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VIDEO: Checkpoint inhibitors show few efficacy, safety differences
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
[email protected]
On Twitter @mitchelzoler
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This very important systematic review with data from a total of nearly 6,000 patients shows that severe toxicity is unusual with the PD-1 and PD-L1 inhibitors, and they result in no meaningful difference in response rates. The toxicities seen with these drugs are milder and less frequent than we see with standard chemotherapy drugs. The severe autoimmune toxicities seen are a major concern but are manageable and occurred at low rates.
In general, efficacy and toxicity does not appear to form a basis by which to choose among these drugs. Fatigue was the most common adverse event, which is surprising to see with these drugs although we are accustomed to seeing it in patients on standard chemotherapy. Fatigue can be a major issue for patients, even if it is relatively mild, because they remain on these drugs for periods as long as 2 years.
If the PD-1 and PD-L1 inhibitors continue to perform with similar efficacy and safety profiles, clinicians will be forced to turn to other parameters when trying to decide which drug specifically to prescribe. This can include issues of cost, reimbursement, and dosing convenience. Nivolumab, for example, has been administered more often, every 2 weeks, than the other drugs in these classes. Oncologists are trying to develop effective regimens with these drugs that can be given once every 3 or every 4 weeks. Future investigations may also look at the possibility of treating patients with these drugs initially for 6 months, and then scaling back to retreatment only when there is disease progression. If this approach is successful, it would obviate concerns about causing long-term fatigue or the inconvenience of more frequent treatment schedules.
We also need to continue to monitor and compare the toxicities of these immune checkpoint inhibitors as we move into using them in combination regimens.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Merck/MSD, Merck Serono, and Roche, and he has received honoraria from Merck and Roche, and he has received travel grants from BMS and Roche. He made these comments as the designated discussant for the report and in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
[email protected]
On Twitter @mitchelzoler
VIENNA – The two subclasses of immune checkpoint inhibitor drugs showed very little basis for choosing between them by either efficacy or toxicity in a systematic review of 23 trials run in patients with non–small cell lung cancer during 2013-2016.
For efficacy, inhibitors of the programmed death (PD-1) receptors had a 19% overall response rate when averaged from 12 different trials with 3,284 patients on one of these drugs. The PD-ligand 1 (PD-L1) inhibitors produced a 17% overall response rate in 11 trials with 2,615 patients on one of the drugs, a between-class efficacy difference that was not statistically significant, Rathi N. Pillai, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
Immune-related adverse events were significantly more common in the patients treated with PD-1 inhibitors: 16%, compared with 11% in the PD-L1 inhibitor-treated patients (P = .04). The two subclasses also showed a trend toward a difference in the most common immune-related adverse event, hypothyroidism, with an incidence of 6.7% with PD-1 inhibitors and 4.2% with PD-L1 inhibitors (P = .07). The two sets of patients showed a statistically significant difference in the next most common immune-related adverse event, pneunomitis, 4.0% with PD-1 inhibitors and 2.0% with PD-L1 inhibitors (P = .02).
The trials with PD-1 inhibitors included nivolumab (Opdivo) and pembrolizumab (Keytruda). The trials with PD-L1 inhibitors included atezolizumab (Tecentriq), durvalumab, and avelumab. The total rate of all adverse events was highest among patients on nivolumab, 76%, and lowest among patients on durvalumab, 61%.
[email protected]
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: Overall response rates were 19% using a PD-1 inhibitor and 17% when using a PD-L1 inhibitor.
Data source: A systematic review of 23 trials in patients with non–small cell lung cancer published during 2013-2016.
Disclosures: Dr. Pillai had no disclosures.
Nivolumab plus ipilimumab shines as first-line in advanced NSCLC
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
VIENNA – The combination of nivolumab and ipilimumab as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) doubled median progression-free survival time compared with nivolumab monotherapy in updated results from the CheckMate 012 trial, Scott N. Gettinger, MD, reported at the World Congress on Lung Cancer.
This doubling of progression-free survival (PFS) applied to all comers regardless of whether or not their tumor expressed programmed death-ligand 1 (PD-L1). In those patients with any degree of PD-L1 expression – even if just 1% of tumor cells stained positive – combination therapy didn’t just double median PFS, it tripled it, compared with nivolumab alone, added Dr. Gettinger of the Yale Cancer Center in New Haven, Conn.
CheckMate 012 is a phase I study of nivolumab as first-line therapy for advanced NSCLC with numerous treatment arms. Dr. Gettinger presented updated results for 52 patients who received intravenous nivolumab monotherapy at a dose of 3 mg/kg every 2 weeks, 36 patients on nivolumab plus intravenous ipilimumab at 1 mg/kg every 12 weeks, and 39 who received nivolumab plus ipilimumab every 6 weeks. None of the participants had prior chemotherapy for their advanced stage IIIb or IV NSCLC.
Median PFS in the overall study population was 3.6 months with nivolumab monotherapy and 8.0 months with combination therapy. In the roughly 70% of participants who had any degree of tumor PD-L1 expression, median PFS was 3.5 months with monotherapy, compared with 12.7 months in the combined dual therapy arms. And, in the roughly one-quarter of patients whose tumor showed at least 50% PD-L1 expression, median PFS rose to 8.3 months with nivolumab monotherapy and hasn’t yet been reached in patients on combination therapy.
The 1-year overall survival rate in patients on nivolumab monotherapy was 73% in all treated patients, 69% in those with any detectable tumor PD-L1 expression, and 83% in patients with at least 50% PD-L1 expression. In patients on combination therapy, the corresponding figures were higher at 76%, 87%, and 100%.
The clearly enhanced efficacy achieved with the combination of nivolumab plus ipilimumab was accomplished with only a modest increase in toxicity compared with nivolumab alone. At a median follow-up of 22 months in the nivolumab monotherapy group and 16 months for combination therapy, the rate of any treatment-related adverse event leading to study withdrawal was 12% with monotherapy and 18% with combination therapy.
The combination of nivolumab (Opdivo), a PD-L1 immune checkpoint inhibitor, and ipilimumab (Yervoy), a cytotoxic T-lymphocyte–associated protein 4 immune checkpoint inhibitor, is biologically attractive: “The ipilimumab primes the immune system by inducing tumor infiltration of effector T cells while depleting the number of myeloid-derived suppressor cells and suppressive regulatory T cells within the tumor microenvironment,” Dr. Gettinger explained.
Nivolumab is approved for treatment of advanced NSCLC that has progressed despite platinum-based chemotherapy. Of the various toxicities associated with the drug, only dermatologic and GI adverse events occurred more frequently with combination therapy than nivolumab alone.
There were five complete responses in the nivolumab monotherapy group and six with combination therapy. Of note, four of these complete responses occurred in patients without any measurable tumor PD-L1 expression.
Based upon these encouraging results from CheckMate 012, a phase III randomized clinical trial of nivolumab as first-line therapy in patients with advanced NSCLC is underway. In the CheckMate 227 trial, patients with any detectable PD-L1 expression are randomized to nivolumab at 3mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks, nivolumab monotherapy at 240 mg every 2 weeks, or standard platinum-based chemotherapy. Patients with no PD-L1 expression in their tumor are assigned to the nivolumab/ipilimumab combination, or nivolumab at 360 mg every 3 weeks plus chemotherapy, or chemotherapy alone.
“I think we should be cautious despite the excitement about the combination,” argued Dr. Garon, director of thoracic oncology at the University of California, Los Angeles.
He noted that various iterations of the large CheckMate 012 phase I program have been presented repeatedly at major meetings, and the shifting data have raised concerns in his mind about possible patient selection bias stemming from the study design.
“From my perspective, until we see randomized data that can control for these biases, I will remain hopeful but not yet extremely confident that this combination will be the new frontline therapy for metastatic non–small cell lung cancer,” Dr. Garon said.
Dr. Gettinger reported serving as a consultant to Bristol-Myers Squibb, which markets nivolumab.
Dr. Garon reported that his institution receives funding from Bristol-Myers Squibb as well as AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Mirati, Merck, Pfizer, and Novartis.
AT WCLC 2016
Key clinical point: A combination of two immunotherapy agents with different mechanisms of action produced impressive efficacy and acceptable toxicities as first-line therapy in patients with chemotherapy-naive advanced non–small cell lung cancer.
Major finding: in patients with any detectable tumor PD-L1 expression.
Data source: This analysis from a larger phase I study included 127 patients with no prior chemotherapy for advanced NSCLC.
Disclosures: The study presenter is a consultant to Bristol-Myers Squibb, which sponsored the CheckMate 012 trial.
Chronic Cough in Children: Is it Asthma?
Tumor markers may predict anti–PD-L1 treatment response
NATIONAL HARBOR, MD. – Density in tumors of two key immune cells may be a biomarker for response to an inhibitor of programmed death–ligand 1 (PD-L1) among patients with non–small cell lung cancer (NSCLC).
Patients with NSCLC whose tumors bore high densities of both CD8-positive cytotoxic T lymphocytes and PD-L1 had significantly better outcomes when treated with the investigational PD-L1 inhibitor durvalumab than patients with high densities of either cell type alone, reported Sonja Althammer, PhD, a scientist at Definiens AG, maker of the anti–PD-L1 compound.
Dr. Althammer and her colleagues assessed the use of an automated image analysis and pattern recognition system to determine whether tumor-infiltrating CD8-positive cytotoxic T lymphocytes and PD-L1 densities could identify patients most likely to respond to the investigational PD-L1 inhibitor durvalumab.
“The hypothesis that we had in mind was that the interaction between both cell populations is important, so both cell populations should be present,” she said.
The investigators analyzed archived or fresh tumor biopsy samples from 163 patients with untreated or previously treated NSCLC (median 3 prior lines of therapy) who were enrolled in a nonrandomized phase I/II trial evaluating durvalumab in advanced NSCLC and other solid tumors.
They matched CD8 and PD-L1 immunohistochemistry-stained sections from tissues blocks. High PD-L1 expression was defined as a 25% or higher proportion of PD-L1–positive tumor cells with membrane staining at any intensity.
The images were then evaluated with an automated system, with results matched to clinical outcomes based on the densities of CD8-positive and PD-L1–positive cells, and PD-L1 alone from pre-treatment biopsy samples using a discovery set (84 samples) and validation set (79). The datasets were matched on baseline PD-L1 status, histology, Eastern Cooperative Oncology Group performance status, lines of therapy, and response.
In a training set looking at overall response rate (ORR), they found evidence to suggest that the combination of CD8 and PD-L1 positivity was associated with a higher ORR: 42%, compared with 31% for CD8-positive expression alone, 27% for PD-L1–positive alone, and 7% for CD8-positive PD-L1–negative (less than 25% expression) alone.
They then examined the predictive ability of the combined markers, and found that over approximately 28 months of follow-up, patients with CD8-positive and PD-L1–positive dense tumors had better overall survival (median overall survival, 24.3 months), compared with PD-L1–positive only patients (median overall survival, 17.1 months), CD8-positive only patients (median overall survival, 17.8 months), or the entire patient sample (median overall survival, 11.1 months).
Similarly, progression-free survival was also better among patients with high expression of both markers (respective median progression-free survival was 7.3, 3.6, 5.3, and 2.8 months).
Dr. Althammer acknowledged that the findings were preliminary and needed to be confirmed independently in larger studies.
The study was supported by MedImmune. Sonja Althammer is an employee of Definiens AG, which is a subsidiary of MedImmune/AstraZeneca.
NATIONAL HARBOR, MD. – Density in tumors of two key immune cells may be a biomarker for response to an inhibitor of programmed death–ligand 1 (PD-L1) among patients with non–small cell lung cancer (NSCLC).
Patients with NSCLC whose tumors bore high densities of both CD8-positive cytotoxic T lymphocytes and PD-L1 had significantly better outcomes when treated with the investigational PD-L1 inhibitor durvalumab than patients with high densities of either cell type alone, reported Sonja Althammer, PhD, a scientist at Definiens AG, maker of the anti–PD-L1 compound.
Dr. Althammer and her colleagues assessed the use of an automated image analysis and pattern recognition system to determine whether tumor-infiltrating CD8-positive cytotoxic T lymphocytes and PD-L1 densities could identify patients most likely to respond to the investigational PD-L1 inhibitor durvalumab.
“The hypothesis that we had in mind was that the interaction between both cell populations is important, so both cell populations should be present,” she said.
The investigators analyzed archived or fresh tumor biopsy samples from 163 patients with untreated or previously treated NSCLC (median 3 prior lines of therapy) who were enrolled in a nonrandomized phase I/II trial evaluating durvalumab in advanced NSCLC and other solid tumors.
They matched CD8 and PD-L1 immunohistochemistry-stained sections from tissues blocks. High PD-L1 expression was defined as a 25% or higher proportion of PD-L1–positive tumor cells with membrane staining at any intensity.
The images were then evaluated with an automated system, with results matched to clinical outcomes based on the densities of CD8-positive and PD-L1–positive cells, and PD-L1 alone from pre-treatment biopsy samples using a discovery set (84 samples) and validation set (79). The datasets were matched on baseline PD-L1 status, histology, Eastern Cooperative Oncology Group performance status, lines of therapy, and response.
In a training set looking at overall response rate (ORR), they found evidence to suggest that the combination of CD8 and PD-L1 positivity was associated with a higher ORR: 42%, compared with 31% for CD8-positive expression alone, 27% for PD-L1–positive alone, and 7% for CD8-positive PD-L1–negative (less than 25% expression) alone.
They then examined the predictive ability of the combined markers, and found that over approximately 28 months of follow-up, patients with CD8-positive and PD-L1–positive dense tumors had better overall survival (median overall survival, 24.3 months), compared with PD-L1–positive only patients (median overall survival, 17.1 months), CD8-positive only patients (median overall survival, 17.8 months), or the entire patient sample (median overall survival, 11.1 months).
Similarly, progression-free survival was also better among patients with high expression of both markers (respective median progression-free survival was 7.3, 3.6, 5.3, and 2.8 months).
Dr. Althammer acknowledged that the findings were preliminary and needed to be confirmed independently in larger studies.
The study was supported by MedImmune. Sonja Althammer is an employee of Definiens AG, which is a subsidiary of MedImmune/AstraZeneca.
NATIONAL HARBOR, MD. – Density in tumors of two key immune cells may be a biomarker for response to an inhibitor of programmed death–ligand 1 (PD-L1) among patients with non–small cell lung cancer (NSCLC).
Patients with NSCLC whose tumors bore high densities of both CD8-positive cytotoxic T lymphocytes and PD-L1 had significantly better outcomes when treated with the investigational PD-L1 inhibitor durvalumab than patients with high densities of either cell type alone, reported Sonja Althammer, PhD, a scientist at Definiens AG, maker of the anti–PD-L1 compound.
Dr. Althammer and her colleagues assessed the use of an automated image analysis and pattern recognition system to determine whether tumor-infiltrating CD8-positive cytotoxic T lymphocytes and PD-L1 densities could identify patients most likely to respond to the investigational PD-L1 inhibitor durvalumab.
“The hypothesis that we had in mind was that the interaction between both cell populations is important, so both cell populations should be present,” she said.
The investigators analyzed archived or fresh tumor biopsy samples from 163 patients with untreated or previously treated NSCLC (median 3 prior lines of therapy) who were enrolled in a nonrandomized phase I/II trial evaluating durvalumab in advanced NSCLC and other solid tumors.
They matched CD8 and PD-L1 immunohistochemistry-stained sections from tissues blocks. High PD-L1 expression was defined as a 25% or higher proportion of PD-L1–positive tumor cells with membrane staining at any intensity.
The images were then evaluated with an automated system, with results matched to clinical outcomes based on the densities of CD8-positive and PD-L1–positive cells, and PD-L1 alone from pre-treatment biopsy samples using a discovery set (84 samples) and validation set (79). The datasets were matched on baseline PD-L1 status, histology, Eastern Cooperative Oncology Group performance status, lines of therapy, and response.
In a training set looking at overall response rate (ORR), they found evidence to suggest that the combination of CD8 and PD-L1 positivity was associated with a higher ORR: 42%, compared with 31% for CD8-positive expression alone, 27% for PD-L1–positive alone, and 7% for CD8-positive PD-L1–negative (less than 25% expression) alone.
They then examined the predictive ability of the combined markers, and found that over approximately 28 months of follow-up, patients with CD8-positive and PD-L1–positive dense tumors had better overall survival (median overall survival, 24.3 months), compared with PD-L1–positive only patients (median overall survival, 17.1 months), CD8-positive only patients (median overall survival, 17.8 months), or the entire patient sample (median overall survival, 11.1 months).
Similarly, progression-free survival was also better among patients with high expression of both markers (respective median progression-free survival was 7.3, 3.6, 5.3, and 2.8 months).
Dr. Althammer acknowledged that the findings were preliminary and needed to be confirmed independently in larger studies.
The study was supported by MedImmune. Sonja Althammer is an employee of Definiens AG, which is a subsidiary of MedImmune/AstraZeneca.
AT SITC 2016
Key clinical point: Tumor expression of two cell types may predict responses to anti–PD-L1 immunotherapy.
Major finding: High tumor densities of CD8-postive cytotoxic T lymphocytes and the programmed death-ligand 1 were associated with improved overall response rates and survival in patients with advanced non–small cell lung cancer treated with a PD-L1 inhibitor.
Data source: Imaging study of samples from 163 patients enrolled in a nonrandomized phase I/II trial.
Disclosures: The study was supported by MedImmune. Sonja Althammer is an employee of Definiens AG, which is a subsidiary of MedImmune/AstraZeneca.
Kaiser experience: A helping hand reduces COPD readmissions
LOS ANGELES – With a handful of common-sense steps, the Kaiser Permanente Los Angeles Medical Center reduced 30-day hospital readmissions for chronic obstructive pulmonary disease (COPD) from 17.4/1,000 in Dec. 2013 to 11.9/1,000 in Dec. 2015.
The 57 readmissions avoided in 2015 saved the medical center $700,359, according to a report at the annual meeting of the American College of Chest Physicians.
The quality improvement project – dubbed KP Breath – started in 2013 after staff realized their COPD readmission rates were significantly higher than other area hospitals, and likely to increase. “We knew we had a problem, and that if we did not address it, it was going to be out of control,” Mr. Cam said. There was also the risk of Centers for Medicare & Medicaid Services penalties for COPD readmissions.
Mr. Cam and his colleagues discovered several problems. “Leaving the hospital, [COPD patients] didn’t know what medication was for what, or their medication schedule. They didn’t know how to use their inhalers, and didn’t understand what the disease process was all about, and what it was doing to them,” he said.
There was little continuity of care after discharge; many patients didn’t even have a pulmonologist. Essentially, COPD patients were lost to follow-up until they returned to the emergency department with another exacerbation.
A rapid Plan, Do, Study, Act cycle was the first step; it identified solutions that would work based on COPD management guidelines and published studies. “They were all things that have been shown to reduce rehospitalizations,” said pulmonologist Luis Moreta-Sainz, MD, another key project member.
The team staggered their changes over 2 years. Pulmonary consults for acute exacerbation admissions shot up, and respiratory therapists started to stop by to educate almost every COPD patient about medication use, trigger avoidance, and other matters. Patients began watching educational videos from their bed.
Changes were made after discharge, too. “We felt strongly that pulmonary rehabilitation needed to be an integral part of care, and that patients had to be connected to the pulmonary clinic,” Dr. Moreta-Sainz said.
Patients were booked for a pulmonologist at the clinic soon after they left the hospital, and greeted there by their COPD navigator – a respiratory therapist operating at the top of their license – who bridged the gap between inpatient and outpatient care and oversaw their case, helping with medical, psychosocial, and palliative needs.
Patients were also channeled into pulmonary rehab, three sessions per week for 6-8 weeks, with additional sessions as needed. The outpatient education emphasized and expanded the inpatient lessons, and patients exercised on treadmills and other equipment. They learned how to use resistance bands at home to increase upper body strength and decrease disability. Kaiser increased the number of weekly pulmonary rehab slots from 8 to 64 to make it happen.
After rehab, patients were offered a pedometer to measure how many steps they walked, and a phone number to report it each day. Those who participated got a call from the navigator when they fell below targets.
It has all made a huge difference. Dr. Moreta-Sainz said he’d like to add in-home visits and family support groups, so caregivers know what to do if things head south.
The work was funded by Kaiser; Dr. Moreta-Sainz and Mr. Cam have no disclosures.
[email protected]
On a recent morning, two of my scheduled clinic patients were “no-shows.” Both of them were patients with COPD that I had recently cared for in-hospital for an exacerbation. While I know that snow may have played a role, there are other barriers to care, including lack of access to transportation, poor health literacy, and no effective health insurance.
On a recent morning, two of my scheduled clinic patients were “no-shows.” Both of them were patients with COPD that I had recently cared for in-hospital for an exacerbation. While I know that snow may have played a role, there are other barriers to care, including lack of access to transportation, poor health literacy, and no effective health insurance.
On a recent morning, two of my scheduled clinic patients were “no-shows.” Both of them were patients with COPD that I had recently cared for in-hospital for an exacerbation. While I know that snow may have played a role, there are other barriers to care, including lack of access to transportation, poor health literacy, and no effective health insurance.
LOS ANGELES – With a handful of common-sense steps, the Kaiser Permanente Los Angeles Medical Center reduced 30-day hospital readmissions for chronic obstructive pulmonary disease (COPD) from 17.4/1,000 in Dec. 2013 to 11.9/1,000 in Dec. 2015.
The 57 readmissions avoided in 2015 saved the medical center $700,359, according to a report at the annual meeting of the American College of Chest Physicians.
The quality improvement project – dubbed KP Breath – started in 2013 after staff realized their COPD readmission rates were significantly higher than other area hospitals, and likely to increase. “We knew we had a problem, and that if we did not address it, it was going to be out of control,” Mr. Cam said. There was also the risk of Centers for Medicare & Medicaid Services penalties for COPD readmissions.
Mr. Cam and his colleagues discovered several problems. “Leaving the hospital, [COPD patients] didn’t know what medication was for what, or their medication schedule. They didn’t know how to use their inhalers, and didn’t understand what the disease process was all about, and what it was doing to them,” he said.
There was little continuity of care after discharge; many patients didn’t even have a pulmonologist. Essentially, COPD patients were lost to follow-up until they returned to the emergency department with another exacerbation.
A rapid Plan, Do, Study, Act cycle was the first step; it identified solutions that would work based on COPD management guidelines and published studies. “They were all things that have been shown to reduce rehospitalizations,” said pulmonologist Luis Moreta-Sainz, MD, another key project member.
The team staggered their changes over 2 years. Pulmonary consults for acute exacerbation admissions shot up, and respiratory therapists started to stop by to educate almost every COPD patient about medication use, trigger avoidance, and other matters. Patients began watching educational videos from their bed.
Changes were made after discharge, too. “We felt strongly that pulmonary rehabilitation needed to be an integral part of care, and that patients had to be connected to the pulmonary clinic,” Dr. Moreta-Sainz said.
Patients were booked for a pulmonologist at the clinic soon after they left the hospital, and greeted there by their COPD navigator – a respiratory therapist operating at the top of their license – who bridged the gap between inpatient and outpatient care and oversaw their case, helping with medical, psychosocial, and palliative needs.
Patients were also channeled into pulmonary rehab, three sessions per week for 6-8 weeks, with additional sessions as needed. The outpatient education emphasized and expanded the inpatient lessons, and patients exercised on treadmills and other equipment. They learned how to use resistance bands at home to increase upper body strength and decrease disability. Kaiser increased the number of weekly pulmonary rehab slots from 8 to 64 to make it happen.
After rehab, patients were offered a pedometer to measure how many steps they walked, and a phone number to report it each day. Those who participated got a call from the navigator when they fell below targets.
It has all made a huge difference. Dr. Moreta-Sainz said he’d like to add in-home visits and family support groups, so caregivers know what to do if things head south.
The work was funded by Kaiser; Dr. Moreta-Sainz and Mr. Cam have no disclosures.
[email protected]
LOS ANGELES – With a handful of common-sense steps, the Kaiser Permanente Los Angeles Medical Center reduced 30-day hospital readmissions for chronic obstructive pulmonary disease (COPD) from 17.4/1,000 in Dec. 2013 to 11.9/1,000 in Dec. 2015.
The 57 readmissions avoided in 2015 saved the medical center $700,359, according to a report at the annual meeting of the American College of Chest Physicians.
The quality improvement project – dubbed KP Breath – started in 2013 after staff realized their COPD readmission rates were significantly higher than other area hospitals, and likely to increase. “We knew we had a problem, and that if we did not address it, it was going to be out of control,” Mr. Cam said. There was also the risk of Centers for Medicare & Medicaid Services penalties for COPD readmissions.
Mr. Cam and his colleagues discovered several problems. “Leaving the hospital, [COPD patients] didn’t know what medication was for what, or their medication schedule. They didn’t know how to use their inhalers, and didn’t understand what the disease process was all about, and what it was doing to them,” he said.
There was little continuity of care after discharge; many patients didn’t even have a pulmonologist. Essentially, COPD patients were lost to follow-up until they returned to the emergency department with another exacerbation.
A rapid Plan, Do, Study, Act cycle was the first step; it identified solutions that would work based on COPD management guidelines and published studies. “They were all things that have been shown to reduce rehospitalizations,” said pulmonologist Luis Moreta-Sainz, MD, another key project member.
The team staggered their changes over 2 years. Pulmonary consults for acute exacerbation admissions shot up, and respiratory therapists started to stop by to educate almost every COPD patient about medication use, trigger avoidance, and other matters. Patients began watching educational videos from their bed.
Changes were made after discharge, too. “We felt strongly that pulmonary rehabilitation needed to be an integral part of care, and that patients had to be connected to the pulmonary clinic,” Dr. Moreta-Sainz said.
Patients were booked for a pulmonologist at the clinic soon after they left the hospital, and greeted there by their COPD navigator – a respiratory therapist operating at the top of their license – who bridged the gap between inpatient and outpatient care and oversaw their case, helping with medical, psychosocial, and palliative needs.
Patients were also channeled into pulmonary rehab, three sessions per week for 6-8 weeks, with additional sessions as needed. The outpatient education emphasized and expanded the inpatient lessons, and patients exercised on treadmills and other equipment. They learned how to use resistance bands at home to increase upper body strength and decrease disability. Kaiser increased the number of weekly pulmonary rehab slots from 8 to 64 to make it happen.
After rehab, patients were offered a pedometer to measure how many steps they walked, and a phone number to report it each day. Those who participated got a call from the navigator when they fell below targets.
It has all made a huge difference. Dr. Moreta-Sainz said he’d like to add in-home visits and family support groups, so caregivers know what to do if things head south.
The work was funded by Kaiser; Dr. Moreta-Sainz and Mr. Cam have no disclosures.
[email protected]
AT CHEST 2016
Interatrial shunt benefits sustained for 1 year in HFpEF patients
NEW ORLEANS – An interatrial septal shunt device continued to provide “sustained and meaningful clinical benefit” at 1-year follow-up for 64 patients who had heart failure with preserved ejection fraction (HFpEF), David M. Kaye, MD, PhD, reported at the American Heart Association scientific sessions.
The device is implanted via cardiac catheterization and is intended to reduce elevated left atrial pressure, particularly that associated with exertion, by allowing a small amount but not excessive left-to-right shunting. Patients showed improvements in 6-minute walk distance, New York Heart Association class, and HF-related quality of life scores at 6 months, and those effects persisted at the most recent (12-month) follow-up, he said in a presentation that was simultaneously published online in Circulation (2016 Nov 16).
Overall survival at 1 year was 95%. Three patients died (one from combined pneumonia and renal failure, one from a fatal stroke, and one from an undetermined cause) and one was lost to follow-up. Thirteen patients required 17 hospitalizations for heart failure.
Six-minute walk distance improved from 331 meters at baseline to 363 meters. NYHA classification improved dramatically, as did quality of life scores as assessed by the Minnesota Living with HF questionnaire.
All 48 devices that were evaluable on echocardiographic imaging remained patent, showing continued left-to-right shunting. Left ventricular ejection fraction remained unchanged while right ventricular ejection fraction was significantly elevated over baseline levels. “In conjunction, there were modest but stable reductions in LV end-diastolic volume index with a concomitant rise in RV end-diastolic index,” he said.
A subset of 18 study participants underwent heart catheterization during both rest and exercise so that hemodynamics could be assessed. Exercise time increased significantly, from 8.2 minutes at baseline to 9.7 minutes at 6 months and to 10.4 minutes at 1 year. Similarly, peak work capacity during supine cycling increased from 48 watts at baseline to 60 watts at 6 months and 55 watts at 1 year. These benefits occurred without any increase in pulmonary capillary wedge pressure.
Systemic blood pressure did not change over time, either at rest or during exercise. Left and right atrial volumes also remained unchanged.
Perhaps most importantly, Dr. Kaye said, right-sided cardiac output increased significantly, while left-sided cardiac output remained unchanged. There was no evidence of increased pulmonary pressure or pulmonary vascular resistance. This meant that patients could do more physical activity for a given level of left atrial pressure, he said.
Furthermore, 1-year mortality was lower in this trial, at 4.6%, than in the placebo groups of the I-PRESERVE trial in irbesartan (5.2%) and the U.S. group of the TOPCAT trial in spironolactone (7.7%), said Dr. Kaye, professor and chief of cardiology at the University of Arizona, Tuscon.
Device therapy could have an enormous impact in carefully selected patients with HFpEF, for whom there are no medical treatments, despite the nonrandomized nature of the trial.
REDUCE LAP-HF was funded by Corvia Medical, maker of the shunt device. Dr. Kaye is an unpaid member of Corvia’s scientific advisory group. Dr. Sweitzer is an investigator in the ongoing randomized trial of the interatrial shunt.
NEW ORLEANS – An interatrial septal shunt device continued to provide “sustained and meaningful clinical benefit” at 1-year follow-up for 64 patients who had heart failure with preserved ejection fraction (HFpEF), David M. Kaye, MD, PhD, reported at the American Heart Association scientific sessions.
The device is implanted via cardiac catheterization and is intended to reduce elevated left atrial pressure, particularly that associated with exertion, by allowing a small amount but not excessive left-to-right shunting. Patients showed improvements in 6-minute walk distance, New York Heart Association class, and HF-related quality of life scores at 6 months, and those effects persisted at the most recent (12-month) follow-up, he said in a presentation that was simultaneously published online in Circulation (2016 Nov 16).
Overall survival at 1 year was 95%. Three patients died (one from combined pneumonia and renal failure, one from a fatal stroke, and one from an undetermined cause) and one was lost to follow-up. Thirteen patients required 17 hospitalizations for heart failure.
Six-minute walk distance improved from 331 meters at baseline to 363 meters. NYHA classification improved dramatically, as did quality of life scores as assessed by the Minnesota Living with HF questionnaire.
All 48 devices that were evaluable on echocardiographic imaging remained patent, showing continued left-to-right shunting. Left ventricular ejection fraction remained unchanged while right ventricular ejection fraction was significantly elevated over baseline levels. “In conjunction, there were modest but stable reductions in LV end-diastolic volume index with a concomitant rise in RV end-diastolic index,” he said.
A subset of 18 study participants underwent heart catheterization during both rest and exercise so that hemodynamics could be assessed. Exercise time increased significantly, from 8.2 minutes at baseline to 9.7 minutes at 6 months and to 10.4 minutes at 1 year. Similarly, peak work capacity during supine cycling increased from 48 watts at baseline to 60 watts at 6 months and 55 watts at 1 year. These benefits occurred without any increase in pulmonary capillary wedge pressure.
Systemic blood pressure did not change over time, either at rest or during exercise. Left and right atrial volumes also remained unchanged.
Perhaps most importantly, Dr. Kaye said, right-sided cardiac output increased significantly, while left-sided cardiac output remained unchanged. There was no evidence of increased pulmonary pressure or pulmonary vascular resistance. This meant that patients could do more physical activity for a given level of left atrial pressure, he said.
Furthermore, 1-year mortality was lower in this trial, at 4.6%, than in the placebo groups of the I-PRESERVE trial in irbesartan (5.2%) and the U.S. group of the TOPCAT trial in spironolactone (7.7%), said Dr. Kaye, professor and chief of cardiology at the University of Arizona, Tuscon.
Device therapy could have an enormous impact in carefully selected patients with HFpEF, for whom there are no medical treatments, despite the nonrandomized nature of the trial.
REDUCE LAP-HF was funded by Corvia Medical, maker of the shunt device. Dr. Kaye is an unpaid member of Corvia’s scientific advisory group. Dr. Sweitzer is an investigator in the ongoing randomized trial of the interatrial shunt.
NEW ORLEANS – An interatrial septal shunt device continued to provide “sustained and meaningful clinical benefit” at 1-year follow-up for 64 patients who had heart failure with preserved ejection fraction (HFpEF), David M. Kaye, MD, PhD, reported at the American Heart Association scientific sessions.
The device is implanted via cardiac catheterization and is intended to reduce elevated left atrial pressure, particularly that associated with exertion, by allowing a small amount but not excessive left-to-right shunting. Patients showed improvements in 6-minute walk distance, New York Heart Association class, and HF-related quality of life scores at 6 months, and those effects persisted at the most recent (12-month) follow-up, he said in a presentation that was simultaneously published online in Circulation (2016 Nov 16).
Overall survival at 1 year was 95%. Three patients died (one from combined pneumonia and renal failure, one from a fatal stroke, and one from an undetermined cause) and one was lost to follow-up. Thirteen patients required 17 hospitalizations for heart failure.
Six-minute walk distance improved from 331 meters at baseline to 363 meters. NYHA classification improved dramatically, as did quality of life scores as assessed by the Minnesota Living with HF questionnaire.
All 48 devices that were evaluable on echocardiographic imaging remained patent, showing continued left-to-right shunting. Left ventricular ejection fraction remained unchanged while right ventricular ejection fraction was significantly elevated over baseline levels. “In conjunction, there were modest but stable reductions in LV end-diastolic volume index with a concomitant rise in RV end-diastolic index,” he said.
A subset of 18 study participants underwent heart catheterization during both rest and exercise so that hemodynamics could be assessed. Exercise time increased significantly, from 8.2 minutes at baseline to 9.7 minutes at 6 months and to 10.4 minutes at 1 year. Similarly, peak work capacity during supine cycling increased from 48 watts at baseline to 60 watts at 6 months and 55 watts at 1 year. These benefits occurred without any increase in pulmonary capillary wedge pressure.
Systemic blood pressure did not change over time, either at rest or during exercise. Left and right atrial volumes also remained unchanged.
Perhaps most importantly, Dr. Kaye said, right-sided cardiac output increased significantly, while left-sided cardiac output remained unchanged. There was no evidence of increased pulmonary pressure or pulmonary vascular resistance. This meant that patients could do more physical activity for a given level of left atrial pressure, he said.
Furthermore, 1-year mortality was lower in this trial, at 4.6%, than in the placebo groups of the I-PRESERVE trial in irbesartan (5.2%) and the U.S. group of the TOPCAT trial in spironolactone (7.7%), said Dr. Kaye, professor and chief of cardiology at the University of Arizona, Tuscon.
Device therapy could have an enormous impact in carefully selected patients with HFpEF, for whom there are no medical treatments, despite the nonrandomized nature of the trial.
REDUCE LAP-HF was funded by Corvia Medical, maker of the shunt device. Dr. Kaye is an unpaid member of Corvia’s scientific advisory group. Dr. Sweitzer is an investigator in the ongoing randomized trial of the interatrial shunt.
AT THE AHA SCIENTIFIC SESSIONS 2016
Key clinical point: An interatrial septal shunt device continued to provide sustained and meaningful clinical benefit at 1-year follow-up for 64 patients who had heart failure with preserved ejection fraction.
Major finding: Six-minute walk distance improved from 331 meters at baseline to 363 meters at 1 year, NYHA classification improved dramatically, and HF-related quality of life scores also improved.
Data source: REDUCE LAP-HF, a multicenter, prospective, open-label study involving 64 patients followed for 1 year after transcatheter implantation of a shunt device.
Disclosures: REDUCE LAP-HF was funded by Corvia Medical, maker of the shunt device. Dr. Kaye is an unpaid member of Corvia’s scientific advisory group.
Smoker has heart disease? Assess for COPD
What to assess before stepping up asthma therapy
Inhaled laninamivir reduces risk of influenza in young children
The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.
In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.
Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).
The treatment was also effective among children where the index case was infected with influenza A (H3N2).
Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.
The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.
Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.
“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”
The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.
Although vaccination remains the preferred approach for influenza prevention, additional options for influenza prophylaxis in children are important, given concerns for the emergence of resistance, the known antiviral adverse side effect profiles, possible limited supplies, and the potential for spotty patient compliance. This drug was well tolerated, without significant adverse events reported, and there were no neurologic symptoms or abnormal behavior, which have occurred with influenza illness and with other neuraminidase inhibitors in Japan.
Prompt initiation of influenza prophylaxis is necessary to ensure efficacy, which hinges on proper and prompt identification of index cases. Therefore, efforts to educate parents and families on the early signs and symptoms of influenza and the importance of seeking medical attention to confirm the diagnosis in the index case are crucial for timely initiation of prophylaxis in household contacts.
Flor M. Munoz, MD, is from the department of pediatrics at the Baylor College of Medicine and Texas Children’s Hospital in Houston, and Henry H. Bernstein, DO, is from the department of pediatrics, Hofstra Northwell School of Medicine, Hempstead, N.Y., and Cohen Children’s Medical Center of New York in New Hyde Park. These comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-2371). The authors reported having no relevant financial disclosures.
Although vaccination remains the preferred approach for influenza prevention, additional options for influenza prophylaxis in children are important, given concerns for the emergence of resistance, the known antiviral adverse side effect profiles, possible limited supplies, and the potential for spotty patient compliance. This drug was well tolerated, without significant adverse events reported, and there were no neurologic symptoms or abnormal behavior, which have occurred with influenza illness and with other neuraminidase inhibitors in Japan.
Prompt initiation of influenza prophylaxis is necessary to ensure efficacy, which hinges on proper and prompt identification of index cases. Therefore, efforts to educate parents and families on the early signs and symptoms of influenza and the importance of seeking medical attention to confirm the diagnosis in the index case are crucial for timely initiation of prophylaxis in household contacts.
Flor M. Munoz, MD, is from the department of pediatrics at the Baylor College of Medicine and Texas Children’s Hospital in Houston, and Henry H. Bernstein, DO, is from the department of pediatrics, Hofstra Northwell School of Medicine, Hempstead, N.Y., and Cohen Children’s Medical Center of New York in New Hyde Park. These comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-2371). The authors reported having no relevant financial disclosures.
Although vaccination remains the preferred approach for influenza prevention, additional options for influenza prophylaxis in children are important, given concerns for the emergence of resistance, the known antiviral adverse side effect profiles, possible limited supplies, and the potential for spotty patient compliance. This drug was well tolerated, without significant adverse events reported, and there were no neurologic symptoms or abnormal behavior, which have occurred with influenza illness and with other neuraminidase inhibitors in Japan.
Prompt initiation of influenza prophylaxis is necessary to ensure efficacy, which hinges on proper and prompt identification of index cases. Therefore, efforts to educate parents and families on the early signs and symptoms of influenza and the importance of seeking medical attention to confirm the diagnosis in the index case are crucial for timely initiation of prophylaxis in household contacts.
Flor M. Munoz, MD, is from the department of pediatrics at the Baylor College of Medicine and Texas Children’s Hospital in Houston, and Henry H. Bernstein, DO, is from the department of pediatrics, Hofstra Northwell School of Medicine, Hempstead, N.Y., and Cohen Children’s Medical Center of New York in New Hyde Park. These comments are adapted from an accompanying editorial (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-2371). The authors reported having no relevant financial disclosures.
The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.
In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.
Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).
The treatment was also effective among children where the index case was infected with influenza A (H3N2).
Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.
The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.
Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.
“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”
The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.
The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.
In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.
Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).
The treatment was also effective among children where the index case was infected with influenza A (H3N2).
Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.
The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.
Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.
“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”
The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.
FROM PEDIATRICS
Key clinical point:
Major finding: Children treated with laninamivir showed a 45.8% reduction in the risk of influenza, compared with the placebo group.
Data source: Randomized, double-blind, placebo-controlled trial in 343 children under 10 years old.
Disclosures: The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.
Inpatient telemedicine could bridge infectious disease specialist gap
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.