Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

Combination treatment strategies that include immunotherapeutic agents are expected to become the future of breast cancer treatment, according to a review.

“There is tremendous interest in using immunotherapy to treat breast cancer, as evidenced by the more than 290 clinical trials ongoing,” wrote Sylvia Adams, MD, MS, of New York University, along with her colleagues. The report is in JAMA Oncology.

“It is anticipated that combination therapy strategies will be the way forward for immunotherapy in breast cancer, with an improved understanding of tumor, microenvironment, and host factors informing treatment combination decisions, they said.

Dr. Adams and her colleagues searched major databases for clinical trials investigating the use of immunotherapy in both early-stage and metastatic breast cancer.

After the search, the team found that immune checkpoint blockade (ICB) agents were the most studied type of immunotherapy in breast cancer today.

In addition, Dr. Adams and her colleagues reported that when UCB agents were used as monotherapy in patients with breast cancer, objective responses have been seen, especially when given in the initial stages of treatment. “For responding patients, those responses are durable,” they added.

Recent findings have indicated that combining immune checkpoint blockade agents with chemotherapy may be useful in early breast cancer as neoadjuvant therapy.

“Combination trials were more common than single-agent studies, with the most commonly combined modalities being chemotherapy or targeted therapy,” the researchers wrote.

The review is limited by the rapid advancement of the current treatment landscape. As a result, additional data may now be available beyond the date of publication.

“Thoughtful study design incorporating appropriate end points and correlative studies will be critical in identifying optimal strategies for enhancing the immune response against breast tumors,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Amgen, Celgene, Genentech, Eli Lilly, Ipsen, Novartis, Pfizer, and several others.

SOURCE: Adams S et al. JAMA Oncol. 2019 Apr 11. doi: 10.1001/jamaoncol.2018.7147.

The SVS recently established the Section on Outpatient & Office Vascular Care (SOOVC) for clinicians who work in outpatient and office vascular care centers. SOOVC membership is available to all SVS members in good standing, and hospital/practice administrators are welcome to join as Affiliate Members. Benefits for SOOVC members include, but are not limited to, specific programming at the Vascular Annual Meeting, discounts on SVS events, networking opportunities and access to SVSConnect. Please reach out to soovc@vascularsociety.org or 312-334-2349 with questions. 

The SVS recently established the Section on Outpatient & Office Vascular Care (SOOVC) for clinicians who work in outpatient and office vascular care centers. SOOVC membership is available to all SVS members in good standing, and hospital/practice administrators are welcome to join as Affiliate Members. Benefits for SOOVC members include, but are not limited to, specific programming at the Vascular Annual Meeting, discounts on SVS events, networking opportunities and access to SVSConnect. Please reach out to soovc@vascularsociety.org or 312-334-2349 with questions. 

The SVS recently established the Section on Outpatient & Office Vascular Care (SOOVC) for clinicians who work in outpatient and office vascular care centers. SOOVC membership is available to all SVS members in good standing, and hospital/practice administrators are welcome to join as Affiliate Members. Benefits for SOOVC members include, but are not limited to, specific programming at the Vascular Annual Meeting, discounts on SVS events, networking opportunities and access to SVSConnect. Please reach out to soovc@vascularsociety.org or 312-334-2349 with questions. 

Begin planning your Vascular Annual Meeting experience today with the recently launched SVS Online Planner. This includes the entire VAM schedule, as well as the schedule for the Society for Vascular Nursing’s annual conference. The Vascular Quality Initiative’s meeting, VQI@VAM, will be available on the planner soon. With the Online Planner, you can easily search for information, such as presenters, specific topics, session types, intended audience and credit availability. It also makes creating a schedule simple and time-efficient. Access the online planner now.

Begin planning your Vascular Annual Meeting experience today with the recently launched SVS Online Planner. This includes the entire VAM schedule, as well as the schedule for the Society for Vascular Nursing’s annual conference. The Vascular Quality Initiative’s meeting, VQI@VAM, will be available on the planner soon. With the Online Planner, you can easily search for information, such as presenters, specific topics, session types, intended audience and credit availability. It also makes creating a schedule simple and time-efficient. Access the online planner now.

Begin planning your Vascular Annual Meeting experience today with the recently launched SVS Online Planner. This includes the entire VAM schedule, as well as the schedule for the Society for Vascular Nursing’s annual conference. The Vascular Quality Initiative’s meeting, VQI@VAM, will be available on the planner soon. With the Online Planner, you can easily search for information, such as presenters, specific topics, session types, intended audience and credit availability. It also makes creating a schedule simple and time-efficient. Access the online planner now.

The SVS is now seeking comments on draft Clinical Practice Guidelines on the Management of Visceral Aneurysms. Your comments are essential to strengthen the content of these guidelines, and to ensure relevance in clinical practice and potential for improvements in patient care. Feedback received during the comment period will be shared with the writing committee. Anyone, from SVS members to patients, is welcome to review these draft guidelines and provide comments before April 23.

The SVS is now seeking comments on draft Clinical Practice Guidelines on the Management of Visceral Aneurysms. Your comments are essential to strengthen the content of these guidelines, and to ensure relevance in clinical practice and potential for improvements in patient care. Feedback received during the comment period will be shared with the writing committee. Anyone, from SVS members to patients, is welcome to review these draft guidelines and provide comments before April 23.

The SVS is now seeking comments on draft Clinical Practice Guidelines on the Management of Visceral Aneurysms. Your comments are essential to strengthen the content of these guidelines, and to ensure relevance in clinical practice and potential for improvements in patient care. Feedback received during the comment period will be shared with the writing committee. Anyone, from SVS members to patients, is welcome to review these draft guidelines and provide comments before April 23.

VIENNA – The prevalence of liver steatosis among unselected English young adults was 21% in a study of just over 4,000 people. The prevalence of apparent liver fibrosis was 2.4%, and among the 21% with steatosis, nearly half – 10% of the studied cohort – had severe, S3 steatosis.

Mitchel L. Zoler/MDedge News

The prevalence of steatosis, a marker of nonalcoholic fatty liver disease (NAFLD), seemed to be linked with obesity. Among the 79% of the study group who had no steatosis the obesity prevalence was 6%, compared with a 26% prevalence among those with S1 steatosis, a 33% obesity rate among those with S2 steatosis, and a 57% obesity prevalence among those with S3 steatosis, Kushala Abeysekera, MBBS, said at the meeting sponsored by the European Association for the Study of the Liver.

He and his associates determined these prevalence rates in a population that excluded people who reported consuming what was deemed “excessive” alcohol use.

Another notable finding was that 1,874 of the same people had undergone ultrasound assessment for NAFLD when they were 18 years old, and that assessment found a prevalence of 2.5% (J Clin Endocrinol Metab. 2014 March;99[3]:e410-7), which meant that during the subsequent 6 years prevalence of NAFLD jumped nearly 900%.

Both the 2014 report and the current study used people who had been enrolled in the Avon Longitudinal Study of Parents and Children, a prospective population-based study that began by recruiting a cohort of more than 14,000 pregnant women during 1991-1992, and then followed the more than 13,000 children who resulted from those pregnancies. The study reported by Dr. Abeysekera focused on 4,021 of these children – now young adults – who responded to an invitation to participate in this follow-up, a number that then reduced to 3,600 with informative transient elastography results that quantified fibrosis, and 3,768 with valid Controlled Attenuated Parameter scores from elastography that reflected steatosis extent. Transient elastography is a noninvasive method of measuring liver stiffness using ultrasound and an elastic shear wave (Clin Mol Hepatol. 2012 June;18[2]:163-73).

“To the best of my knowledge, this is the only study that has assessed NAFLD in young adults using transient elastography,” said Dr. Abeysekera, an epidemiologist at the University of Bristol (England).

After subtracting from the study cohort people with excessive alcohol use, the study had transient elastography data from 3,277 24-year-olds that could calculate steatosis severity, and data from 3,128 that could quantify fibrosis.

The analysis also showed a statistically significant link between sex and the presence and severity of steatosis. Among women, 18% had steatosis, including 7% with S3 steatosis, defined as involving at least two-thirds of the liver. Among men, 26% had some degree of steatosis and 14% had the most severe form.

The presence of more severe liver fibrosis also showed a strong link to obesity. The eight people identified with F4 fibrosis (with cirrhosis) had a median body mass index of 32 kg/m2, compared with a median body mass index of 25 kg/m2 or less among those either without fibrosis or with a milder form of F1, F2, or F3 fibrosis.

Dr. Abeysekera reported no disclosures.

mzoler@mdedge.com

VIENNA – The prevalence of liver steatosis among unselected English young adults was 21% in a study of just over 4,000 people. The prevalence of apparent liver fibrosis was 2.4%, and among the 21% with steatosis, nearly half – 10% of the studied cohort – had severe, S3 steatosis.

Mitchel L. Zoler/MDedge News

The prevalence of steatosis, a marker of nonalcoholic fatty liver disease (NAFLD), seemed to be linked with obesity. Among the 79% of the study group who had no steatosis the obesity prevalence was 6%, compared with a 26% prevalence among those with S1 steatosis, a 33% obesity rate among those with S2 steatosis, and a 57% obesity prevalence among those with S3 steatosis, Kushala Abeysekera, MBBS, said at the meeting sponsored by the European Association for the Study of the Liver.

He and his associates determined these prevalence rates in a population that excluded people who reported consuming what was deemed “excessive” alcohol use.

Another notable finding was that 1,874 of the same people had undergone ultrasound assessment for NAFLD when they were 18 years old, and that assessment found a prevalence of 2.5% (J Clin Endocrinol Metab. 2014 March;99[3]:e410-7), which meant that during the subsequent 6 years prevalence of NAFLD jumped nearly 900%.

Both the 2014 report and the current study used people who had been enrolled in the Avon Longitudinal Study of Parents and Children, a prospective population-based study that began by recruiting a cohort of more than 14,000 pregnant women during 1991-1992, and then followed the more than 13,000 children who resulted from those pregnancies. The study reported by Dr. Abeysekera focused on 4,021 of these children – now young adults – who responded to an invitation to participate in this follow-up, a number that then reduced to 3,600 with informative transient elastography results that quantified fibrosis, and 3,768 with valid Controlled Attenuated Parameter scores from elastography that reflected steatosis extent. Transient elastography is a noninvasive method of measuring liver stiffness using ultrasound and an elastic shear wave (Clin Mol Hepatol. 2012 June;18[2]:163-73).

“To the best of my knowledge, this is the only study that has assessed NAFLD in young adults using transient elastography,” said Dr. Abeysekera, an epidemiologist at the University of Bristol (England).

After subtracting from the study cohort people with excessive alcohol use, the study had transient elastography data from 3,277 24-year-olds that could calculate steatosis severity, and data from 3,128 that could quantify fibrosis.

The analysis also showed a statistically significant link between sex and the presence and severity of steatosis. Among women, 18% had steatosis, including 7% with S3 steatosis, defined as involving at least two-thirds of the liver. Among men, 26% had some degree of steatosis and 14% had the most severe form.

The presence of more severe liver fibrosis also showed a strong link to obesity. The eight people identified with F4 fibrosis (with cirrhosis) had a median body mass index of 32 kg/m2, compared with a median body mass index of 25 kg/m2 or less among those either without fibrosis or with a milder form of F1, F2, or F3 fibrosis.

Dr. Abeysekera reported no disclosures.

mzoler@mdedge.com

VIENNA – The prevalence of liver steatosis among unselected English young adults was 21% in a study of just over 4,000 people. The prevalence of apparent liver fibrosis was 2.4%, and among the 21% with steatosis, nearly half – 10% of the studied cohort – had severe, S3 steatosis.

Mitchel L. Zoler/MDedge News

The prevalence of steatosis, a marker of nonalcoholic fatty liver disease (NAFLD), seemed to be linked with obesity. Among the 79% of the study group who had no steatosis the obesity prevalence was 6%, compared with a 26% prevalence among those with S1 steatosis, a 33% obesity rate among those with S2 steatosis, and a 57% obesity prevalence among those with S3 steatosis, Kushala Abeysekera, MBBS, said at the meeting sponsored by the European Association for the Study of the Liver.

He and his associates determined these prevalence rates in a population that excluded people who reported consuming what was deemed “excessive” alcohol use.

Another notable finding was that 1,874 of the same people had undergone ultrasound assessment for NAFLD when they were 18 years old, and that assessment found a prevalence of 2.5% (J Clin Endocrinol Metab. 2014 March;99[3]:e410-7), which meant that during the subsequent 6 years prevalence of NAFLD jumped nearly 900%.

Both the 2014 report and the current study used people who had been enrolled in the Avon Longitudinal Study of Parents and Children, a prospective population-based study that began by recruiting a cohort of more than 14,000 pregnant women during 1991-1992, and then followed the more than 13,000 children who resulted from those pregnancies. The study reported by Dr. Abeysekera focused on 4,021 of these children – now young adults – who responded to an invitation to participate in this follow-up, a number that then reduced to 3,600 with informative transient elastography results that quantified fibrosis, and 3,768 with valid Controlled Attenuated Parameter scores from elastography that reflected steatosis extent. Transient elastography is a noninvasive method of measuring liver stiffness using ultrasound and an elastic shear wave (Clin Mol Hepatol. 2012 June;18[2]:163-73).

“To the best of my knowledge, this is the only study that has assessed NAFLD in young adults using transient elastography,” said Dr. Abeysekera, an epidemiologist at the University of Bristol (England).

After subtracting from the study cohort people with excessive alcohol use, the study had transient elastography data from 3,277 24-year-olds that could calculate steatosis severity, and data from 3,128 that could quantify fibrosis.

The analysis also showed a statistically significant link between sex and the presence and severity of steatosis. Among women, 18% had steatosis, including 7% with S3 steatosis, defined as involving at least two-thirds of the liver. Among men, 26% had some degree of steatosis and 14% had the most severe form.

The presence of more severe liver fibrosis also showed a strong link to obesity. The eight people identified with F4 fibrosis (with cirrhosis) had a median body mass index of 32 kg/m2, compared with a median body mass index of 25 kg/m2 or less among those either without fibrosis or with a milder form of F1, F2, or F3 fibrosis.

Dr. Abeysekera reported no disclosures.

mzoler@mdedge.com

The Society for Vascular Surgery will provide complimentary meeting registration to a lucky attendee. To be eligible, all you must do is register for the meeting before 5 p.m. CDT Wednesday, April 24. The winner will be selected at random. This year’s meeting will be June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington D.C. Read more about the VAM contest, and more, in the latest SVS VAMail.

The Society for Vascular Surgery will provide complimentary meeting registration to a lucky attendee. To be eligible, all you must do is register for the meeting before 5 p.m. CDT Wednesday, April 24. The winner will be selected at random. This year’s meeting will be June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington D.C. Read more about the VAM contest, and more, in the latest SVS VAMail.

The Society for Vascular Surgery will provide complimentary meeting registration to a lucky attendee. To be eligible, all you must do is register for the meeting before 5 p.m. CDT Wednesday, April 24. The winner will be selected at random. This year’s meeting will be June 12 to 15 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington D.C. Read more about the VAM contest, and more, in the latest SVS VAMail.

GENEVA – The TRK inhibitor larotrectinib is highly active in lung cancer patients with NTRK gene fusions, supporting routine screening for such fusions in cases of lung cancer, according to investigators.

Will Pass/MDedge News

Although NTRK fusions are relatively infrequent in lung cancer, lead author Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, New York, suggested that their low frequency should not preclude testing in the current diagnostic setting.

“The frequency of TRK fusions in lung cancers in a prospective series that we put together was at the order of 0.23%, recognizing that the paradigm now for molecular profiling in lung cancer screens for many different drivers together, and not just single-gene testing,” Dr. Drilon said at the European Lung Cancer Conference. Dr. Drilon noted that larotrectinib is now approved by the Food and Drug Administration for the treatment of adult and pediatric patients with TRK fusion-positive cancers.

The present analysis involved 11 patients with metastatic lung adenocarcinoma and NTRK gene fusions from two previous clinical trials (NCT02122913 and NCT02576431); of these patients, 8 had NTRK1 fusions and 3 had NTRK3 fusions. Patients were given larotrectinib 100 mg twice daily on a continuous 28-day schedule until disease progression, unacceptable toxicity, or withdrawal. Almost all patients (10 out of 11) had a prior systemic therapy, and 5 patients had three or more prior therapies. The best response to previous therapies included four stable disease and one partial response. Out of 11 patients, 4 were ineligible for response analysis because of a treatment period of less than 1 month, leaving 7 evaluable patients; of these, 2 patients had stable disease, 4 had a partial response, and 1 had a complete response, translating to an overall response rate of 71%. On average, patients responded in just 1.8 months, with responses ranging from 7.4 months to 17.6 months, with the caveat that median duration of response has yet to be met. Treatment was generally well tolerated, with most adverse events being grade 1 or 2. Dr. Drilon cited a historical dose reduction rate of 9% and a discontinuation rate of less than 1% (out of 122 patients across cancer types).

Although most patients were heavily pretreated, Dr. Drilon highlighted one patient, a 76-year-old woman with non–small cell lung cancer, who had an NTRK1 gene fusion and multiple metastases to the brain and contralateral lung. This patient received larotrectinib as first-line therapy after refusing standard platinum doublet chemotherapy. The woman had a partial response, including “a near complete intracranial response with 95% volumetric shrinkage,” Dr. Drilon said at the meeting, presented by the European Society for Medical Oncology. “She remains on therapy as of six and a half months per the last data cutoff and is still doing well without any substantial toxicities from this drug.”

“In conclusion, larotrectinib is active in advanced lung cancers that harbor a TRK fusion,” Dr. Drilon said. “Of course, these [findings] underscore the utility of molecular profiling for TRK fusions when we look for drivers in patients with non–small cell lung cancer.”

When asked by the invited discussant if NTRK fusions should be tested up-front in all cases of non–small cell lung cancer, Dr. Drilon said, “I think the answer is absolutely yes.” He highlighted the fact that this study and other existing research has shown an overall response rate of about 70%, “which certainly beats the outcomes that we see with other systemic therapies, including, arguably, chemoimmunotherapy for this population. So I think that the paradigm here should be similar to the paradigm for EGFR and ALK, where we have an active target therapeutic that we can use up front, which would likely really improve outcomes for patients.”

Loxo Oncology Inc. and Bayer AG funded the study. The investigators reported financial relationships with Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, and others.

SOURCE: Drilon et al. ELCC 2019. Abstract 111O.

GENEVA – The TRK inhibitor larotrectinib is highly active in lung cancer patients with NTRK gene fusions, supporting routine screening for such fusions in cases of lung cancer, according to investigators.

Will Pass/MDedge News

Although NTRK fusions are relatively infrequent in lung cancer, lead author Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, New York, suggested that their low frequency should not preclude testing in the current diagnostic setting.

“The frequency of TRK fusions in lung cancers in a prospective series that we put together was at the order of 0.23%, recognizing that the paradigm now for molecular profiling in lung cancer screens for many different drivers together, and not just single-gene testing,” Dr. Drilon said at the European Lung Cancer Conference. Dr. Drilon noted that larotrectinib is now approved by the Food and Drug Administration for the treatment of adult and pediatric patients with TRK fusion-positive cancers.

The present analysis involved 11 patients with metastatic lung adenocarcinoma and NTRK gene fusions from two previous clinical trials (NCT02122913 and NCT02576431); of these patients, 8 had NTRK1 fusions and 3 had NTRK3 fusions. Patients were given larotrectinib 100 mg twice daily on a continuous 28-day schedule until disease progression, unacceptable toxicity, or withdrawal. Almost all patients (10 out of 11) had a prior systemic therapy, and 5 patients had three or more prior therapies. The best response to previous therapies included four stable disease and one partial response. Out of 11 patients, 4 were ineligible for response analysis because of a treatment period of less than 1 month, leaving 7 evaluable patients; of these, 2 patients had stable disease, 4 had a partial response, and 1 had a complete response, translating to an overall response rate of 71%. On average, patients responded in just 1.8 months, with responses ranging from 7.4 months to 17.6 months, with the caveat that median duration of response has yet to be met. Treatment was generally well tolerated, with most adverse events being grade 1 or 2. Dr. Drilon cited a historical dose reduction rate of 9% and a discontinuation rate of less than 1% (out of 122 patients across cancer types).

Although most patients were heavily pretreated, Dr. Drilon highlighted one patient, a 76-year-old woman with non–small cell lung cancer, who had an NTRK1 gene fusion and multiple metastases to the brain and contralateral lung. This patient received larotrectinib as first-line therapy after refusing standard platinum doublet chemotherapy. The woman had a partial response, including “a near complete intracranial response with 95% volumetric shrinkage,” Dr. Drilon said at the meeting, presented by the European Society for Medical Oncology. “She remains on therapy as of six and a half months per the last data cutoff and is still doing well without any substantial toxicities from this drug.”

“In conclusion, larotrectinib is active in advanced lung cancers that harbor a TRK fusion,” Dr. Drilon said. “Of course, these [findings] underscore the utility of molecular profiling for TRK fusions when we look for drivers in patients with non–small cell lung cancer.”

When asked by the invited discussant if NTRK fusions should be tested up-front in all cases of non–small cell lung cancer, Dr. Drilon said, “I think the answer is absolutely yes.” He highlighted the fact that this study and other existing research has shown an overall response rate of about 70%, “which certainly beats the outcomes that we see with other systemic therapies, including, arguably, chemoimmunotherapy for this population. So I think that the paradigm here should be similar to the paradigm for EGFR and ALK, where we have an active target therapeutic that we can use up front, which would likely really improve outcomes for patients.”

Loxo Oncology Inc. and Bayer AG funded the study. The investigators reported financial relationships with Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, and others.

SOURCE: Drilon et al. ELCC 2019. Abstract 111O.

GENEVA – The TRK inhibitor larotrectinib is highly active in lung cancer patients with NTRK gene fusions, supporting routine screening for such fusions in cases of lung cancer, according to investigators.

Will Pass/MDedge News

Although NTRK fusions are relatively infrequent in lung cancer, lead author Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, New York, suggested that their low frequency should not preclude testing in the current diagnostic setting.

“The frequency of TRK fusions in lung cancers in a prospective series that we put together was at the order of 0.23%, recognizing that the paradigm now for molecular profiling in lung cancer screens for many different drivers together, and not just single-gene testing,” Dr. Drilon said at the European Lung Cancer Conference. Dr. Drilon noted that larotrectinib is now approved by the Food and Drug Administration for the treatment of adult and pediatric patients with TRK fusion-positive cancers.

The present analysis involved 11 patients with metastatic lung adenocarcinoma and NTRK gene fusions from two previous clinical trials (NCT02122913 and NCT02576431); of these patients, 8 had NTRK1 fusions and 3 had NTRK3 fusions. Patients were given larotrectinib 100 mg twice daily on a continuous 28-day schedule until disease progression, unacceptable toxicity, or withdrawal. Almost all patients (10 out of 11) had a prior systemic therapy, and 5 patients had three or more prior therapies. The best response to previous therapies included four stable disease and one partial response. Out of 11 patients, 4 were ineligible for response analysis because of a treatment period of less than 1 month, leaving 7 evaluable patients; of these, 2 patients had stable disease, 4 had a partial response, and 1 had a complete response, translating to an overall response rate of 71%. On average, patients responded in just 1.8 months, with responses ranging from 7.4 months to 17.6 months, with the caveat that median duration of response has yet to be met. Treatment was generally well tolerated, with most adverse events being grade 1 or 2. Dr. Drilon cited a historical dose reduction rate of 9% and a discontinuation rate of less than 1% (out of 122 patients across cancer types).

Although most patients were heavily pretreated, Dr. Drilon highlighted one patient, a 76-year-old woman with non–small cell lung cancer, who had an NTRK1 gene fusion and multiple metastases to the brain and contralateral lung. This patient received larotrectinib as first-line therapy after refusing standard platinum doublet chemotherapy. The woman had a partial response, including “a near complete intracranial response with 95% volumetric shrinkage,” Dr. Drilon said at the meeting, presented by the European Society for Medical Oncology. “She remains on therapy as of six and a half months per the last data cutoff and is still doing well without any substantial toxicities from this drug.”

“In conclusion, larotrectinib is active in advanced lung cancers that harbor a TRK fusion,” Dr. Drilon said. “Of course, these [findings] underscore the utility of molecular profiling for TRK fusions when we look for drivers in patients with non–small cell lung cancer.”

When asked by the invited discussant if NTRK fusions should be tested up-front in all cases of non–small cell lung cancer, Dr. Drilon said, “I think the answer is absolutely yes.” He highlighted the fact that this study and other existing research has shown an overall response rate of about 70%, “which certainly beats the outcomes that we see with other systemic therapies, including, arguably, chemoimmunotherapy for this population. So I think that the paradigm here should be similar to the paradigm for EGFR and ALK, where we have an active target therapeutic that we can use up front, which would likely really improve outcomes for patients.”

Loxo Oncology Inc. and Bayer AG funded the study. The investigators reported financial relationships with Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, and others.

SOURCE: Drilon et al. ELCC 2019. Abstract 111O.

In a study that analyzed Twitter data from 5 American Headache Society (AHS) conferences held from 2014 to 2016 using their respective hashtags, AHS conference discussions featured a small group of accounts creating the bulk of the content, with individual medical professionals and host organizations generating the largest shares of tweets and mentions while host organizations and other individuals produced the most impressions. Researchers gathered data on numbers of tweets, impressions, participants, and mentions during a 10-day period surrounding each conference, as well as samples of Twitter accounts participating. They found:

• 19,936 tweets were generated across the 5 conferences.
• 58% of tweets were created by the top 10 participating accounts in each conference, which were primarily individual medical professionals and host organizations.
• 75% of impressions generated across the 5 conferences came from the top 10 participants in each.
• An average of 331 accounts participated in each conference.
• #migraine usage during conferences showed a significant increase from baseline in number of tweets.

Callister MN, Robbins MS, Callister NR, Vargas BB. Tweeting the headache meetings: Cross-sectional analysis of Twitter activity surrounding American Headache Society conferences. [Published online ahead of print March 20, 2019]. Headache. doi:10.1111/head.13500.

In a study that analyzed Twitter data from 5 American Headache Society (AHS) conferences held from 2014 to 2016 using their respective hashtags, AHS conference discussions featured a small group of accounts creating the bulk of the content, with individual medical professionals and host organizations generating the largest shares of tweets and mentions while host organizations and other individuals produced the most impressions. Researchers gathered data on numbers of tweets, impressions, participants, and mentions during a 10-day period surrounding each conference, as well as samples of Twitter accounts participating. They found:

• 19,936 tweets were generated across the 5 conferences.
• 58% of tweets were created by the top 10 participating accounts in each conference, which were primarily individual medical professionals and host organizations.
• 75% of impressions generated across the 5 conferences came from the top 10 participants in each.
• An average of 331 accounts participated in each conference.
• #migraine usage during conferences showed a significant increase from baseline in number of tweets.

Callister MN, Robbins MS, Callister NR, Vargas BB. Tweeting the headache meetings: Cross-sectional analysis of Twitter activity surrounding American Headache Society conferences. [Published online ahead of print March 20, 2019]. Headache. doi:10.1111/head.13500.

In a study that analyzed Twitter data from 5 American Headache Society (AHS) conferences held from 2014 to 2016 using their respective hashtags, AHS conference discussions featured a small group of accounts creating the bulk of the content, with individual medical professionals and host organizations generating the largest shares of tweets and mentions while host organizations and other individuals produced the most impressions. Researchers gathered data on numbers of tweets, impressions, participants, and mentions during a 10-day period surrounding each conference, as well as samples of Twitter accounts participating. They found:

• 19,936 tweets were generated across the 5 conferences.
• 58% of tweets were created by the top 10 participating accounts in each conference, which were primarily individual medical professionals and host organizations.
• 75% of impressions generated across the 5 conferences came from the top 10 participants in each.
• An average of 331 accounts participated in each conference.
• #migraine usage during conferences showed a significant increase from baseline in number of tweets.

Callister MN, Robbins MS, Callister NR, Vargas BB. Tweeting the headache meetings: Cross-sectional analysis of Twitter activity surrounding American Headache Society conferences. [Published online ahead of print March 20, 2019]. Headache. doi:10.1111/head.13500.

The Migraine Specific Quality-of-Life Questionnaire Version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain has sufficient reliability, validity, responsiveness, and appropriate interpretation standards for use in episodic migraine (EM) and chronic migraine (CM) clinical trials to assess the functional impact of migraine, a new study suggests. The 7-item MSQv2.1 ePRO RFR measures the functional impact of migraine on relationships with family and friends, leisure time, work or daily activities, productivity, concentration, tiredness, and energy. Measurement properties of the RFR were assessed using data from 2 EM (CGAG [n=851] and CGAH [n=909]) and 1 CM (CGAI [n=1090]) phase 3 clinical trial. Researchers found:

• Cronbach’s alpha values for internal consistency reliability were 0.93, 0.92, and 0.92 for CGAG, CGAH, and CGAI, respectively.
• Test-retest reliability intra-class correlation coefficients were 0.82 and 0.84 for CGAG and CGAH, and 0.85 for CGAI in stable patients.
• Convergent validity was supported by moderate to strong correlations between the RFR and both the Migraine Disability Assessment (MIDAS) and the Patient Global Impression of Severity (PGI-S).

Speck RM, Shalhoub H, Wyrwich KW, et al. Psychometric validation of the role function restrictive domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine. [Published online ahead of print March 12, 2019]. Headache. doi:10.1111/head.13497.

The Migraine Specific Quality-of-Life Questionnaire Version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain has sufficient reliability, validity, responsiveness, and appropriate interpretation standards for use in episodic migraine (EM) and chronic migraine (CM) clinical trials to assess the functional impact of migraine, a new study suggests. The 7-item MSQv2.1 ePRO RFR measures the functional impact of migraine on relationships with family and friends, leisure time, work or daily activities, productivity, concentration, tiredness, and energy. Measurement properties of the RFR were assessed using data from 2 EM (CGAG [n=851] and CGAH [n=909]) and 1 CM (CGAI [n=1090]) phase 3 clinical trial. Researchers found:

• Cronbach’s alpha values for internal consistency reliability were 0.93, 0.92, and 0.92 for CGAG, CGAH, and CGAI, respectively.
• Test-retest reliability intra-class correlation coefficients were 0.82 and 0.84 for CGAG and CGAH, and 0.85 for CGAI in stable patients.
• Convergent validity was supported by moderate to strong correlations between the RFR and both the Migraine Disability Assessment (MIDAS) and the Patient Global Impression of Severity (PGI-S).

Speck RM, Shalhoub H, Wyrwich KW, et al. Psychometric validation of the role function restrictive domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine. [Published online ahead of print March 12, 2019]. Headache. doi:10.1111/head.13497.

The Migraine Specific Quality-of-Life Questionnaire Version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain has sufficient reliability, validity, responsiveness, and appropriate interpretation standards for use in episodic migraine (EM) and chronic migraine (CM) clinical trials to assess the functional impact of migraine, a new study suggests. The 7-item MSQv2.1 ePRO RFR measures the functional impact of migraine on relationships with family and friends, leisure time, work or daily activities, productivity, concentration, tiredness, and energy. Measurement properties of the RFR were assessed using data from 2 EM (CGAG [n=851] and CGAH [n=909]) and 1 CM (CGAI [n=1090]) phase 3 clinical trial. Researchers found:

• Cronbach’s alpha values for internal consistency reliability were 0.93, 0.92, and 0.92 for CGAG, CGAH, and CGAI, respectively.
• Test-retest reliability intra-class correlation coefficients were 0.82 and 0.84 for CGAG and CGAH, and 0.85 for CGAI in stable patients.
• Convergent validity was supported by moderate to strong correlations between the RFR and both the Migraine Disability Assessment (MIDAS) and the Patient Global Impression of Severity (PGI-S).

Speck RM, Shalhoub H, Wyrwich KW, et al. Psychometric validation of the role function restrictive domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine. [Published online ahead of print March 12, 2019]. Headache. doi:10.1111/head.13497.

In a recent observational study, the loss of habituation and lower threshold for occipital cortex excitability were demonstrated electrophysiologically in patients with visual snow syndrome (VS). While statistically significant loss of habituation was seen in both VS patients with or without migraine in the right eye, statistically significant loss of habituation in the left eye and decreased threshold of left occipital cortex excitability was seen in patients who had VS with migraine. Researchers investigated the role of neurophysiological assessments of the occipital cortex in VS patients with (VS_m) or without migraine (VS_wom) and in healthy control (HC). They found:

• Twenty-nine volunteers were recruited for the study; the VS_m (n=10), the VS_wom (n=7), and the HC group (n=12) did not differ demographically.
• Flickering and floaters were reported in all VS patients and flickering in the dark was the most distressing symptomology in both VS groups.
• Higher visual analogue scale (VAS) scores for palinopsia, photophobia, and concentration difficulty were more frequent in VS_m patients.
• In the post hoc analysis, the VS patients did not differ according to the presence of migraine from right or left eye stimulations.

Yildiz FG, Turkyilmaz U, Unal-Cevik I. The clinical characteristics and neurophysiological assessments of the occipital cortex in visual snow syndrome with or without migraine. [Published online ahead of print March 8, 2019]. Headache. doi:10.1111/head.13494.

In a recent observational study, the loss of habituation and lower threshold for occipital cortex excitability were demonstrated electrophysiologically in patients with visual snow syndrome (VS). While statistically significant loss of habituation was seen in both VS patients with or without migraine in the right eye, statistically significant loss of habituation in the left eye and decreased threshold of left occipital cortex excitability was seen in patients who had VS with migraine. Researchers investigated the role of neurophysiological assessments of the occipital cortex in VS patients with (VS_m) or without migraine (VS_wom) and in healthy control (HC). They found:

• Twenty-nine volunteers were recruited for the study; the VS_m (n=10), the VS_wom (n=7), and the HC group (n=12) did not differ demographically.
• Flickering and floaters were reported in all VS patients and flickering in the dark was the most distressing symptomology in both VS groups.
• Higher visual analogue scale (VAS) scores for palinopsia, photophobia, and concentration difficulty were more frequent in VS_m patients.
• In the post hoc analysis, the VS patients did not differ according to the presence of migraine from right or left eye stimulations.

Yildiz FG, Turkyilmaz U, Unal-Cevik I. The clinical characteristics and neurophysiological assessments of the occipital cortex in visual snow syndrome with or without migraine. [Published online ahead of print March 8, 2019]. Headache. doi:10.1111/head.13494.

In a recent observational study, the loss of habituation and lower threshold for occipital cortex excitability were demonstrated electrophysiologically in patients with visual snow syndrome (VS). While statistically significant loss of habituation was seen in both VS patients with or without migraine in the right eye, statistically significant loss of habituation in the left eye and decreased threshold of left occipital cortex excitability was seen in patients who had VS with migraine. Researchers investigated the role of neurophysiological assessments of the occipital cortex in VS patients with (VS_m) or without migraine (VS_wom) and in healthy control (HC). They found:

• Twenty-nine volunteers were recruited for the study; the VS_m (n=10), the VS_wom (n=7), and the HC group (n=12) did not differ demographically.
• Flickering and floaters were reported in all VS patients and flickering in the dark was the most distressing symptomology in both VS groups.
• Higher visual analogue scale (VAS) scores for palinopsia, photophobia, and concentration difficulty were more frequent in VS_m patients.
• In the post hoc analysis, the VS patients did not differ according to the presence of migraine from right or left eye stimulations.

Yildiz FG, Turkyilmaz U, Unal-Cevik I. The clinical characteristics and neurophysiological assessments of the occipital cortex in visual snow syndrome with or without migraine. [Published online ahead of print March 8, 2019]. Headache. doi:10.1111/head.13494.