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The liver drives RBC elimination, iron recycling
“The liver, not the spleen, is the major on-demand site of red blood cell elimination and iron recycling,” according to Filip Swirski, PhD, of the Massachusetts General Hospital Center for Systems Biology, and his colleagues.
The liver relies on a buffer system consisting of bone marrow–derived monocytes that consume damaged red blood cells (RBCs) in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling, the researchers concluded in a study published in Nature Medicine.
The study was designed to examine how the body clears old and damaged RBCs without releasing toxic levels of free iron. Damaged RBCs can release unbound forms of iron-carrying hemoglobin, which can cause kidney injury and can lead to anemia.
The researchers used several different models of RBC damage to examine RBC clearance and iron recycling in a mouse model. Damaged RBCs in the bloodstream prompted an increase in monocytes that took up the damaged cells and traveled to both the liver and the spleen. Within hours, almost all of the damaged RBCs were located within specialized macrophages seen only in the liver. Chemokines drew the monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1–expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+Tim-4neg macrophages are transient, reside alongside embryonically derived T-cell immunoglobulin and mucin domain containing 4high Kupffer cells, and depend on the growth factor Csf1 and the transcription factor Nrf2, the researchers wrote.
Blocking that process resulted in impaired RBC clearance, toxic levels of free iron and hemoglobin, and signs of liver and kidney damage.
“If overactive, (the mechanism) could remove too many RBCs, but if (the mechanism is) sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions,” Dr. Swirski said in a press release.
The researchers had no financial conflicts of interest. The study was funded by the National Institutes of Health.
On Twitter @maryjodales
“The liver, not the spleen, is the major on-demand site of red blood cell elimination and iron recycling,” according to Filip Swirski, PhD, of the Massachusetts General Hospital Center for Systems Biology, and his colleagues.
The liver relies on a buffer system consisting of bone marrow–derived monocytes that consume damaged red blood cells (RBCs) in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling, the researchers concluded in a study published in Nature Medicine.
The study was designed to examine how the body clears old and damaged RBCs without releasing toxic levels of free iron. Damaged RBCs can release unbound forms of iron-carrying hemoglobin, which can cause kidney injury and can lead to anemia.
The researchers used several different models of RBC damage to examine RBC clearance and iron recycling in a mouse model. Damaged RBCs in the bloodstream prompted an increase in monocytes that took up the damaged cells and traveled to both the liver and the spleen. Within hours, almost all of the damaged RBCs were located within specialized macrophages seen only in the liver. Chemokines drew the monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1–expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+Tim-4neg macrophages are transient, reside alongside embryonically derived T-cell immunoglobulin and mucin domain containing 4high Kupffer cells, and depend on the growth factor Csf1 and the transcription factor Nrf2, the researchers wrote.
Blocking that process resulted in impaired RBC clearance, toxic levels of free iron and hemoglobin, and signs of liver and kidney damage.
“If overactive, (the mechanism) could remove too many RBCs, but if (the mechanism is) sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions,” Dr. Swirski said in a press release.
The researchers had no financial conflicts of interest. The study was funded by the National Institutes of Health.
On Twitter @maryjodales
“The liver, not the spleen, is the major on-demand site of red blood cell elimination and iron recycling,” according to Filip Swirski, PhD, of the Massachusetts General Hospital Center for Systems Biology, and his colleagues.
The liver relies on a buffer system consisting of bone marrow–derived monocytes that consume damaged red blood cells (RBCs) in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling, the researchers concluded in a study published in Nature Medicine.
The study was designed to examine how the body clears old and damaged RBCs without releasing toxic levels of free iron. Damaged RBCs can release unbound forms of iron-carrying hemoglobin, which can cause kidney injury and can lead to anemia.
The researchers used several different models of RBC damage to examine RBC clearance and iron recycling in a mouse model. Damaged RBCs in the bloodstream prompted an increase in monocytes that took up the damaged cells and traveled to both the liver and the spleen. Within hours, almost all of the damaged RBCs were located within specialized macrophages seen only in the liver. Chemokines drew the monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1–expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN1+Tim-4neg macrophages are transient, reside alongside embryonically derived T-cell immunoglobulin and mucin domain containing 4high Kupffer cells, and depend on the growth factor Csf1 and the transcription factor Nrf2, the researchers wrote.
Blocking that process resulted in impaired RBC clearance, toxic levels of free iron and hemoglobin, and signs of liver and kidney damage.
“If overactive, (the mechanism) could remove too many RBCs, but if (the mechanism is) sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions,” Dr. Swirski said in a press release.
The researchers had no financial conflicts of interest. The study was funded by the National Institutes of Health.
On Twitter @maryjodales
FROM NATURE MEDICINE
New Digital Editor Appointed for Cutis®
We are pleased to announce that Gary Goldenberg, MD, has been named Digital Editor of Cutis. In this new role, Dr. Goldenberg will work closely with our Editorial Board and editorial/publishing staff on our website, www.cutis.com. Dr. Goldenberg is Assistant Clinical Professor of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, and Medical Director of the Dermatology Faculty Practice at The Mount Sinai Medical Center, New York. Dr. Goldenberg has been a member of the Cutis Editorial Board since April 2008 due to his expertise in dermatopathology as well as medical and cosmetic dermatology. Over the years, Dr. Goldenberg’s involvement in the journal’s presence in print and online has expanded to include a regular series of Cosmetic Dermatology articles and video commentaries on practice management topics. With Dr. Goldenberg’s oversight, we will expand our offerings of highly practical content in the digital arena with an emphasis on resources for the practicing dermatologist.
“We welcome Gary as our first Digital Editor of Cutis and thank him for agreeing to lead us into the future,” said Cutis Editor-in-Chief Vincent A. DeLeo, MD. “Cutis has been a leader in print readership among dermatologists and with Gary’s input, we will be able to offer more to our readers online.”
We are pleased to announce that Gary Goldenberg, MD, has been named Digital Editor of Cutis. In this new role, Dr. Goldenberg will work closely with our Editorial Board and editorial/publishing staff on our website, www.cutis.com. Dr. Goldenberg is Assistant Clinical Professor of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, and Medical Director of the Dermatology Faculty Practice at The Mount Sinai Medical Center, New York. Dr. Goldenberg has been a member of the Cutis Editorial Board since April 2008 due to his expertise in dermatopathology as well as medical and cosmetic dermatology. Over the years, Dr. Goldenberg’s involvement in the journal’s presence in print and online has expanded to include a regular series of Cosmetic Dermatology articles and video commentaries on practice management topics. With Dr. Goldenberg’s oversight, we will expand our offerings of highly practical content in the digital arena with an emphasis on resources for the practicing dermatologist.
“We welcome Gary as our first Digital Editor of Cutis and thank him for agreeing to lead us into the future,” said Cutis Editor-in-Chief Vincent A. DeLeo, MD. “Cutis has been a leader in print readership among dermatologists and with Gary’s input, we will be able to offer more to our readers online.”
We are pleased to announce that Gary Goldenberg, MD, has been named Digital Editor of Cutis. In this new role, Dr. Goldenberg will work closely with our Editorial Board and editorial/publishing staff on our website, www.cutis.com. Dr. Goldenberg is Assistant Clinical Professor of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, and Medical Director of the Dermatology Faculty Practice at The Mount Sinai Medical Center, New York. Dr. Goldenberg has been a member of the Cutis Editorial Board since April 2008 due to his expertise in dermatopathology as well as medical and cosmetic dermatology. Over the years, Dr. Goldenberg’s involvement in the journal’s presence in print and online has expanded to include a regular series of Cosmetic Dermatology articles and video commentaries on practice management topics. With Dr. Goldenberg’s oversight, we will expand our offerings of highly practical content in the digital arena with an emphasis on resources for the practicing dermatologist.
“We welcome Gary as our first Digital Editor of Cutis and thank him for agreeing to lead us into the future,” said Cutis Editor-in-Chief Vincent A. DeLeo, MD. “Cutis has been a leader in print readership among dermatologists and with Gary’s input, we will be able to offer more to our readers online.”
Study challenges previous notions about RBC disposal
A new study contradicts previous beliefs about how the body disposes of red blood cells (RBCs) and recycles their iron.
The work suggests the accumulation and removal of aged or damaged RBCs largely takes place in the liver rather than the spleen, and the same is true for iron
recycling.
Researchers believe this discovery, published in Nature Medicine, could lead to improved treatment or prevention of anemia or iron toxicity.
“Textbooks tell us that red blood cells are eliminated in the spleen by specialized macrophages that live in that organ, but our study shows that the liver—not the spleen—is the major on-demand site of red blood cell elimination and iron recycling,” said study author Filip Swirski, PhD, of Massachusetts General Hospital in Boston.
“In addition to identifying the liver as the primary site of these processes, we also identified a transient population of bone-marrow-derived immune cells as the recycling cells.”
Dr Swirski and his colleagues used several different models of RBC damage to investigate the mechanisms involved in RBC clearance and the recycling of their iron.
Experiments in mice revealed that the presence of damaged RBCs in the bloodstream led to a rapid increase in a specific population of monocytes. These cells took up the damaged RBCs and traveled to both the liver and the spleen.
Several hours later, almost all of those RBCs were located within a population of specialized macrophages that were observed only in the liver. Those macrophages eventually disappeared once they were no longer needed.
The researchers also showed that expression of chemokines draws RBC-ingesting monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Blocking that process led to several indicators of impaired RBC clearance, including toxic levels of free iron and hemoglobin and signs of liver and kidney damage.
“The fact that the liver is the main organ of RBC removal and iron recycling is surprising, as is the fact that the liver relies on a buffer system consisting of bone marrow-derived monocytes that consume damaged red blood cells in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling,” Dr Swirski said.
“The mechanism we identified could be either helpful or damaging, depending on the conditions. If overactive, it could remove too many RBCs, but if it’s sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions.” 
A new study contradicts previous beliefs about how the body disposes of red blood cells (RBCs) and recycles their iron.
The work suggests the accumulation and removal of aged or damaged RBCs largely takes place in the liver rather than the spleen, and the same is true for iron
recycling.
Researchers believe this discovery, published in Nature Medicine, could lead to improved treatment or prevention of anemia or iron toxicity.
“Textbooks tell us that red blood cells are eliminated in the spleen by specialized macrophages that live in that organ, but our study shows that the liver—not the spleen—is the major on-demand site of red blood cell elimination and iron recycling,” said study author Filip Swirski, PhD, of Massachusetts General Hospital in Boston.
“In addition to identifying the liver as the primary site of these processes, we also identified a transient population of bone-marrow-derived immune cells as the recycling cells.”
Dr Swirski and his colleagues used several different models of RBC damage to investigate the mechanisms involved in RBC clearance and the recycling of their iron.
Experiments in mice revealed that the presence of damaged RBCs in the bloodstream led to a rapid increase in a specific population of monocytes. These cells took up the damaged RBCs and traveled to both the liver and the spleen.
Several hours later, almost all of those RBCs were located within a population of specialized macrophages that were observed only in the liver. Those macrophages eventually disappeared once they were no longer needed.
The researchers also showed that expression of chemokines draws RBC-ingesting monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Blocking that process led to several indicators of impaired RBC clearance, including toxic levels of free iron and hemoglobin and signs of liver and kidney damage.
“The fact that the liver is the main organ of RBC removal and iron recycling is surprising, as is the fact that the liver relies on a buffer system consisting of bone marrow-derived monocytes that consume damaged red blood cells in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling,” Dr Swirski said.
“The mechanism we identified could be either helpful or damaging, depending on the conditions. If overactive, it could remove too many RBCs, but if it’s sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions.”
A new study contradicts previous beliefs about how the body disposes of red blood cells (RBCs) and recycles their iron.
The work suggests the accumulation and removal of aged or damaged RBCs largely takes place in the liver rather than the spleen, and the same is true for iron
recycling.
Researchers believe this discovery, published in Nature Medicine, could lead to improved treatment or prevention of anemia or iron toxicity.
“Textbooks tell us that red blood cells are eliminated in the spleen by specialized macrophages that live in that organ, but our study shows that the liver—not the spleen—is the major on-demand site of red blood cell elimination and iron recycling,” said study author Filip Swirski, PhD, of Massachusetts General Hospital in Boston.
“In addition to identifying the liver as the primary site of these processes, we also identified a transient population of bone-marrow-derived immune cells as the recycling cells.”
Dr Swirski and his colleagues used several different models of RBC damage to investigate the mechanisms involved in RBC clearance and the recycling of their iron.
Experiments in mice revealed that the presence of damaged RBCs in the bloodstream led to a rapid increase in a specific population of monocytes. These cells took up the damaged RBCs and traveled to both the liver and the spleen.
Several hours later, almost all of those RBCs were located within a population of specialized macrophages that were observed only in the liver. Those macrophages eventually disappeared once they were no longer needed.
The researchers also showed that expression of chemokines draws RBC-ingesting monocytes to the liver, resulting in the accumulation of the iron-recycling macrophages.
Blocking that process led to several indicators of impaired RBC clearance, including toxic levels of free iron and hemoglobin and signs of liver and kidney damage.
“The fact that the liver is the main organ of RBC removal and iron recycling is surprising, as is the fact that the liver relies on a buffer system consisting of bone marrow-derived monocytes that consume damaged red blood cells in the blood and settle in the liver, where they become the transient macrophages capable of iron recycling,” Dr Swirski said.
“The mechanism we identified could be either helpful or damaging, depending on the conditions. If overactive, it could remove too many RBCs, but if it’s sluggish or otherwise impaired, it could lead to iron toxicity. Further study could provide us with details of how this mechanism occurs in the first place and help us understand how to harness or suppress it in various conditions.”
Drug may be curative for certain HL patients
Photo from Business Wire
Five-year follow-up data from a phase 2 trial indicate that a subset of Hodgkin lymphoma (HL) patients who fail autologous stem cell transplant can achieve long-term disease control with single-agent brentuximab vedotin and may potentially be cured.
Thirty-three percent of patients in this trial achieved a complete remission (CR) with brentuximab vedotin, 13% remained in CR for more than 5 years, and 9% remained in CR without receiving a consolidative allogeneic transplant.
These results were published in Blood. The trial was sponsored by Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.
“At the time of trial initiation, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant,” said study author Robert Chen, MD, of City of Hope National Medical Center in Duarte, California.
“The median survival of the patients on [brentuximab vedotin] monotherapy in this pivotal phase 2 trial exceeds these historic figures, and I am pleased to see the publication of the final data.”
Dr Chen previously reported results from this trial at the 2010 ASH Annual Meeting.
The single-arm trial, which supported the US approval of brentuximab vedotin in 2011, was conducted in 102 patients with relapsed or refractory classical HL. The patients’ median age was 31 (range, 15-77), they had an ECOG status of 0 or 1, and both genders were represented equally.
The patients had received a median of 3.5 chemotherapy regimens (range, 1-13), 66% had received prior radiation, and all patients had received an autologous transplant. Seventy-one percent of patients were refractory to frontline therapy, and 42% were refractory to their most recent treatment.
The patients received brentuximab vedotin intravenously at 1.8 mg/kg every 21 days for a maximum of 16 cycles.
Results
Thirty-four patients (33%) achieved a CR. At the 5-year follow-up and end of the study, the median duration of response was not reached.
Thirteen of the 34 patients (38%) who achieved a CR remained in remission at study closure. Of these patients, 4 underwent consolidative allogeneic stem cell transplants while in remission, and 9 received no further therapy.
Among the patients who achieved a CR, the estimated 5-year overall survival (OS) rate was 64%, and the estimated 5-year progression-free survival (PFS) rate was 52%.
For the entire study cohort, the median OS was 40.5 months, and the median PFS was 9.3 months. The estimated 5-year OS was 41%, and the estimated 5-year PFS was 22%.
The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea.
Treatment-emergent peripheral neuropathy occurred in 56 patients (55%). Eighty-eight percent of these patients had an improvement in their symptoms, and 73% had complete resolution of peripheral neuropathy.
Photo from Business Wire
Five-year follow-up data from a phase 2 trial indicate that a subset of Hodgkin lymphoma (HL) patients who fail autologous stem cell transplant can achieve long-term disease control with single-agent brentuximab vedotin and may potentially be cured.
Thirty-three percent of patients in this trial achieved a complete remission (CR) with brentuximab vedotin, 13% remained in CR for more than 5 years, and 9% remained in CR without receiving a consolidative allogeneic transplant.
These results were published in Blood. The trial was sponsored by Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.
“At the time of trial initiation, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant,” said study author Robert Chen, MD, of City of Hope National Medical Center in Duarte, California.
“The median survival of the patients on [brentuximab vedotin] monotherapy in this pivotal phase 2 trial exceeds these historic figures, and I am pleased to see the publication of the final data.”
Dr Chen previously reported results from this trial at the 2010 ASH Annual Meeting.
The single-arm trial, which supported the US approval of brentuximab vedotin in 2011, was conducted in 102 patients with relapsed or refractory classical HL. The patients’ median age was 31 (range, 15-77), they had an ECOG status of 0 or 1, and both genders were represented equally.
The patients had received a median of 3.5 chemotherapy regimens (range, 1-13), 66% had received prior radiation, and all patients had received an autologous transplant. Seventy-one percent of patients were refractory to frontline therapy, and 42% were refractory to their most recent treatment.
The patients received brentuximab vedotin intravenously at 1.8 mg/kg every 21 days for a maximum of 16 cycles.
Results
Thirty-four patients (33%) achieved a CR. At the 5-year follow-up and end of the study, the median duration of response was not reached.
Thirteen of the 34 patients (38%) who achieved a CR remained in remission at study closure. Of these patients, 4 underwent consolidative allogeneic stem cell transplants while in remission, and 9 received no further therapy.
Among the patients who achieved a CR, the estimated 5-year overall survival (OS) rate was 64%, and the estimated 5-year progression-free survival (PFS) rate was 52%.
For the entire study cohort, the median OS was 40.5 months, and the median PFS was 9.3 months. The estimated 5-year OS was 41%, and the estimated 5-year PFS was 22%.
The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea.
Treatment-emergent peripheral neuropathy occurred in 56 patients (55%). Eighty-eight percent of these patients had an improvement in their symptoms, and 73% had complete resolution of peripheral neuropathy.
Photo from Business Wire
Five-year follow-up data from a phase 2 trial indicate that a subset of Hodgkin lymphoma (HL) patients who fail autologous stem cell transplant can achieve long-term disease control with single-agent brentuximab vedotin and may potentially be cured.
Thirty-three percent of patients in this trial achieved a complete remission (CR) with brentuximab vedotin, 13% remained in CR for more than 5 years, and 9% remained in CR without receiving a consolidative allogeneic transplant.
These results were published in Blood. The trial was sponsored by Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin.
“At the time of trial initiation, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant,” said study author Robert Chen, MD, of City of Hope National Medical Center in Duarte, California.
“The median survival of the patients on [brentuximab vedotin] monotherapy in this pivotal phase 2 trial exceeds these historic figures, and I am pleased to see the publication of the final data.”
Dr Chen previously reported results from this trial at the 2010 ASH Annual Meeting.
The single-arm trial, which supported the US approval of brentuximab vedotin in 2011, was conducted in 102 patients with relapsed or refractory classical HL. The patients’ median age was 31 (range, 15-77), they had an ECOG status of 0 or 1, and both genders were represented equally.
The patients had received a median of 3.5 chemotherapy regimens (range, 1-13), 66% had received prior radiation, and all patients had received an autologous transplant. Seventy-one percent of patients were refractory to frontline therapy, and 42% were refractory to their most recent treatment.
The patients received brentuximab vedotin intravenously at 1.8 mg/kg every 21 days for a maximum of 16 cycles.
Results
Thirty-four patients (33%) achieved a CR. At the 5-year follow-up and end of the study, the median duration of response was not reached.
Thirteen of the 34 patients (38%) who achieved a CR remained in remission at study closure. Of these patients, 4 underwent consolidative allogeneic stem cell transplants while in remission, and 9 received no further therapy.
Among the patients who achieved a CR, the estimated 5-year overall survival (OS) rate was 64%, and the estimated 5-year progression-free survival (PFS) rate was 52%.
For the entire study cohort, the median OS was 40.5 months, and the median PFS was 9.3 months. The estimated 5-year OS was 41%, and the estimated 5-year PFS was 22%.
The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea.
Treatment-emergent peripheral neuropathy occurred in 56 patients (55%). Eighty-eight percent of these patients had an improvement in their symptoms, and 73% had complete resolution of peripheral neuropathy.
Combo doesn’t improve PFS in DLBCL
Results of a phase 3 study suggest that obinutuzumab may not confer a benefit over standard therapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The data showed that obinutuzumab plus CHOP chemotherapy does not improve progression-free survival (PFS) in DLBCL patients, when compared to rituximab plus CHOP.
Adverse events with both treatment regimens were consistent with those seen in previous clinical trials, according to Genentech and Biogen, the companies developing obinutuzumab.
The companies have not released any data from this trial, known as GOYA, but they said results will be presented at an upcoming medical meeting.
“Two previous studies showed [obinutuzumab] helped people with previously untreated follicular lymphoma or chronic lymphocytic leukemia live longer without their disease worsening compared to [rituximab], when each was combined with chemotherapy,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech.
“We were hopeful we could show a similar result for people with diffuse large B-cell lymphoma and once again improve on the standard of care. We will continue to analyze the GOYA data to better understand the results, and to study other investigational treatments in this disease with the goal of further helping these patients.”
The GOYA trial enrolled 1418 previously untreated patients with CD20-positive DLBCL. The patients were randomized to receive obinutuzumab at 1000 mg every 21 days or rituximab at 375 mg/m2 every 21 days for 8 cycles, in addition to 6 to 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 21 days.
The primary endpoint of the study is investigator-assessed PFS, with secondary endpoints including PFS assessed by an independent review committee, response rate, overall survival, disease-free survival, and safety profile.
Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20, a protein found on certain B cells. The drug is thought to work by attacking targeted cells both directly and together with the immune system.
In the US and the European Union (EU), obinutuzumab is approved for use in combination with chlorambucil to treat adults with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved in the US and the EU to treat patients with follicular lymphoma. The drug can be given, first in combination with bendamustine and then alone as maintenance therapy, to adults with follicular lymphoma who did not respond to a rituximab-containing regimen or whose disease returned after such treatment.
Obinutuzumab is marketed as Gazyvaro in the EU and Switzerland and Gazyva in the rest of the world.
Results of a phase 3 study suggest that obinutuzumab may not confer a benefit over standard therapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The data showed that obinutuzumab plus CHOP chemotherapy does not improve progression-free survival (PFS) in DLBCL patients, when compared to rituximab plus CHOP.
Adverse events with both treatment regimens were consistent with those seen in previous clinical trials, according to Genentech and Biogen, the companies developing obinutuzumab.
The companies have not released any data from this trial, known as GOYA, but they said results will be presented at an upcoming medical meeting.
“Two previous studies showed [obinutuzumab] helped people with previously untreated follicular lymphoma or chronic lymphocytic leukemia live longer without their disease worsening compared to [rituximab], when each was combined with chemotherapy,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech.
“We were hopeful we could show a similar result for people with diffuse large B-cell lymphoma and once again improve on the standard of care. We will continue to analyze the GOYA data to better understand the results, and to study other investigational treatments in this disease with the goal of further helping these patients.”
The GOYA trial enrolled 1418 previously untreated patients with CD20-positive DLBCL. The patients were randomized to receive obinutuzumab at 1000 mg every 21 days or rituximab at 375 mg/m2 every 21 days for 8 cycles, in addition to 6 to 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 21 days.
The primary endpoint of the study is investigator-assessed PFS, with secondary endpoints including PFS assessed by an independent review committee, response rate, overall survival, disease-free survival, and safety profile.
Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20, a protein found on certain B cells. The drug is thought to work by attacking targeted cells both directly and together with the immune system.
In the US and the European Union (EU), obinutuzumab is approved for use in combination with chlorambucil to treat adults with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved in the US and the EU to treat patients with follicular lymphoma. The drug can be given, first in combination with bendamustine and then alone as maintenance therapy, to adults with follicular lymphoma who did not respond to a rituximab-containing regimen or whose disease returned after such treatment.
Obinutuzumab is marketed as Gazyvaro in the EU and Switzerland and Gazyva in the rest of the world.
Results of a phase 3 study suggest that obinutuzumab may not confer a benefit over standard therapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The data showed that obinutuzumab plus CHOP chemotherapy does not improve progression-free survival (PFS) in DLBCL patients, when compared to rituximab plus CHOP.
Adverse events with both treatment regimens were consistent with those seen in previous clinical trials, according to Genentech and Biogen, the companies developing obinutuzumab.
The companies have not released any data from this trial, known as GOYA, but they said results will be presented at an upcoming medical meeting.
“Two previous studies showed [obinutuzumab] helped people with previously untreated follicular lymphoma or chronic lymphocytic leukemia live longer without their disease worsening compared to [rituximab], when each was combined with chemotherapy,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech.
“We were hopeful we could show a similar result for people with diffuse large B-cell lymphoma and once again improve on the standard of care. We will continue to analyze the GOYA data to better understand the results, and to study other investigational treatments in this disease with the goal of further helping these patients.”
The GOYA trial enrolled 1418 previously untreated patients with CD20-positive DLBCL. The patients were randomized to receive obinutuzumab at 1000 mg every 21 days or rituximab at 375 mg/m2 every 21 days for 8 cycles, in addition to 6 to 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 21 days.
The primary endpoint of the study is investigator-assessed PFS, with secondary endpoints including PFS assessed by an independent review committee, response rate, overall survival, disease-free survival, and safety profile.
Obinutuzumab is an engineered monoclonal antibody designed to attach to CD20, a protein found on certain B cells. The drug is thought to work by attacking targeted cells both directly and together with the immune system.
In the US and the European Union (EU), obinutuzumab is approved for use in combination with chlorambucil to treat adults with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved in the US and the EU to treat patients with follicular lymphoma. The drug can be given, first in combination with bendamustine and then alone as maintenance therapy, to adults with follicular lymphoma who did not respond to a rituximab-containing regimen or whose disease returned after such treatment.
Obinutuzumab is marketed as Gazyvaro in the EU and Switzerland and Gazyva in the rest of the world.
Guidelines cut costs, reduce waste of donated blood
Photo courtesy of UAB Hospital
SAN DIEGO—Blood management guidelines can save millions of dollars and drastically reduce the waste of donated blood, according to a group of investigators.
A team at Vanderbilt University Medical Center in Nashville, Tennessee, developed blood utilization practice guidelines that resulted in $2 million in savings and a 30% reduction in blood use from 2011 to 2015.
The investigators presented these results in a poster at the 2016 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) Conference.
“The transfusion committee at Vanderbilt was interested in evaluating how we could implement evidence-based guidelines around restrictive transfusion,” said investigator Barbara J. Martin, RN.
To that end, the team first decided to change the standard practice of ordering 2 units of blood per patient. The investigators modified the medical center’s computerized provider order entry system to allow for blood ordering to be based on a specific assessment of each case, rather than a standard order of 2 units.
This change reduced red blood cell transfusions by more than 30%—from 675 units per 1000 discharges in 2011 to 432 units per 1000 discharges in 2015.
The investigators also noted that, for general and vascular surgery patients who underwent NSQIP- targeted procedures—including colectomy, proctectomy, ventral hernia, and appendectomy—between 5% and 6% were transfused with an average of 2.4 units of blood per patient in 2015.
In comparison, 11% of such patients were transfused with an average of 4.6 units of blood per patient in 2011.
“We found that, in that particular population, many of whom are transfused for acute blood loss, we still saw a significant decrease in the number of units transfused into the patient,” Martin said.
In addition to addressing blood utilization, the investigators developed guidelines to reduce waste. These guidelines state that, when more than 1 unit of blood is ordered, it must be sent in a cooler rather than the pneumatic tube. Coolers were reconfigured to optimize temperature management.
Furthermore, a specific member of the staff is tasked with “ownership” of the blood products, including returning unused product to the blood bank. Finally, individual unit wastage is reported to clinical leaders for review, and aggregate data are reported monthly.
The use of these guidelines resulted in fewer than 80 units of blood being wasted in 2015, down from 300 units in 2011.
Martin said the guidelines she and her colleagues developed could easily be implemented at other medical centers.
“Blood is a limited resource,” she noted, “and we have a responsibility as a healthcare provider to optimize the use of a resource that is difficult to get and only available through altruistic donations.”
Photo courtesy of UAB Hospital
SAN DIEGO—Blood management guidelines can save millions of dollars and drastically reduce the waste of donated blood, according to a group of investigators.
A team at Vanderbilt University Medical Center in Nashville, Tennessee, developed blood utilization practice guidelines that resulted in $2 million in savings and a 30% reduction in blood use from 2011 to 2015.
The investigators presented these results in a poster at the 2016 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) Conference.
“The transfusion committee at Vanderbilt was interested in evaluating how we could implement evidence-based guidelines around restrictive transfusion,” said investigator Barbara J. Martin, RN.
To that end, the team first decided to change the standard practice of ordering 2 units of blood per patient. The investigators modified the medical center’s computerized provider order entry system to allow for blood ordering to be based on a specific assessment of each case, rather than a standard order of 2 units.
This change reduced red blood cell transfusions by more than 30%—from 675 units per 1000 discharges in 2011 to 432 units per 1000 discharges in 2015.
The investigators also noted that, for general and vascular surgery patients who underwent NSQIP- targeted procedures—including colectomy, proctectomy, ventral hernia, and appendectomy—between 5% and 6% were transfused with an average of 2.4 units of blood per patient in 2015.
In comparison, 11% of such patients were transfused with an average of 4.6 units of blood per patient in 2011.
“We found that, in that particular population, many of whom are transfused for acute blood loss, we still saw a significant decrease in the number of units transfused into the patient,” Martin said.
In addition to addressing blood utilization, the investigators developed guidelines to reduce waste. These guidelines state that, when more than 1 unit of blood is ordered, it must be sent in a cooler rather than the pneumatic tube. Coolers were reconfigured to optimize temperature management.
Furthermore, a specific member of the staff is tasked with “ownership” of the blood products, including returning unused product to the blood bank. Finally, individual unit wastage is reported to clinical leaders for review, and aggregate data are reported monthly.
The use of these guidelines resulted in fewer than 80 units of blood being wasted in 2015, down from 300 units in 2011.
Martin said the guidelines she and her colleagues developed could easily be implemented at other medical centers.
“Blood is a limited resource,” she noted, “and we have a responsibility as a healthcare provider to optimize the use of a resource that is difficult to get and only available through altruistic donations.”
Photo courtesy of UAB Hospital
SAN DIEGO—Blood management guidelines can save millions of dollars and drastically reduce the waste of donated blood, according to a group of investigators.
A team at Vanderbilt University Medical Center in Nashville, Tennessee, developed blood utilization practice guidelines that resulted in $2 million in savings and a 30% reduction in blood use from 2011 to 2015.
The investigators presented these results in a poster at the 2016 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) Conference.
“The transfusion committee at Vanderbilt was interested in evaluating how we could implement evidence-based guidelines around restrictive transfusion,” said investigator Barbara J. Martin, RN.
To that end, the team first decided to change the standard practice of ordering 2 units of blood per patient. The investigators modified the medical center’s computerized provider order entry system to allow for blood ordering to be based on a specific assessment of each case, rather than a standard order of 2 units.
This change reduced red blood cell transfusions by more than 30%—from 675 units per 1000 discharges in 2011 to 432 units per 1000 discharges in 2015.
The investigators also noted that, for general and vascular surgery patients who underwent NSQIP- targeted procedures—including colectomy, proctectomy, ventral hernia, and appendectomy—between 5% and 6% were transfused with an average of 2.4 units of blood per patient in 2015.
In comparison, 11% of such patients were transfused with an average of 4.6 units of blood per patient in 2011.
“We found that, in that particular population, many of whom are transfused for acute blood loss, we still saw a significant decrease in the number of units transfused into the patient,” Martin said.
In addition to addressing blood utilization, the investigators developed guidelines to reduce waste. These guidelines state that, when more than 1 unit of blood is ordered, it must be sent in a cooler rather than the pneumatic tube. Coolers were reconfigured to optimize temperature management.
Furthermore, a specific member of the staff is tasked with “ownership” of the blood products, including returning unused product to the blood bank. Finally, individual unit wastage is reported to clinical leaders for review, and aggregate data are reported monthly.
The use of these guidelines resulted in fewer than 80 units of blood being wasted in 2015, down from 300 units in 2011.
Martin said the guidelines she and her colleagues developed could easily be implemented at other medical centers.
“Blood is a limited resource,” she noted, “and we have a responsibility as a healthcare provider to optimize the use of a resource that is difficult to get and only available through altruistic donations.”
Proposed Medicare physician fee schedule update ‘a great foundation’ – ACP
First impressions of the Centers for Medicare & Medicaid Services’ proposed updated to the physician fee schedule for 2017 are positive, according to the American College of Physicians.
“We think it’s a great foundation,” Robert B. Doherty, ACP senior vice president of government affairs and public policy, said in an interview.
The proposed update, published July 15 in the Federal Register, brings in a number of new policies aimed at improving physician payment for caring for patients with multiple chronic conditions; mental and behavioral health issues; and cognitive impairment or mobility-related issues.
Among the provisions in the 800+-page proposal, are revised billing codes that would more accurately recognize the work of primary care and other cognitive specialties. The changes, according to CMS, will help “better identify and value primary care, care management, and cognitive services.” Comments on the proposed rule are due Sept. 6, 2016.
The agency is proposing a number of coding changes that “could improve health care delivery for all types of services holding the most promise for healthier people and smarter spending, and advance our health equity goals,” according to a CMS fact sheet.
The proposed fee schedule also would update how quality is measured and reported by accountable care organizations in the Medicare Shared Savings Program; align Accountable Care Organization reporting with the Physician Quality Reporting System; and change how beneficiaries are assigned to an ACO. Potentially misvalued services also would continue to be reviewed under the proposal.
“We think this is a big step forward,” Mr. Doherty said. “There is a lot in this proposed rule to strengthen primary care and particularly to reduce barriers to the ability of primary care physicians to take care of patients with chronic illnesses and patients who have mental or behavioral health conditions.”
“There are a number of specific provisions we are very happy to see in the proposed rule, including improvements in the existing codes for chronic care management, creating new codes for more complex chronic care management, simplifying the billing for those codes, creating reimbursement for a team-based primary and behavioral health care services, expansion of a program to help prevent diabetes and patients who are at high risk of developing diabetes and a whole host of other things,” he continued, adding that upon first inspection, there was nothing that stood out as being a proposal that they were not happy with, though he expects when ACP staff drills deeper into the details, the organization will make recommendations to better strengthen the overall proposal.
The agency is also proposing a code to allow for the payment of advanced care planning services furnished via telehealth.
First impressions of the Centers for Medicare & Medicaid Services’ proposed updated to the physician fee schedule for 2017 are positive, according to the American College of Physicians.
“We think it’s a great foundation,” Robert B. Doherty, ACP senior vice president of government affairs and public policy, said in an interview.
The proposed update, published July 15 in the Federal Register, brings in a number of new policies aimed at improving physician payment for caring for patients with multiple chronic conditions; mental and behavioral health issues; and cognitive impairment or mobility-related issues.
Among the provisions in the 800+-page proposal, are revised billing codes that would more accurately recognize the work of primary care and other cognitive specialties. The changes, according to CMS, will help “better identify and value primary care, care management, and cognitive services.” Comments on the proposed rule are due Sept. 6, 2016.
The agency is proposing a number of coding changes that “could improve health care delivery for all types of services holding the most promise for healthier people and smarter spending, and advance our health equity goals,” according to a CMS fact sheet.
The proposed fee schedule also would update how quality is measured and reported by accountable care organizations in the Medicare Shared Savings Program; align Accountable Care Organization reporting with the Physician Quality Reporting System; and change how beneficiaries are assigned to an ACO. Potentially misvalued services also would continue to be reviewed under the proposal.
“We think this is a big step forward,” Mr. Doherty said. “There is a lot in this proposed rule to strengthen primary care and particularly to reduce barriers to the ability of primary care physicians to take care of patients with chronic illnesses and patients who have mental or behavioral health conditions.”
“There are a number of specific provisions we are very happy to see in the proposed rule, including improvements in the existing codes for chronic care management, creating new codes for more complex chronic care management, simplifying the billing for those codes, creating reimbursement for a team-based primary and behavioral health care services, expansion of a program to help prevent diabetes and patients who are at high risk of developing diabetes and a whole host of other things,” he continued, adding that upon first inspection, there was nothing that stood out as being a proposal that they were not happy with, though he expects when ACP staff drills deeper into the details, the organization will make recommendations to better strengthen the overall proposal.
The agency is also proposing a code to allow for the payment of advanced care planning services furnished via telehealth.
First impressions of the Centers for Medicare & Medicaid Services’ proposed updated to the physician fee schedule for 2017 are positive, according to the American College of Physicians.
“We think it’s a great foundation,” Robert B. Doherty, ACP senior vice president of government affairs and public policy, said in an interview.
The proposed update, published July 15 in the Federal Register, brings in a number of new policies aimed at improving physician payment for caring for patients with multiple chronic conditions; mental and behavioral health issues; and cognitive impairment or mobility-related issues.
Among the provisions in the 800+-page proposal, are revised billing codes that would more accurately recognize the work of primary care and other cognitive specialties. The changes, according to CMS, will help “better identify and value primary care, care management, and cognitive services.” Comments on the proposed rule are due Sept. 6, 2016.
The agency is proposing a number of coding changes that “could improve health care delivery for all types of services holding the most promise for healthier people and smarter spending, and advance our health equity goals,” according to a CMS fact sheet.
The proposed fee schedule also would update how quality is measured and reported by accountable care organizations in the Medicare Shared Savings Program; align Accountable Care Organization reporting with the Physician Quality Reporting System; and change how beneficiaries are assigned to an ACO. Potentially misvalued services also would continue to be reviewed under the proposal.
“We think this is a big step forward,” Mr. Doherty said. “There is a lot in this proposed rule to strengthen primary care and particularly to reduce barriers to the ability of primary care physicians to take care of patients with chronic illnesses and patients who have mental or behavioral health conditions.”
“There are a number of specific provisions we are very happy to see in the proposed rule, including improvements in the existing codes for chronic care management, creating new codes for more complex chronic care management, simplifying the billing for those codes, creating reimbursement for a team-based primary and behavioral health care services, expansion of a program to help prevent diabetes and patients who are at high risk of developing diabetes and a whole host of other things,” he continued, adding that upon first inspection, there was nothing that stood out as being a proposal that they were not happy with, though he expects when ACP staff drills deeper into the details, the organization will make recommendations to better strengthen the overall proposal.
The agency is also proposing a code to allow for the payment of advanced care planning services furnished via telehealth.
Peter Chin, MD
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Ceritinib effective when NSCLC progresses despite crizotinib
Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.
Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.
They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.
After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.
Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).
No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.
Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.
Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.
They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.
After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.
Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).
No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.
Ceritinib produced clinically meaningful, durable responses in patients who had advanced non–small-cell lung cancer and a history of multiple treatments with chemotherapies and crizotinib, according to investigators.
Ceritinib was effective even in patients with brain metastases, and it both reduced a high tumor burden and improved lung symptoms, said Lucio Crino, MD, of the University Medical School of Perugia (Italy) and his associates.
They assessed ceritinib in a single-arm, open-label, phase II trial involving 140 adults with advanced ALK-rearranged non–small-cell lung cancer at 51 sites worldwide who had received at least two lines of antineoplastic chemotherapy and had progressed while taking crizotinib. A total of 100 patients (72%) had brain metastases.
After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6% and the disease control rate was 77.1%. Tumor burden was significantly reduced in 75.2% of patients. Treatment response was rapid, occurring at a median of 1.8 months, and durable, lasting for a median of 9.7 months. Median progression-free survival was 5.7 months, median overall survival was 14.9 months, and the 1-year overall survival rate was 63.8%.
Treatment response was similar in the subgroup of patients who had brain metastases at baseline: Their overall response rate was 33.0%, the disease control rate was 74.0%, the median duration of response was 9.2 months, and median progression-free survival was 5.4 months (J Clin Oncol. 2016 July 17. doi: 10.1200/JCO.2015.65.5936).
No new or unexpected adverse events occurred. All patients reported at least one adverse event, most commonly nausea, diarrhea, and vomiting. Most adverse events were managed without dose interruption or reduction. There was a trend toward improvement in lung symptoms such as cough, pain, and dyspnea, and both health-related quality of life and functional capacity were generally maintained throughout ceritinib treatment, Dr. Crino and his associates said.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Ceritinib produced meaningful, durable responses in heavily pretreated patients with NSCLC who had advanced disease, including brain metastases.
Major finding: After a median follow-up of 11 months (range, 0-19 months), the overall response rate was 38.6%, the disease control rate was 77.1%, and the overall survival rate was 63.8%.
Data source: A single-arm open-label multicenter phase II trial involving 140 patients whose NSCLC progressed despite multiple treatments including crizotinib.
Disclosures: Novartis supported the study. Dr. Crino reported receiving honoraria from and consulting for Novartis, Eli Lilly, AstraZeneca, Pfizer, and Roche; his associates reported ties to numerous industry sources.
Delaying surgery for 11 weeks after RCT does not increase pCR rates for rectal cancer
Among patients with rectal cancer, delaying surgery for 11 weeks after the end of radiochemotherapy does not improve pathologic complete response rates, investigators reported.
Previously, the Lyon trial, the only randomized controlled study to investigate the effects of delaying surgery following the end of radiochemotherapy (RCT), found that compared with a 2-week delay, a 6-week delay significantly increased the number of patients who experienced complete response (53.1% vs. 71.7%, P = .007). The purpose of the current study was to evaluate the effect of a longer interval between RCT and surgery on pathologic complete response (pCR) rates.
For the phase III, multicenter, randomized trial, 265 patients with mid or lower rectal cancer were randomized to receive surgery at 7 weeks (n = 133) or 11 weeks (n = 132) following the end of RCT.
Baseline tumor characteristics and patient demographics were similar between the two study arms; the majority of patients had stage cT3 rectal cancer (82%).
There was no significant difference in pathologic complete response rate between the study arms (15% for 7-week group vs. 17.4% for 11-week group, P = .5983), reported Jeremie Lefevre, MD, of Hopital Saint-Antoine, Paris, and his associates (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.6049).
Overall morbidity was significantly increased in the 11-week group (44.5% v 32%; P = .04), primarily explained by an increase in medical complications (32.8% vs. 19.2%; P = .01), the investigators wrote.
The French Ministry of Health funded the study. Dr. Lefevre and seven of his associates reported serving in advisory roles, receiving financial compensation, or participating in the speakers bureau for multiple companies.
On Twitter @jessnicolecraig
Among patients with rectal cancer, delaying surgery for 11 weeks after the end of radiochemotherapy does not improve pathologic complete response rates, investigators reported.
Previously, the Lyon trial, the only randomized controlled study to investigate the effects of delaying surgery following the end of radiochemotherapy (RCT), found that compared with a 2-week delay, a 6-week delay significantly increased the number of patients who experienced complete response (53.1% vs. 71.7%, P = .007). The purpose of the current study was to evaluate the effect of a longer interval between RCT and surgery on pathologic complete response (pCR) rates.
For the phase III, multicenter, randomized trial, 265 patients with mid or lower rectal cancer were randomized to receive surgery at 7 weeks (n = 133) or 11 weeks (n = 132) following the end of RCT.
Baseline tumor characteristics and patient demographics were similar between the two study arms; the majority of patients had stage cT3 rectal cancer (82%).
There was no significant difference in pathologic complete response rate between the study arms (15% for 7-week group vs. 17.4% for 11-week group, P = .5983), reported Jeremie Lefevre, MD, of Hopital Saint-Antoine, Paris, and his associates (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.6049).
Overall morbidity was significantly increased in the 11-week group (44.5% v 32%; P = .04), primarily explained by an increase in medical complications (32.8% vs. 19.2%; P = .01), the investigators wrote.
The French Ministry of Health funded the study. Dr. Lefevre and seven of his associates reported serving in advisory roles, receiving financial compensation, or participating in the speakers bureau for multiple companies.
On Twitter @jessnicolecraig
Among patients with rectal cancer, delaying surgery for 11 weeks after the end of radiochemotherapy does not improve pathologic complete response rates, investigators reported.
Previously, the Lyon trial, the only randomized controlled study to investigate the effects of delaying surgery following the end of radiochemotherapy (RCT), found that compared with a 2-week delay, a 6-week delay significantly increased the number of patients who experienced complete response (53.1% vs. 71.7%, P = .007). The purpose of the current study was to evaluate the effect of a longer interval between RCT and surgery on pathologic complete response (pCR) rates.
For the phase III, multicenter, randomized trial, 265 patients with mid or lower rectal cancer were randomized to receive surgery at 7 weeks (n = 133) or 11 weeks (n = 132) following the end of RCT.
Baseline tumor characteristics and patient demographics were similar between the two study arms; the majority of patients had stage cT3 rectal cancer (82%).
There was no significant difference in pathologic complete response rate between the study arms (15% for 7-week group vs. 17.4% for 11-week group, P = .5983), reported Jeremie Lefevre, MD, of Hopital Saint-Antoine, Paris, and his associates (J Clin Oncol. 2016 July. doi: 10.1200/JCO.2016.67.6049).
Overall morbidity was significantly increased in the 11-week group (44.5% v 32%; P = .04), primarily explained by an increase in medical complications (32.8% vs. 19.2%; P = .01), the investigators wrote.
The French Ministry of Health funded the study. Dr. Lefevre and seven of his associates reported serving in advisory roles, receiving financial compensation, or participating in the speakers bureau for multiple companies.
On Twitter @jessnicolecraig
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Delaying surgery for 11 weeks after the end of radiochemotherapy does not improve pathologic complete response rates in patients with rectal cancer, compared with a delay of 7 weeks.
Major finding: There was no significant difference in pathologic complete response rate between the study arms (15% for 7-week group vs. 17.4% for 11-week group, P = .5983).
Data source: A phase III, multicenter, randomized trial involving 265 patients with varying stages of rectal cancer.
Disclosures: The French Ministry of Health funded the study. Dr. Lefevre and seven of his associates reported serving in advisory roles, receiving financial compensation, or participating in the speakers bureau for multiple companies.