of 799 methotrexate-naive patients with early, progressive RA. They were randomly assigned to either combination treatment with subcutaneous adalimumab (ADA; 40 mg every other week) plus oral methotrexate (MTX; titrated to 20 mg/week by week 8, as tolerated), adalimumab monotherapy, or methotrexate monotherapy. Study patients were 18 years of age or older, with RA duration of less than 3 years, 8 or more swollen joints, and 10 or more tender joints.

Of the 799 patients originally randomly assigned in PREMIER, the current analysis included 229 patients in the ADA plus MTX combination group, 205 on ADA monotherapy, and 204 MTX monotherapy patients, all of whom had one or more post-baseline time-averaged disease activity (DAS28) measurements and underwent radiography at baseline and week 52 and/or week 104.

At both the 52 and 104 week time points, the patients receiving combination therapy using ADA and MTX had greater mean reductions from baseline in DAS28 (–3.6 at 52 weeks, –3.8 at 104 weeks) than did those receiving patients receiving ADA monotherapy (–2.8 and –3.1, respectively) or MTX monotherapy (–2.8 and –3.1, respectively). This pattern of treatment responses was evident at week 2 and maintained throughout the 104 weeks of the trial, Dr. Smolen and his associates said.

Approximately half of the patients receiving combination therapy were in the lowest tertile of time–averaged 28-joint disease activity score (TA-DAS28), while patients receiving either adalimumab or methotrexate monotherapy were clustered in the higher TA-DAS28 tertiles. Whereas the radiographic progression of both JE and JSN increased significantly with increasing disease activity in the two monotherapy groups – more so with MTX than ADA – there was far less of a relationship between radiographic progression and disease activity in the combination treatment group, and even less so for JSN than for JE. These findings suggest that ADA plus MTX therapy may have even stronger inhibitory effects on JSN progression than on JE progression despite persistent inflammation, they commented.

While JE scores were not associated with health assessment questionnaire (HAQ-DI) scores at any of the time points examined, JSN scores were positively associated with HAQ-DI scores at both 52 and 104 weeks but not at baseline.

Of 649 patients for whom employment status was known, the presence of JSN was associated with being employed at baseline and at weeks 52 and 104 (P = .02, .007, and .04, respectively) but JE was not. The percentages of employed patients generally decreased with increasing baseline values of JE or JSN, but the relationship was more apparent for JSN (P =.02 vs. P less than .001 for the overall differences among JE and JSN tertiles, respectively). These data indicate that progression of JSN plays a more prominent role than does JE in determining employment status, Dr. Smolen and his associates said.

"Patients with RA frequently lose their jobs early in the course of the disease, with 20%-30% experiencing permanent work disability during the first 2-3 years after diagnosis (Clin. Exp. Rheumatol. 2003;21:S71-4). These data indicate that early control of JSN progression is important not only to protect patients’ physical functioning but [also] to help them maintain the lifestyle they had before RA diagnosis," the investigators said.

"Because of the clinical implications of JSN progression for disability and work impairment, protection from the onset or worsening of JSN should be an important factor when choosing between therapeutic modalities," they concluded.

The study was sponsored by Abbott. Dr. Smolen has financial relationships with Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, MSD (Schering-Plough), Novo-Nordisk, Pfizer (Wyeth), Roche, Sandoz, and UCB. His coauthors have similar disclosures, and four are full-time employees of Abbott.

Combination therapy of a tumor necrosis factor inhibitor plus methotrexate inhibited both joint erosion and joint space narrowing independent of disease activity in a 2-year, randomized, controlled trial of 638 patients with early, progressive rheumatoid arthritis.

While joint erosion (JE) has been perceived to be the most critical indicator of permanent disability in RA patients, recent data suggest that joint space narrowing (JSN) may be more important early in the disease process as a predictor of irreversible physical disability (Ann. Rheum. Dis. 2011;70:733-9). "Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients," Dr. Josef S. Smolen of the Medical University of Vienna and Hietzing Hospital, also in Vienna, and his associates wrote online in Annals of the Rheumatic Diseases (2012 [doi 10.1136/annrheumdis-2012-201620]).

The data came from patients enrolled in Abbott’s PREMIER trial, a 2-year, active-controlled, double-blind study of 799 methotrexate-naive patients with early, progressive RA. They were randomly assigned to either combination treatment with subcutaneous adalimumab (ADA; 40 mg every other week) plus oral methotrexate (MTX; titrated to 20 mg/week by week 8, as tolerated), adalimumab monotherapy, or methotrexate monotherapy. Study patients were 18 years of age or older, with RA duration of less than 3 years, 8 or more swollen joints, and 10 or more tender joints.

Of the 799 patients originally randomly assigned in PREMIER, the current analysis included 229 patients in the ADA plus MTX combination group, 205 on ADA monotherapy, and 204 MTX monotherapy patients, all of whom had one or more post-baseline time-averaged disease activity (DAS28) measurements and underwent radiography at baseline and week 52 and/or week 104.

At both the 52 and 104 week time points, the patients receiving combination therapy using ADA and MTX had greater mean reductions from baseline in DAS28 (–3.6 at 52 weeks, –3.8 at 104 weeks) than did those receiving patients receiving ADA monotherapy (–2.8 and –3.1, respectively) or MTX monotherapy (–2.8 and –3.1, respectively). This pattern of treatment responses was evident at week 2 and maintained throughout the 104 weeks of the trial, Dr. Smolen and his associates said.

Approximately half of the patients receiving combination therapy were in the lowest tertile of time–averaged 28-joint disease activity score (TA-DAS28), while patients receiving either adalimumab or methotrexate monotherapy were clustered in the higher TA-DAS28 tertiles. Whereas the radiographic progression of both JE and JSN increased significantly with increasing disease activity in the two monotherapy groups – more so with MTX than ADA – there was far less of a relationship between radiographic progression and disease activity in the combination treatment group, and even less so for JSN than for JE. These findings suggest that ADA plus MTX therapy may have even stronger inhibitory effects on JSN progression than on JE progression despite persistent inflammation, they commented.

While JE scores were not associated with health assessment questionnaire (HAQ-DI) scores at any of the time points examined, JSN scores were positively associated with HAQ-DI scores at both 52 and 104 weeks but not at baseline.

Of 649 patients for whom employment status was known, the presence of JSN was associated with being employed at baseline and at weeks 52 and 104 (P = .02, .007, and .04, respectively) but JE was not. The percentages of employed patients generally decreased with increasing baseline values of JE or JSN, but the relationship was more apparent for JSN (P =.02 vs. P less than .001 for the overall differences among JE and JSN tertiles, respectively). These data indicate that progression of JSN plays a more prominent role than does JE in determining employment status, Dr. Smolen and his associates said.

"Patients with RA frequently lose their jobs early in the course of the disease, with 20%-30% experiencing permanent work disability during the first 2-3 years after diagnosis (Clin. Exp. Rheumatol. 2003;21:S71-4). These data indicate that early control of JSN progression is important not only to protect patients’ physical functioning but [also] to help them maintain the lifestyle they had before RA diagnosis," the investigators said.

"Because of the clinical implications of JSN progression for disability and work impairment, protection from the onset or worsening of JSN should be an important factor when choosing between therapeutic modalities," they concluded.

The study was sponsored by Abbott. Dr. Smolen has financial relationships with Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, MSD (Schering-Plough), Novo-Nordisk, Pfizer (Wyeth), Roche, Sandoz, and UCB. His coauthors have similar disclosures, and four are full-time employees of Abbott.