CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Final efficacy results from the phase II OAM4458g trial confirm that the success of MetMAb in previously treated advanced lung cancer lies in accurate biomarker testing.

While some patients gained a striking survival advantage when given the investigational monoclonal antibody as second-or third-line therapy for non–small cell lung cancer (NSCLC), the study group as a whole did not and others actually did worse. The difference appears to be driven by expression of the c-Met receptor.

MetMAb targets hepatocyte growth factor and its receptor, c-Met. Expression of c-Met is associated with a worse prognosis in many cancers, including NSCLC. Met activation by hepatocyte growth factor is also thought to decrease sensitivity to erlotinib (Tarceva). Hence the interest in combining MetMAb with erlotinib. In this trial patients received either a combination of the two drugs or erlotinib with a placebo.

In NSCLC patients whose tumors were classified as Met positive, the addition of MetMAb to erlotinib nearly doubled the median time that they were free of disease from 1.5 months to 2.9 months (hazard ratio, 0.53; log rank P = .04) and tripled median overall survival from 3.8 months to 12.6 months (HR, 0.37; log rank P = .002), Dr. David Spigel said at the annual meeting of the American Society of Clinical Oncology.

When MetMAb plus erlotinib was given to patients with Met-negative tumors, however, median progression-free survival was significantly lower at 1.4 months, compared with 2.7 months in the control arm given erlotinib plus placebo (HR, 1.82; P = .05).

Median overall survival was also shorter with the combination in the Met-negative group – 8.1 months vs. 15.3 months with erlotinib and placebo – although the difference did not reach statistical significance (HR, 1.78; P = .158), said Dr Spigel, director of lung cancer research at the Sarah Cannon Research Institute in Nashville, Tenn.

Invited discussant Dr. Tony Mok, with the Chinese University of Hong Kong, said there’s no doubt that MetMAb should move into phase III evaluation, but stressed the need for accurate biomarker testing in patients to determine Met status.

"This is the key to the success of this drug," he said. "Is this biomarker valid and trustworthy?"

The Met diagnostic test used in the phase II study was developed by Ventana Medical Systems, a tissue diagnostics company owned by Roche, the parent company of the study sponsor, Genentech. Met status was assessed after randomization and prior to unblinding, with 93% of all 137 patients having adequate tissue for evaluation of c-Met by immunohistochemistry. In all, 52% of patients with evaluable tissue were "Met diagnostic positive," defined by at least 50% of tumor cells with moderate or strong staining intensity, Dr. Spigel explained.

Patients were randomized to erlotinib 150 mg daily plus MetMAb 15 mg/kg IV every 3 weeks or the same dosing of erlotinib and placebo. Coprimary end points were progression-free survival in the Met diagnostic–positive and intention-to-treat populations.

In the latter, the combination of MetMAb and erlotinib failed to significantly improve median time to progression over erlotinib (2.2 months vs. 2.6 months; HR, = 1.09; P = .69) or overall survival (8.9 months vs. 7.4 months; HR, 0.80; P = .34), he said.

The researchers performed additional analyses in key subpopulations, suggesting that the benefit from MetMAb is not related to epidermal growth factor receptor mutation or fluorescence in situ hybridization (FISH) status.

Although the patient numbers were small, an overall survival advantage was observed with MetMAb for patients with high Met expression (at least 5 copies) by FISH (HR, 0.60; P = .35), and was maintained in FISH-negative/Met diagnostic–positive patients (HR, 0.37; P = .01), Dr. Spigel said. Patients who were Met diagnostic positive and did not have an epidermal growth factor receptor mutation also gained a survival advantage (HR, 0.42; P = .01).

"Outcomes in the diagnostic subpopulations highlight the importance of developing tools to identify patients who might best benefit from this treatment," he said, adding that immunohistochemistry appears to be more sensitive than FISH in determining benefit from combination MetMAb/erlotinib.

The study confirmed that Met expression by immunohistochemistry is associated with worse outcomes. An analysis of the 68 patients treated with erlotinib plus placebo confirmed that Met expression revealed that progression-free survival was worse among Met diagnostic–positive vs. Met diagnostic–negative patients (1.5 months vs. 2.7 months; HR, 1.71; P = .06), as was overall survival (3.8 months vs. 15.3 months; HR, 2.61; P = .004).

In response to audience questions, Dr. Spigel said it is unknown whether metastatic sites have different Met expression than primary tumor sites or why outcomes are worse in low Met tumors.

Dr. Spigel observed that no new safety concerns emerged in the trial, although patients treated with MetMAb had more peripheral edema that was largely low grade, reversible, and manageable.

A phase III study testing MetMAb plus erlotinib in Met diagnostic–positive patients is expected to start enrolling this year, he said.

Dr. Spigel disclosed a consultant/advisory role with Genentech, which sponsored the study. His coauthors disclosed financial relationships with several firms including employment with Genentech.

CHICAGO – Final efficacy results from the phase II OAM4458g trial confirm that the success of MetMAb in previously treated advanced lung cancer lies in accurate biomarker testing.

While some patients gained a striking survival advantage when given the investigational monoclonal antibody as second-or third-line therapy for non–small cell lung cancer (NSCLC), the study group as a whole did not and others actually did worse. The difference appears to be driven by expression of the c-Met receptor.

MetMAb targets hepatocyte growth factor and its receptor, c-Met. Expression of c-Met is associated with a worse prognosis in many cancers, including NSCLC. Met activation by hepatocyte growth factor is also thought to decrease sensitivity to erlotinib (Tarceva). Hence the interest in combining MetMAb with erlotinib. In this trial patients received either a combination of the two drugs or erlotinib with a placebo.

In NSCLC patients whose tumors were classified as Met positive, the addition of MetMAb to erlotinib nearly doubled the median time that they were free of disease from 1.5 months to 2.9 months (hazard ratio, 0.53; log rank P = .04) and tripled median overall survival from 3.8 months to 12.6 months (HR, 0.37; log rank P = .002), Dr. David Spigel said at the annual meeting of the American Society of Clinical Oncology.

When MetMAb plus erlotinib was given to patients with Met-negative tumors, however, median progression-free survival was significantly lower at 1.4 months, compared with 2.7 months in the control arm given erlotinib plus placebo (HR, 1.82; P = .05).

Median overall survival was also shorter with the combination in the Met-negative group – 8.1 months vs. 15.3 months with erlotinib and placebo – although the difference did not reach statistical significance (HR, 1.78; P = .158), said Dr Spigel, director of lung cancer research at the Sarah Cannon Research Institute in Nashville, Tenn.

Invited discussant Dr. Tony Mok, with the Chinese University of Hong Kong, said there’s no doubt that MetMAb should move into phase III evaluation, but stressed the need for accurate biomarker testing in patients to determine Met status.

"This is the key to the success of this drug," he said. "Is this biomarker valid and trustworthy?"

The Met diagnostic test used in the phase II study was developed by Ventana Medical Systems, a tissue diagnostics company owned by Roche, the parent company of the study sponsor, Genentech. Met status was assessed after randomization and prior to unblinding, with 93% of all 137 patients having adequate tissue for evaluation of c-Met by immunohistochemistry. In all, 52% of patients with evaluable tissue were "Met diagnostic positive," defined by at least 50% of tumor cells with moderate or strong staining intensity, Dr. Spigel explained.

Patients were randomized to erlotinib 150 mg daily plus MetMAb 15 mg/kg IV every 3 weeks or the same dosing of erlotinib and placebo. Coprimary end points were progression-free survival in the Met diagnostic–positive and intention-to-treat populations.

In the latter, the combination of MetMAb and erlotinib failed to significantly improve median time to progression over erlotinib (2.2 months vs. 2.6 months; HR, = 1.09; P = .69) or overall survival (8.9 months vs. 7.4 months; HR, 0.80; P = .34), he said.

The researchers performed additional analyses in key subpopulations, suggesting that the benefit from MetMAb is not related to epidermal growth factor receptor mutation or fluorescence in situ hybridization (FISH) status.

Although the patient numbers were small, an overall survival advantage was observed with MetMAb for patients with high Met expression (at least 5 copies) by FISH (HR, 0.60; P = .35), and was maintained in FISH-negative/Met diagnostic–positive patients (HR, 0.37; P = .01), Dr. Spigel said. Patients who were Met diagnostic positive and did not have an epidermal growth factor receptor mutation also gained a survival advantage (HR, 0.42; P = .01).

"Outcomes in the diagnostic subpopulations highlight the importance of developing tools to identify patients who might best benefit from this treatment," he said, adding that immunohistochemistry appears to be more sensitive than FISH in determining benefit from combination MetMAb/erlotinib.

The study confirmed that Met expression by immunohistochemistry is associated with worse outcomes. An analysis of the 68 patients treated with erlotinib plus placebo confirmed that Met expression revealed that progression-free survival was worse among Met diagnostic–positive vs. Met diagnostic–negative patients (1.5 months vs. 2.7 months; HR, 1.71; P = .06), as was overall survival (3.8 months vs. 15.3 months; HR, 2.61; P = .004).

In response to audience questions, Dr. Spigel said it is unknown whether metastatic sites have different Met expression than primary tumor sites or why outcomes are worse in low Met tumors.

Dr. Spigel observed that no new safety concerns emerged in the trial, although patients treated with MetMAb had more peripheral edema that was largely low grade, reversible, and manageable.

A phase III study testing MetMAb plus erlotinib in Met diagnostic–positive patients is expected to start enrolling this year, he said.

Dr. Spigel disclosed a consultant/advisory role with Genentech, which sponsored the study. His coauthors disclosed financial relationships with several firms including employment with Genentech.

CHICAGO – Final efficacy results from the phase II OAM4458g trial confirm that the success of MetMAb in previously treated advanced lung cancer lies in accurate biomarker testing.

While some patients gained a striking survival advantage when given the investigational monoclonal antibody as second-or third-line therapy for non–small cell lung cancer (NSCLC), the study group as a whole did not and others actually did worse. The difference appears to be driven by expression of the c-Met receptor.

MetMAb targets hepatocyte growth factor and its receptor, c-Met. Expression of c-Met is associated with a worse prognosis in many cancers, including NSCLC. Met activation by hepatocyte growth factor is also thought to decrease sensitivity to erlotinib (Tarceva). Hence the interest in combining MetMAb with erlotinib. In this trial patients received either a combination of the two drugs or erlotinib with a placebo.

In NSCLC patients whose tumors were classified as Met positive, the addition of MetMAb to erlotinib nearly doubled the median time that they were free of disease from 1.5 months to 2.9 months (hazard ratio, 0.53; log rank P = .04) and tripled median overall survival from 3.8 months to 12.6 months (HR, 0.37; log rank P = .002), Dr. David Spigel said at the annual meeting of the American Society of Clinical Oncology.

When MetMAb plus erlotinib was given to patients with Met-negative tumors, however, median progression-free survival was significantly lower at 1.4 months, compared with 2.7 months in the control arm given erlotinib plus placebo (HR, 1.82; P = .05).

Median overall survival was also shorter with the combination in the Met-negative group – 8.1 months vs. 15.3 months with erlotinib and placebo – although the difference did not reach statistical significance (HR, 1.78; P = .158), said Dr Spigel, director of lung cancer research at the Sarah Cannon Research Institute in Nashville, Tenn.

Invited discussant Dr. Tony Mok, with the Chinese University of Hong Kong, said there’s no doubt that MetMAb should move into phase III evaluation, but stressed the need for accurate biomarker testing in patients to determine Met status.

"This is the key to the success of this drug," he said. "Is this biomarker valid and trustworthy?"

The Met diagnostic test used in the phase II study was developed by Ventana Medical Systems, a tissue diagnostics company owned by Roche, the parent company of the study sponsor, Genentech. Met status was assessed after randomization and prior to unblinding, with 93% of all 137 patients having adequate tissue for evaluation of c-Met by immunohistochemistry. In all, 52% of patients with evaluable tissue were "Met diagnostic positive," defined by at least 50% of tumor cells with moderate or strong staining intensity, Dr. Spigel explained.

Patients were randomized to erlotinib 150 mg daily plus MetMAb 15 mg/kg IV every 3 weeks or the same dosing of erlotinib and placebo. Coprimary end points were progression-free survival in the Met diagnostic–positive and intention-to-treat populations.

In the latter, the combination of MetMAb and erlotinib failed to significantly improve median time to progression over erlotinib (2.2 months vs. 2.6 months; HR, = 1.09; P = .69) or overall survival (8.9 months vs. 7.4 months; HR, 0.80; P = .34), he said.

The researchers performed additional analyses in key subpopulations, suggesting that the benefit from MetMAb is not related to epidermal growth factor receptor mutation or fluorescence in situ hybridization (FISH) status.

Although the patient numbers were small, an overall survival advantage was observed with MetMAb for patients with high Met expression (at least 5 copies) by FISH (HR, 0.60; P = .35), and was maintained in FISH-negative/Met diagnostic–positive patients (HR, 0.37; P = .01), Dr. Spigel said. Patients who were Met diagnostic positive and did not have an epidermal growth factor receptor mutation also gained a survival advantage (HR, 0.42; P = .01).

"Outcomes in the diagnostic subpopulations highlight the importance of developing tools to identify patients who might best benefit from this treatment," he said, adding that immunohistochemistry appears to be more sensitive than FISH in determining benefit from combination MetMAb/erlotinib.

The study confirmed that Met expression by immunohistochemistry is associated with worse outcomes. An analysis of the 68 patients treated with erlotinib plus placebo confirmed that Met expression revealed that progression-free survival was worse among Met diagnostic–positive vs. Met diagnostic–negative patients (1.5 months vs. 2.7 months; HR, 1.71; P = .06), as was overall survival (3.8 months vs. 15.3 months; HR, 2.61; P = .004).

In response to audience questions, Dr. Spigel said it is unknown whether metastatic sites have different Met expression than primary tumor sites or why outcomes are worse in low Met tumors.

Dr. Spigel observed that no new safety concerns emerged in the trial, although patients treated with MetMAb had more peripheral edema that was largely low grade, reversible, and manageable.

A phase III study testing MetMAb plus erlotinib in Met diagnostic–positive patients is expected to start enrolling this year, he said.

Dr. Spigel disclosed a consultant/advisory role with Genentech, which sponsored the study. His coauthors disclosed financial relationships with several firms including employment with Genentech.

Statin therapy appears to reduce the risk of recurrent stroke among patients with diabetes or the metabolic syndrome to the same degree that it does in patients who have neither disorder, according to a planned post hoc analysis of data collected in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial.

However, since patients with diabetes start off with a much higher risk of recurrent stroke, their risk remains higher than that of nondiabetic patients even after statin therapy, Dr. Alfred Callahan of Vanderbilt University, Nashville, Tenn., and his associates reported online June 13 in Archives of Neurology.

Until now, no information has been available on the effect of statin treatment on secondary stroke prevention in patients with type 2 diabetes or the metabolic syndrome, the investigators noted.

The primary conclusion of the SPARCL clinical trial was that atorvastatin (Lipitor) reduced stroke risk in general. For this secondary analysis, Dr. Callahan and his colleagues assessed stroke risk in 794 adults who had type 2 diabetes, 642 who had the metabolic syndrome, and a reference group of 3,295 who had neither disorder.

The study subjects were ambulatory men and women with no known coronary heart disease who had had ischemic stroke, hemorrhagic stroke, or transient ischemic attack (TIA) 1-6 months before undergoing randomization in the SPARCL trial. They were treated at 205 medical centers in Africa, Australia, Europe, the Middle East, North America, and South America. The mean age was 63 years, and subjects were assessed every 6 months for a mean of 5 years.

Treatment with atorvastatin decreased LDL cholesterol levels to a similar degree across the three study groups, and lowered triglycerides by 11% in the group with diabetes, 20% in the group with metabolic syndrome, and 9% in the reference group.

Despite these treatment benefits, subjects with diabetes remained at increased risk of recurrent stroke (hazard ratio, 1.62), of major cardiovascular events (HR, 1.66), and of revascularization procedures (HR, 2.39), compared with the reference group. Subjects with metabolic syndrome were at increased risk of revascularization procedures (HR, 1.78) but not of other adverse cardiovascular outcomes.

At the conclusion of the study, the rate of recurrent stroke was 18% in patients with diabetes, 11% in those with metabolic syndrome, and 11% in the reference group.

"There was no evidence of a difference in treatment effect" among the three study groups, Dr. Callahan and his associates said (Arch. Neurol. 2011 June 13 [doi:10.1001/archneurol.2011.146]).

"These results should be viewed as exploratory" because the SPARCL trial was not powered to test for subgroup effects, they noted.

However, the findings agree with those of the Cholesterol Treatment Trialists’ collaboration, which also found that the effect of statins on stroke risk was similar between diabetic and nondiabetic patients, the researchers added.

Pfizer sponsored the study. Dr. Callahan reported receiving support from Pfizer, Sanofi-Aventis, and Bristol-Myers Squibb. His associates reported ties to numerous pharmaceutical and device companies.

Statin therapy appears to reduce the risk of recurrent stroke among patients with diabetes or the metabolic syndrome to the same degree that it does in patients who have neither disorder, according to a planned post hoc analysis of data collected in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial.

However, since patients with diabetes start off with a much higher risk of recurrent stroke, their risk remains higher than that of nondiabetic patients even after statin therapy, Dr. Alfred Callahan of Vanderbilt University, Nashville, Tenn., and his associates reported online June 13 in Archives of Neurology.

Until now, no information has been available on the effect of statin treatment on secondary stroke prevention in patients with type 2 diabetes or the metabolic syndrome, the investigators noted.

The primary conclusion of the SPARCL clinical trial was that atorvastatin (Lipitor) reduced stroke risk in general. For this secondary analysis, Dr. Callahan and his colleagues assessed stroke risk in 794 adults who had type 2 diabetes, 642 who had the metabolic syndrome, and a reference group of 3,295 who had neither disorder.

The study subjects were ambulatory men and women with no known coronary heart disease who had had ischemic stroke, hemorrhagic stroke, or transient ischemic attack (TIA) 1-6 months before undergoing randomization in the SPARCL trial. They were treated at 205 medical centers in Africa, Australia, Europe, the Middle East, North America, and South America. The mean age was 63 years, and subjects were assessed every 6 months for a mean of 5 years.

Treatment with atorvastatin decreased LDL cholesterol levels to a similar degree across the three study groups, and lowered triglycerides by 11% in the group with diabetes, 20% in the group with metabolic syndrome, and 9% in the reference group.

Despite these treatment benefits, subjects with diabetes remained at increased risk of recurrent stroke (hazard ratio, 1.62), of major cardiovascular events (HR, 1.66), and of revascularization procedures (HR, 2.39), compared with the reference group. Subjects with metabolic syndrome were at increased risk of revascularization procedures (HR, 1.78) but not of other adverse cardiovascular outcomes.

At the conclusion of the study, the rate of recurrent stroke was 18% in patients with diabetes, 11% in those with metabolic syndrome, and 11% in the reference group.

"There was no evidence of a difference in treatment effect" among the three study groups, Dr. Callahan and his associates said (Arch. Neurol. 2011 June 13 [doi:10.1001/archneurol.2011.146]).

"These results should be viewed as exploratory" because the SPARCL trial was not powered to test for subgroup effects, they noted.

However, the findings agree with those of the Cholesterol Treatment Trialists’ collaboration, which also found that the effect of statins on stroke risk was similar between diabetic and nondiabetic patients, the researchers added.

Pfizer sponsored the study. Dr. Callahan reported receiving support from Pfizer, Sanofi-Aventis, and Bristol-Myers Squibb. His associates reported ties to numerous pharmaceutical and device companies.

Statin therapy appears to reduce the risk of recurrent stroke among patients with diabetes or the metabolic syndrome to the same degree that it does in patients who have neither disorder, according to a planned post hoc analysis of data collected in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels clinical trial.

However, since patients with diabetes start off with a much higher risk of recurrent stroke, their risk remains higher than that of nondiabetic patients even after statin therapy, Dr. Alfred Callahan of Vanderbilt University, Nashville, Tenn., and his associates reported online June 13 in Archives of Neurology.

Until now, no information has been available on the effect of statin treatment on secondary stroke prevention in patients with type 2 diabetes or the metabolic syndrome, the investigators noted.

The primary conclusion of the SPARCL clinical trial was that atorvastatin (Lipitor) reduced stroke risk in general. For this secondary analysis, Dr. Callahan and his colleagues assessed stroke risk in 794 adults who had type 2 diabetes, 642 who had the metabolic syndrome, and a reference group of 3,295 who had neither disorder.

The study subjects were ambulatory men and women with no known coronary heart disease who had had ischemic stroke, hemorrhagic stroke, or transient ischemic attack (TIA) 1-6 months before undergoing randomization in the SPARCL trial. They were treated at 205 medical centers in Africa, Australia, Europe, the Middle East, North America, and South America. The mean age was 63 years, and subjects were assessed every 6 months for a mean of 5 years.

Treatment with atorvastatin decreased LDL cholesterol levels to a similar degree across the three study groups, and lowered triglycerides by 11% in the group with diabetes, 20% in the group with metabolic syndrome, and 9% in the reference group.

Despite these treatment benefits, subjects with diabetes remained at increased risk of recurrent stroke (hazard ratio, 1.62), of major cardiovascular events (HR, 1.66), and of revascularization procedures (HR, 2.39), compared with the reference group. Subjects with metabolic syndrome were at increased risk of revascularization procedures (HR, 1.78) but not of other adverse cardiovascular outcomes.

At the conclusion of the study, the rate of recurrent stroke was 18% in patients with diabetes, 11% in those with metabolic syndrome, and 11% in the reference group.

"There was no evidence of a difference in treatment effect" among the three study groups, Dr. Callahan and his associates said (Arch. Neurol. 2011 June 13 [doi:10.1001/archneurol.2011.146]).

"These results should be viewed as exploratory" because the SPARCL trial was not powered to test for subgroup effects, they noted.

However, the findings agree with those of the Cholesterol Treatment Trialists’ collaboration, which also found that the effect of statins on stroke risk was similar between diabetic and nondiabetic patients, the researchers added.

Pfizer sponsored the study. Dr. Callahan reported receiving support from Pfizer, Sanofi-Aventis, and Bristol-Myers Squibb. His associates reported ties to numerous pharmaceutical and device companies.

Splenomegaly

CHICAGO—Two phase 3 studies demonstrate the effectiveness of the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in treating patients with myelofibrosis (MF), according to presentations at the 2011 ASCO Annual Meeting.

Ruxolitinib has the potential to change the treatment landscape in MF, said Alessandro Vannucchi, MD, of the University of Florence, who reported the results of the COMFORT-II trial.

Srdan Verostovsek, MD, PhD, of the MD Anderson Cancer Center, presented results from COMFORT-I.

COMFORT-II

In the COMFORT-II trial, ruxolitinib produced a volumetric spleen size reduction of 35% or greater in 28.5% of MF patients at 48 weeks. None of the patients receiving best available therapy (BAT) experienced such a reduction, Dr Vannucchi said.

At week 24, 31.9% of ruxolitinib-treated patients had a 35% or greater volumetric spleen size reduction, compared to none of the BAT-treated patients. Ruxolitinib also showed a marked improvement in overall quality of life measures, functioning, and symptoms relative to the BAT arm.

This open-label, phase 3 study included 146 patients randomized to ruxolitinib starting at doses of 15 or 20 mg twice daily and 73 patients randomized to BAT, which was administered at doses and schedules determined by the investigator.

Two-thirds of the BAT patients received at least one medication, and one-third received no medication. The most commonly administered agents were hydroxyurea (47% of patients) and glucocorticoids (16% of patients).

All study participants had intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The safety profile of ruxolitinib was consistent with previous studies, Dr Vannucchi said. The most common grade 3 or higher adverse events in the ruxolitinib arm were anemia and thrombocytopenia. In the BAT arm, the most common events were anemia, thrombocytopenia, pneumonia, and dyspnea.

COMFORT-I

The COMFORT-I trial enrolled 309 patients with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. They were randomly assigned to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients).

Ruxolitinib was dosed at 15 mg or 20 mg, depending on the baseline platelet count. Patients in the placebo arm could cross over to the ruxolitinib arm upon disease progression, and nearly a quarter of patients did cross over (11% prior to week 24 and 13% after week 24).

The median follow-up was 32 weeks. A significantly higher proportion of patients on the ruxolitinib arm (41.9%) attained the primary endpoint of at least a 35% reduction in spleen volume after 24 weeks of therapy compared with placebo patients (0.7%), Dr Verstovsek reported.

Ruxolitinib was also more effective than placebo for improving symptom burden, as 45.9% of patients in the ruxolitinib had at least a 50% improvement in symptom burden, compared to 5.3% of placebo-treated patients.

Symptoms that significantly improved with ruxolitinib included abdominal discomfort, pain under the left ribs, early satiety, night sweats, itching, bone or muscle pain, and inactivity.

“Data from the COMFORT studies indicate that ruxolitinib has the potential to significantly improve the current treatment landscape for most patients with MF,” Dr Vannucchi said.

Splenomegaly

CHICAGO—Two phase 3 studies demonstrate the effectiveness of the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in treating patients with myelofibrosis (MF), according to presentations at the 2011 ASCO Annual Meeting.

Ruxolitinib has the potential to change the treatment landscape in MF, said Alessandro Vannucchi, MD, of the University of Florence, who reported the results of the COMFORT-II trial.

Srdan Verostovsek, MD, PhD, of the MD Anderson Cancer Center, presented results from COMFORT-I.

COMFORT-II

In the COMFORT-II trial, ruxolitinib produced a volumetric spleen size reduction of 35% or greater in 28.5% of MF patients at 48 weeks. None of the patients receiving best available therapy (BAT) experienced such a reduction, Dr Vannucchi said.

At week 24, 31.9% of ruxolitinib-treated patients had a 35% or greater volumetric spleen size reduction, compared to none of the BAT-treated patients. Ruxolitinib also showed a marked improvement in overall quality of life measures, functioning, and symptoms relative to the BAT arm.

This open-label, phase 3 study included 146 patients randomized to ruxolitinib starting at doses of 15 or 20 mg twice daily and 73 patients randomized to BAT, which was administered at doses and schedules determined by the investigator.

Two-thirds of the BAT patients received at least one medication, and one-third received no medication. The most commonly administered agents were hydroxyurea (47% of patients) and glucocorticoids (16% of patients).

All study participants had intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The safety profile of ruxolitinib was consistent with previous studies, Dr Vannucchi said. The most common grade 3 or higher adverse events in the ruxolitinib arm were anemia and thrombocytopenia. In the BAT arm, the most common events were anemia, thrombocytopenia, pneumonia, and dyspnea.

COMFORT-I

The COMFORT-I trial enrolled 309 patients with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. They were randomly assigned to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients).

Ruxolitinib was dosed at 15 mg or 20 mg, depending on the baseline platelet count. Patients in the placebo arm could cross over to the ruxolitinib arm upon disease progression, and nearly a quarter of patients did cross over (11% prior to week 24 and 13% after week 24).

The median follow-up was 32 weeks. A significantly higher proportion of patients on the ruxolitinib arm (41.9%) attained the primary endpoint of at least a 35% reduction in spleen volume after 24 weeks of therapy compared with placebo patients (0.7%), Dr Verstovsek reported.

Ruxolitinib was also more effective than placebo for improving symptom burden, as 45.9% of patients in the ruxolitinib had at least a 50% improvement in symptom burden, compared to 5.3% of placebo-treated patients.

Symptoms that significantly improved with ruxolitinib included abdominal discomfort, pain under the left ribs, early satiety, night sweats, itching, bone or muscle pain, and inactivity.

“Data from the COMFORT studies indicate that ruxolitinib has the potential to significantly improve the current treatment landscape for most patients with MF,” Dr Vannucchi said.

Splenomegaly

CHICAGO—Two phase 3 studies demonstrate the effectiveness of the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in treating patients with myelofibrosis (MF), according to presentations at the 2011 ASCO Annual Meeting.

Ruxolitinib has the potential to change the treatment landscape in MF, said Alessandro Vannucchi, MD, of the University of Florence, who reported the results of the COMFORT-II trial.

Srdan Verostovsek, MD, PhD, of the MD Anderson Cancer Center, presented results from COMFORT-I.

COMFORT-II

In the COMFORT-II trial, ruxolitinib produced a volumetric spleen size reduction of 35% or greater in 28.5% of MF patients at 48 weeks. None of the patients receiving best available therapy (BAT) experienced such a reduction, Dr Vannucchi said.

At week 24, 31.9% of ruxolitinib-treated patients had a 35% or greater volumetric spleen size reduction, compared to none of the BAT-treated patients. Ruxolitinib also showed a marked improvement in overall quality of life measures, functioning, and symptoms relative to the BAT arm.

This open-label, phase 3 study included 146 patients randomized to ruxolitinib starting at doses of 15 or 20 mg twice daily and 73 patients randomized to BAT, which was administered at doses and schedules determined by the investigator.

Two-thirds of the BAT patients received at least one medication, and one-third received no medication. The most commonly administered agents were hydroxyurea (47% of patients) and glucocorticoids (16% of patients).

All study participants had intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.

The safety profile of ruxolitinib was consistent with previous studies, Dr Vannucchi said. The most common grade 3 or higher adverse events in the ruxolitinib arm were anemia and thrombocytopenia. In the BAT arm, the most common events were anemia, thrombocytopenia, pneumonia, and dyspnea.

COMFORT-I

The COMFORT-I trial enrolled 309 patients with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. They were randomly assigned to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients).

Ruxolitinib was dosed at 15 mg or 20 mg, depending on the baseline platelet count. Patients in the placebo arm could cross over to the ruxolitinib arm upon disease progression, and nearly a quarter of patients did cross over (11% prior to week 24 and 13% after week 24).

The median follow-up was 32 weeks. A significantly higher proportion of patients on the ruxolitinib arm (41.9%) attained the primary endpoint of at least a 35% reduction in spleen volume after 24 weeks of therapy compared with placebo patients (0.7%), Dr Verstovsek reported.

Ruxolitinib was also more effective than placebo for improving symptom burden, as 45.9% of patients in the ruxolitinib had at least a 50% improvement in symptom burden, compared to 5.3% of placebo-treated patients.

Symptoms that significantly improved with ruxolitinib included abdominal discomfort, pain under the left ribs, early satiety, night sweats, itching, bone or muscle pain, and inactivity.

“Data from the COMFORT studies indicate that ruxolitinib has the potential to significantly improve the current treatment landscape for most patients with MF,” Dr Vannucchi said.