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Momelotinib hits the mark for deadly bone marrow cancer
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
FROM ASCO 2022
Promising treatment option for incurable lung cancer described as ‘significant’
, according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.
“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.
The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.
In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m2 and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.
At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).
The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.
The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.
This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).
, according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.
“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.
The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.
In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m2 and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.
At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).
The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.
The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.
This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).
, according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.
Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.
“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.
The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.
In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m2 and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.
At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).
The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.
The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.
This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).
FROM ASCO 2022
Severe COVID-19 and blood cancer: Plasma therapy may help
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
The study demonstrated that “plasma from convalescent or vaccinated individuals shortens the time to improvement in hematological and solid cancer patients with severe COVID-19” and “prolongs overall survival,” said study coauthor Maike Janssen, MD, of the department of internal medicine at Heidelberg (Germany) University Hospital.
Dr. Janssen presented the study findings at the annual congress of the European Hematology Association held in Vienna.
Although people with COVID-19 do not appear to benefit from treatment with convalescent plasma, some data indicate that certain patients who cannot mount a strong immune response to SARS-CoV-2 infection may benefit.
In this recent multicenter study, 134 patients with confirmed COVID-19 whose oxygen saturation was 94% or lower were randomly assigned to undergo treatment with convalescent or vaccinated SARS-CoV-2 plasma (n = 68) or to receive standard of care (n = 66). Patients fell into four clinical groups: those with a hematologic malignancy or who had undergone active cancer therapy for any cancer within the past 24 months; those with chronic immunosuppression; those between the ages of 50 and 75 with lymphopenia and/or elevated D-dimer levels; and those older than 75 years.
The convalescent or vaccinated SARS-CoV-2 plasma was administered in two bags (238-337 mL plasma each) from different donors on days 1 and 2. Only plasma from donors with high levels of neutralizing activity (titers above 1:80) were included. The primary endpoint was time to improvement by 2 points on a 7-point scale or discharge from the hospital. The secondary endpoint was improvement in overall survival.
The authors found that overall, patients in the plasma group demonstrated a shorter time to improvement – median of 12.5 days, vs. 18 days – but the difference was not significant (P = .29).
However, for the subgroup of 56 patients with hematologic/solid cancers, the time to improvement was significantly shorter: 13 days vs. 31 days (hazard ratio [HR], 2.5; P = .003).
Similarly, plasma therapy did not improve overall survival in the study population overall – there were 12 deaths in the plasma group over 80 days, vs. 15 in the control group (P = .80). Patients in the hematologic/solid cancer subgroup who received plasma therapy did demonstrate significantly better overall survival (HR, 0.28; P = .042).
No similar significant differences in time to improvement or overall survival were observed in the other three groups. “We found that plasma did not improve outcomes in immune-competent patients with other risk factors and/or older age,” Dr. Janssen said.
Although study enrollment ended when the Omicron variant began surging, Dr. Janssen noted that plasma from Omicron patients may also be of benefit to those with hematologic cancers.
“We have treated some patients in individual cases using plasma from Omicron patients who were already vaccinated or with breakthrough infections, and we did see benefits in those cases,” she noted.
The study was funded by the Federal Ministry of Education and Research, Germany. Dr. Janssen has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EHA 2022
Collagen ‘tile’ delivers postsurgical radiation in glioblastoma
and spares healthy tissue, new research suggests.
The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.
Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.
“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.
If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.
This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.
The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.
Radioactive seeds
GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.
The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.
Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.
The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.
GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.
It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.
“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.
With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.
Safety profile
The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.
“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.
Six participants had 0 6 -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.
The mean follow-up from initial diagnosis was 733 days (2 years).
Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.
Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.
He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.
As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.
“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”
One and done
Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.
In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.
The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.
Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.
“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.
A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.
“One of the beauties of this therapy is it’s a one-and-done deal,” he said.
Interesting, timely
Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”
These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.
“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.
However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.
In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.
Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.
The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and spares healthy tissue, new research suggests.
The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.
Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.
“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.
If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.
This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.
The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.
Radioactive seeds
GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.
The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.
Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.
The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.
GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.
It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.
“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.
With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.
Safety profile
The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.
“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.
Six participants had 0 6 -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.
The mean follow-up from initial diagnosis was 733 days (2 years).
Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.
Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.
He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.
As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.
“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”
One and done
Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.
In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.
The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.
Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.
“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.
A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.
“One of the beauties of this therapy is it’s a one-and-done deal,” he said.
Interesting, timely
Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”
These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.
“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.
However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.
In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.
Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.
The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
and spares healthy tissue, new research suggests.
The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.
Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.
“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.
If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.
This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.
The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.
Radioactive seeds
GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.
The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.
Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.
The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.
GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.
It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.
“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.
With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.
Safety profile
The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.
“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.
Six participants had 0 6 -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.
The mean follow-up from initial diagnosis was 733 days (2 years).
Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.
Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.
He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.
As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.
“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”
One and done
Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.
In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.
The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.
Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.
“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.
A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.
“One of the beauties of this therapy is it’s a one-and-done deal,” he said.
Interesting, timely
Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”
These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.
“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.
However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.
In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.
Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.
The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AANS 2022
Radiotherapy for brain metastases: ASTRO updates guidelines
“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.
“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.
The guideline was published May 6 in Practical Radiation Oncology.
“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.
“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.
Key recommendations
Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain, including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.
Key recommendations are as follows:
For patients with intact/unresected brain metastases:
- SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
- Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases.
- For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
- Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
- Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
- Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.
For patients with resected brain metastases:
- Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
- For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
- As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.
Updating the guidelines
ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.
The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.
A version of this article was first published on Medscape.com.
“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.
“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.
The guideline was published May 6 in Practical Radiation Oncology.
“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.
“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.
Key recommendations
Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain, including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.
Key recommendations are as follows:
For patients with intact/unresected brain metastases:
- SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
- Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases.
- For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
- Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
- Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
- Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.
For patients with resected brain metastases:
- Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
- For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
- As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.
Updating the guidelines
ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.
The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.
A version of this article was first published on Medscape.com.
“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.
“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.
The guideline was published May 6 in Practical Radiation Oncology.
“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.
“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.
Key recommendations
Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain, including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.
Key recommendations are as follows:
For patients with intact/unresected brain metastases:
- SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
- Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases.
- For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
- Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
- Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
- Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.
For patients with resected brain metastases:
- Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
- For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
- As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.
Updating the guidelines
ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.
The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.
A version of this article was first published on Medscape.com.
FROM PRACTICAL RADIATION ONCOLOGY
Acetaminophen linked to diminished response to immunotherapy in cancer
The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.
Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.
The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.
The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.
“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.
They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
Reconsider acetaminophen pretreatment
After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.
“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.
There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.
Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.
“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.
However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.
She was also unsure of how much acetaminophen is too much.
Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.
Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”
She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
Study details
Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.
All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.
In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).
None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).
In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).
A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.
There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.
A version of this article first appeared on Medscape.com.
The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.
Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.
The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.
The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.
“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.
They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
Reconsider acetaminophen pretreatment
After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.
“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.
There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.
Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.
“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.
However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.
She was also unsure of how much acetaminophen is too much.
Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.
Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”
She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
Study details
Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.
All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.
In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).
None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).
In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).
A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.
There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.
A version of this article first appeared on Medscape.com.
The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.
Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.
The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.
The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.
“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.
They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
Reconsider acetaminophen pretreatment
After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.
“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.
There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.
Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.
“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.
However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.
She was also unsure of how much acetaminophen is too much.
Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.
Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”
She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
Study details
Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.
All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.
In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).
None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).
In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).
A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.
There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022
‘Great optimism’ greets immunotherapy responses in dMMR rectal cancer
Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.
The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.
“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.
About 5%-10% of patients with rectal cancer have tumors with dMMR.
“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.
The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
Single-agent dostarlimab
For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.
Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.
All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.
For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.
As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.
“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”
To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.
In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.
Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.
The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
Editorial commentary
In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy.
For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”
Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.
“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.
“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.
In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.
The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.
The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.
In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”
The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others.
A version of this article first appeared on Medscape.com.
Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.
The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.
“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.
About 5%-10% of patients with rectal cancer have tumors with dMMR.
“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.
The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
Single-agent dostarlimab
For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.
Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.
All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.
For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.
As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.
“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”
To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.
In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.
Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.
The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
Editorial commentary
In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy.
For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”
Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.
“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.
“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.
In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.
The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.
The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.
In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”
The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others.
A version of this article first appeared on Medscape.com.
Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.
The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.
“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.
About 5%-10% of patients with rectal cancer have tumors with dMMR.
“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.
The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
Single-agent dostarlimab
For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.
Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.
All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.
For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.
As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.
“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”
To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.
In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.
Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.
The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
Editorial commentary
In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy.
For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”
Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.
“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.
“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.
In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.
The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.
The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.
In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”
The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022
Excess weight may ward off infection in breast cancer treatment
– a potentially deadly outcome that can occur as a result of chemotherapy treatment.
The study was presented at the annual meeting of the American Society of Clinical Oncology.
It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.
“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.
The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.
At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.
Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).
“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.
The analysis found no significant correlation between weight and occurrence of invasive disease events.
Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.
– a potentially deadly outcome that can occur as a result of chemotherapy treatment.
The study was presented at the annual meeting of the American Society of Clinical Oncology.
It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.
“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.
The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.
At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.
Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).
“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.
The analysis found no significant correlation between weight and occurrence of invasive disease events.
Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.
– a potentially deadly outcome that can occur as a result of chemotherapy treatment.
The study was presented at the annual meeting of the American Society of Clinical Oncology.
It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.
“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.
The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.
At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.
Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).
“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.
The analysis found no significant correlation between weight and occurrence of invasive disease events.
Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.
FROM ASCO 2022
Women with HER2+ metastatic breast cancer are living longer
When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.
Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.
“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.
The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.
“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.
A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).
Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.
A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.
This study was not funded.
When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.
Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.
“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.
The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.
“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.
A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).
Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.
A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.
This study was not funded.
When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.
Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.
“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.
The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.
“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.
A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).
Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.
A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.
This study was not funded.
FROM ASCO 2022
Panitumumab beats bevacizumab in left-sided mCRC
A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).
Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.
The overall survival benefit rose to 18% in those with left-sided tumors.
However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.
These findings come from the PARADIGM trial conducted in Japan.
The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.
“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.
“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.
Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”
commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.
The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.
Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”
These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.
Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.
In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.
Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.
There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.
Despite this, both antibody types continue to be used in these patients, he added.
PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).
The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).
After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).
In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).
However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.
Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.
There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.
These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.
He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.
At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.
Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.
In contrast, the remainder who survived for longer showed better outcomes with panitumumab.
Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.
Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.
However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.
Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.
The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.
A version of this article first appeared on Medscape.com.
A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).
Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.
The overall survival benefit rose to 18% in those with left-sided tumors.
However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.
These findings come from the PARADIGM trial conducted in Japan.
The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.
“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.
“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.
Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”
commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.
The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.
Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”
These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.
Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.
In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.
Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.
There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.
Despite this, both antibody types continue to be used in these patients, he added.
PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).
The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).
After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).
In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).
However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.
Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.
There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.
These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.
He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.
At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.
Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.
In contrast, the remainder who survived for longer showed better outcomes with panitumumab.
Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.
Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.
However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.
Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.
The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.
A version of this article first appeared on Medscape.com.
A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).
Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.
The overall survival benefit rose to 18% in those with left-sided tumors.
However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.
These findings come from the PARADIGM trial conducted in Japan.
The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.
“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.
“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.
Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”
commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.
The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.
Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”
These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.
Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.
In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.
Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.
There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.
Despite this, both antibody types continue to be used in these patients, he added.
PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).
The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).
After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).
In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).
However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.
Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.
There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.
These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.
He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.
At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.
Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.
In contrast, the remainder who survived for longer showed better outcomes with panitumumab.
Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.
Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.
However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.
Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.
The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.
A version of this article first appeared on Medscape.com.
FROM ASCO 2022