Susan London

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

Simply adding a default order to the electronic health record that automatically opts patients out of commonly used but unnecessary radiation oncology procedures can dramatically curtail their use, suggests a stepped-wedge, cluster-randomized, controlled trial.

Daily x-ray or CT imaging is often used to better reproducibly position patients during curative radiotherapy, but guidelines consider it unnecessary during palliative radiotherapy because of limited clinical benefit, according to the investigators, led by Sonam Sharma, MD, of the Icahn School of Medicine at Mount Sinai, New York, and the Abramson Cancer Center at the University of Pennsylvania, Philadelphia. “Unnecessary imaging can increase treatment time and expense for patients in distress,” they noted.

The investigators conducted a 2-year trial among 21 radiation oncologists from five practices (one university, four community) in which they added to the EHR a default order that specified no daily imaging during palliative radiation therapy. (Radiation oncologists could select another imaging frequency if they preferred.) The default order was first rolled out in the university practice and subsequently in the community practices.

Study analyses were based on 1,019 adult patients with bone, soft tissue, or brain metastases who received 1,188 courses of palliative three-dimensional conformal radiotherapy during the trial.

Results reported in a JAMA Oncology research letter showed that the proportion of patients receiving daily imaging during their palliative radiotherapy (imaging during 80% or more of treatments) fell from 68.2% during the combined preintervention periods to 32.4% during the combined intervention periods.

After potential confounders were taken into account, implementation of the default order in the EHR was associated with a more than halving of the odds of daily imaging during palliative radiotherapy (adjusted odds ratio, 0.37; P = .003), with an adjusted percentage point reduction of –18.8.

Findings were similar in the university practice alone (aOR, 0.33; P = .01; –22.3 percentage points) and in the community practices alone (aOR, 0.45; P = .02; –27.5 percentage points).

“In a network of five radiation oncology practices, introducing a default order in the EHR reduced unnecessary daily imaging during palliative radiotherapy,” Dr. Sharma and colleagues concluded. “Our findings suggest that simple nudges, such as setting default orders, can meaningfully reduce unnecessary care.”

Dr. Sharma reported that she had no relevant conflicts of interest. The study was funded in part by the National Cancer Institute and the University of Pennsylvania Health System through the Penn Medicine Nudge Unit and the department of radiation oncology.

SOURCE: Sharma S et al. JAMA Oncol. 2019 Jun 27. doi: 10.1001/jamaoncol.2019.1432.

The safety profile of combination abiraterone acetate (Zytiga) and glucocorticoid therapy in men with metastatic castration-resistant prostate cancer (mCRPC) hinged on the specific steroid regimen, according to a phase 2 open-label randomized controlled trial.

alexdans/Thinkstock

Glucocorticoids are added to abiraterone in part to prevent mineralocorticoid excess, but can also have adverse effects of their own, noted lead investigator Gerhardt Attard, MD, of the University College London Cancer Institute, London, and colleagues. Understanding of the comparative physiologic effects of various regimens is limited.

In the trial, the investigators randomized 164 men with mCRPC from 22 centers in 5 countries (median age 70 years) to 4 glucocorticoid regimens, each combined with abiraterone acetate, 1,000 mg, daily: prednisone, 5 mg, twice daily; prednisone, 5 mg, once daily; prednisone, 2.5 mg, twice daily; and dexamethasone, 0.5 mg, once daily.

Results reported in JAMA Oncology showed that the proportion of patients who had not developed toxicity (hypotension or hypokalemia) from mineralocorticoid excess during the first 24 weeks of treatment was highest, at about 70%, with prednisone, 5 mg, twice daily, and with dexamethasone, and only these regimens had confidence intervals excluding occurrence of this toxicity in at least half of patients. However, patients in the dexamethasone group had significantly heightened risks of insulin resistance and bone mineral density loss at the end of follow-up.

The median radiographic progression-free survival was 18.5 months in the group given prednisone, 5 mg, twice daily; 15.3 months in the group given prednisone, 5 mg, once daily; 12.8 months in the group given prednisone, 2.5 mg, twice daily; and 26.6 months in the group given dexamethasone, 0.5 mg, once daily.

“Different glucocorticoid regimens make distinct compromises on control of mineralocorticoid excess, changes in body composition, and development of insulin resistance,” Dr. Attard and coinvestigators summarized. “This trial provides results consistent with the approved use of abiraterone acetate with prednisone, 5 mg, twice daily for the treatment of mCRPC. Long-term adverse metabolic and musculoskeletal changes are small and do not appear to have a detrimental effect on patient-reported quality of life.”

At the same time, lower-dose prednisone regimens – with their more modest long-term risks of insulin resistance, increased body fat, and bone mineral density loss – can still be used, with caution. “With careful monitoring, the risk of hypokalemia with lower glucocorticoid doses can be mitigated, as demonstrated in the LATITUDE and STAMPEDE trials where no major safety concerns were raised,” they elaborated.

Dr. Attard disclosed personal fees, research support, and travel support from Janssen during the conduct of the study; as well as personal fees research, and/or travel support from numerous other pharmaceutical companies. The study was funded by Janssen EMEA.

SOURCE: Attard G et al. JAMA Oncol. Published online June 27, 2019. doi:10.1001/jamaoncol.2019.1011.

The safety profile of combination abiraterone acetate (Zytiga) and glucocorticoid therapy in men with metastatic castration-resistant prostate cancer (mCRPC) hinged on the specific steroid regimen, according to a phase 2 open-label randomized controlled trial.

alexdans/Thinkstock

Glucocorticoids are added to abiraterone in part to prevent mineralocorticoid excess, but can also have adverse effects of their own, noted lead investigator Gerhardt Attard, MD, of the University College London Cancer Institute, London, and colleagues. Understanding of the comparative physiologic effects of various regimens is limited.

In the trial, the investigators randomized 164 men with mCRPC from 22 centers in 5 countries (median age 70 years) to 4 glucocorticoid regimens, each combined with abiraterone acetate, 1,000 mg, daily: prednisone, 5 mg, twice daily; prednisone, 5 mg, once daily; prednisone, 2.5 mg, twice daily; and dexamethasone, 0.5 mg, once daily.

Results reported in JAMA Oncology showed that the proportion of patients who had not developed toxicity (hypotension or hypokalemia) from mineralocorticoid excess during the first 24 weeks of treatment was highest, at about 70%, with prednisone, 5 mg, twice daily, and with dexamethasone, and only these regimens had confidence intervals excluding occurrence of this toxicity in at least half of patients. However, patients in the dexamethasone group had significantly heightened risks of insulin resistance and bone mineral density loss at the end of follow-up.

The median radiographic progression-free survival was 18.5 months in the group given prednisone, 5 mg, twice daily; 15.3 months in the group given prednisone, 5 mg, once daily; 12.8 months in the group given prednisone, 2.5 mg, twice daily; and 26.6 months in the group given dexamethasone, 0.5 mg, once daily.

“Different glucocorticoid regimens make distinct compromises on control of mineralocorticoid excess, changes in body composition, and development of insulin resistance,” Dr. Attard and coinvestigators summarized. “This trial provides results consistent with the approved use of abiraterone acetate with prednisone, 5 mg, twice daily for the treatment of mCRPC. Long-term adverse metabolic and musculoskeletal changes are small and do not appear to have a detrimental effect on patient-reported quality of life.”

At the same time, lower-dose prednisone regimens – with their more modest long-term risks of insulin resistance, increased body fat, and bone mineral density loss – can still be used, with caution. “With careful monitoring, the risk of hypokalemia with lower glucocorticoid doses can be mitigated, as demonstrated in the LATITUDE and STAMPEDE trials where no major safety concerns were raised,” they elaborated.

Dr. Attard disclosed personal fees, research support, and travel support from Janssen during the conduct of the study; as well as personal fees research, and/or travel support from numerous other pharmaceutical companies. The study was funded by Janssen EMEA.

SOURCE: Attard G et al. JAMA Oncol. Published online June 27, 2019. doi:10.1001/jamaoncol.2019.1011.

The safety profile of combination abiraterone acetate (Zytiga) and glucocorticoid therapy in men with metastatic castration-resistant prostate cancer (mCRPC) hinged on the specific steroid regimen, according to a phase 2 open-label randomized controlled trial.

alexdans/Thinkstock

Glucocorticoids are added to abiraterone in part to prevent mineralocorticoid excess, but can also have adverse effects of their own, noted lead investigator Gerhardt Attard, MD, of the University College London Cancer Institute, London, and colleagues. Understanding of the comparative physiologic effects of various regimens is limited.

In the trial, the investigators randomized 164 men with mCRPC from 22 centers in 5 countries (median age 70 years) to 4 glucocorticoid regimens, each combined with abiraterone acetate, 1,000 mg, daily: prednisone, 5 mg, twice daily; prednisone, 5 mg, once daily; prednisone, 2.5 mg, twice daily; and dexamethasone, 0.5 mg, once daily.

Results reported in JAMA Oncology showed that the proportion of patients who had not developed toxicity (hypotension or hypokalemia) from mineralocorticoid excess during the first 24 weeks of treatment was highest, at about 70%, with prednisone, 5 mg, twice daily, and with dexamethasone, and only these regimens had confidence intervals excluding occurrence of this toxicity in at least half of patients. However, patients in the dexamethasone group had significantly heightened risks of insulin resistance and bone mineral density loss at the end of follow-up.

The median radiographic progression-free survival was 18.5 months in the group given prednisone, 5 mg, twice daily; 15.3 months in the group given prednisone, 5 mg, once daily; 12.8 months in the group given prednisone, 2.5 mg, twice daily; and 26.6 months in the group given dexamethasone, 0.5 mg, once daily.

“Different glucocorticoid regimens make distinct compromises on control of mineralocorticoid excess, changes in body composition, and development of insulin resistance,” Dr. Attard and coinvestigators summarized. “This trial provides results consistent with the approved use of abiraterone acetate with prednisone, 5 mg, twice daily for the treatment of mCRPC. Long-term adverse metabolic and musculoskeletal changes are small and do not appear to have a detrimental effect on patient-reported quality of life.”

At the same time, lower-dose prednisone regimens – with their more modest long-term risks of insulin resistance, increased body fat, and bone mineral density loss – can still be used, with caution. “With careful monitoring, the risk of hypokalemia with lower glucocorticoid doses can be mitigated, as demonstrated in the LATITUDE and STAMPEDE trials where no major safety concerns were raised,” they elaborated.

Dr. Attard disclosed personal fees, research support, and travel support from Janssen during the conduct of the study; as well as personal fees research, and/or travel support from numerous other pharmaceutical companies. The study was funded by Janssen EMEA.

SOURCE: Attard G et al. JAMA Oncol. Published online June 27, 2019. doi:10.1001/jamaoncol.2019.1011.

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.

Two liquid biopsy assays show generally good concordance with the gold standard of next-generation sequencing (NGS) performed on tissue for detecting epidermal growth factor receptor (EGFR) mutations in non–small cell lung (NSCLC), finds a retrospective cohort study.

Availability of targeted therapies for EGFR-mutated NSCLC underscores the importance of detecting these molecular aberrations, note lead investigator Christi M.J. Steendam, MD, department of pulmonary diseases, Erasmus MC Rotterdam, and Amphia Hospital, Breda, the Netherlands, and coinvestigators. In addition, assessing and monitoring mutational status can provide information about resistance and better inform treatment decisions.

The investigators studied 36 patients with EGFR-mutated NSCLC who had experienced progression on their current therapy and had both tissue and plasma available. They first compared results of droplet digital polymerase chain reaction (ddPCR) and NGS for detecting primary activating EGFR mutations and the resistance p.T790M EGFR mutation (the most common resistance mechanism to first- and second-generation tyrosine kinase inhibitors in this population) in plasma-derived cell-free DNA. They then compared each assay against NGS performed on conventional tissue.

Study results showed high agreement between ddPCR and NGS, at 86% for detection of the primary activating mutation and at 94% for detection of the p.T790M mutation. Findings were similar for the quantified allele ratio (mutant alleles divided by total alleles).

Overall, 15 patients (41.7%) had some degree of discrepant results. Six had no detectable mutations in cell-free DNA, three had detectable p.T790M in plasma but not in tissue, and three others had detectable p.T790M in tissue but not in plasma.

Finally, there was generally good concordance of the cell-free DNA results and the results obtained in tissue for detection of the primary activating mutation (69% for ddPCR, 83% for NGS) and for detection of p.T790M (75% for ddPCR, 75% for NGS). Patients with discordant results tended to have intrathoracic and/or CNS progression.

“ddPCR and NGS yield comparable results, with similar sensitivity for the mutations that can be detected by both methods, and the concordance with tissue-based results is high,” Dr. Steendam and coinvestigators summarize in JCO Precision Oncology. “When searching for a resistance mechanism, NGS analysis of cell-free DNA in plasma offers a more comprehensive view than ddPCR, with comparable precision at a single mutation level. When no mutations are detected in plasma, tissue-based investigation remains desirable.”

“Our results confirm the ability to detect targetable aberrations in blood, which provides possibilities for new lines of targeted treatments in daily practice without the necessity of tissue procurement in many patients,” they conclude.

Dr. Steendam disclosed that she receives research funding from AstraZeneca (institutional) and travel, accommodations, and/or expenses from Roche, Boehringer Ingelheim, and Eli Lilly. The study did not receive any specific funding.

SOURCE: Steendam CMJ et al. JCO Precis Oncol. 2019 June 20. doi: 10.1200/PO.18.00401.

Giving steroids for indications other than cancer palliation doesn’t compromise the effectiveness of immunotherapy for advanced non–small cell lung cancer (NSCLC), suggests a single-center retrospective cohort study.

The immunosuppressant activity of corticosteroids and recent reports linking them to poorer outcomes has raised concern about their use during immunotherapy, noted Biagio Ricciuti, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. But mechanisms underpinning this association are unclear.

The investigators studied 650 patients with NSCLC treated with immunotherapy targeting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), either as monotherapy or with other immunotherapy. Overall, 14.3% were receiving 10 mg or more of prednisone daily when they started the immunotherapy, a cutoff selected for study because it has been used an exclusion criterion for clinical trials.

Results reported in the Journal of Clinical Oncology showed that, compared with other patients, those who received 10 mg or more of steroids indeed had poorer median progression-free survival (2.0 vs. 3.4 months; P = .01) and overall survival (4.9 vs. 11.2 months; P less than .001).

However, when the indication for steroid therapy was considered, median progression-free survival was just 1.4 months among patients who received 10 mg or more prednisone for cancer-related palliation, compared with 4.6 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons (for example, autoimmune disease, chronic obstructive pulmonary disease flare, hypersensitivity prophylaxis, or management of noncancer pain) and 3.4 months among patients who received 0-10 mg of prednisone (P less than .001 across groups).

Similarly, median overall survival was just 2.2 months among patients who received 10 mg or more prednisone for palliative indications, but 10.7 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons and 11.2 months among patients who received less than 10 mg prednisone (P less than .001 across groups).

In a multivariate analysis that adjusted for performance status and PD-L1 positivity and that used patients receiving up to 10 mg prednisone as the comparator, patients receiving 10 mg or more for cancer palliation had a trend toward high risk of progression-free survival events and a higher risk of death (hazard ratio, 1.40; P less than .06 and HR, 1.60; P = .02, respectively). In contrast, patients receiving 10 mg or more for cancer-unrelated reasons did not have elevated risks (HR, 0.62; P = .14 and HR, 0.91; P = .79, respectively).

“These data suggest that the significantly worse outcomes among patients who receive corticosteroids before immunotherapy are driven by the group of patients treated with corticosteroids for palliative oncologic symptom management, rather than by patients receiving corticosteroids for other reasons,” Dr. Ricciuti and coinvestigators wrote. “Corticosteroid use for cancer symptom management might simply correlate with patients who have adverse prognostic factors (e.g., brain metastases and poor performance status) rather than cause a clinically significant blunting of the response to [immune checkpoint inhibitors].

“Our data suggest that corticosteroids should not necessarily be decreased or discontinued before the start of immunotherapy out of a theoretical concern that corticosteroids could impair a response to immunotherapy,” the investigators concluded. “Additional mechanistic studies are needed to identify whether the use of corticosteroids affects specific aspects of the immune system necessary for immunotherapy activity.”

Dr. Ricciuti reported that he has no relevant conflicts of interest. The study did not receive any funding.

SOURCE: Ricciuti B et al. J Clin Oncol. 2019 Jun 17. doi: 10.1200/JCO.19.00189.

Giving steroids for indications other than cancer palliation doesn’t compromise the effectiveness of immunotherapy for advanced non–small cell lung cancer (NSCLC), suggests a single-center retrospective cohort study.

The immunosuppressant activity of corticosteroids and recent reports linking them to poorer outcomes has raised concern about their use during immunotherapy, noted Biagio Ricciuti, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. But mechanisms underpinning this association are unclear.

The investigators studied 650 patients with NSCLC treated with immunotherapy targeting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), either as monotherapy or with other immunotherapy. Overall, 14.3% were receiving 10 mg or more of prednisone daily when they started the immunotherapy, a cutoff selected for study because it has been used an exclusion criterion for clinical trials.

Results reported in the Journal of Clinical Oncology showed that, compared with other patients, those who received 10 mg or more of steroids indeed had poorer median progression-free survival (2.0 vs. 3.4 months; P = .01) and overall survival (4.9 vs. 11.2 months; P less than .001).

However, when the indication for steroid therapy was considered, median progression-free survival was just 1.4 months among patients who received 10 mg or more prednisone for cancer-related palliation, compared with 4.6 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons (for example, autoimmune disease, chronic obstructive pulmonary disease flare, hypersensitivity prophylaxis, or management of noncancer pain) and 3.4 months among patients who received 0-10 mg of prednisone (P less than .001 across groups).

Similarly, median overall survival was just 2.2 months among patients who received 10 mg or more prednisone for palliative indications, but 10.7 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons and 11.2 months among patients who received less than 10 mg prednisone (P less than .001 across groups).

In a multivariate analysis that adjusted for performance status and PD-L1 positivity and that used patients receiving up to 10 mg prednisone as the comparator, patients receiving 10 mg or more for cancer palliation had a trend toward high risk of progression-free survival events and a higher risk of death (hazard ratio, 1.40; P less than .06 and HR, 1.60; P = .02, respectively). In contrast, patients receiving 10 mg or more for cancer-unrelated reasons did not have elevated risks (HR, 0.62; P = .14 and HR, 0.91; P = .79, respectively).

“These data suggest that the significantly worse outcomes among patients who receive corticosteroids before immunotherapy are driven by the group of patients treated with corticosteroids for palliative oncologic symptom management, rather than by patients receiving corticosteroids for other reasons,” Dr. Ricciuti and coinvestigators wrote. “Corticosteroid use for cancer symptom management might simply correlate with patients who have adverse prognostic factors (e.g., brain metastases and poor performance status) rather than cause a clinically significant blunting of the response to [immune checkpoint inhibitors].

“Our data suggest that corticosteroids should not necessarily be decreased or discontinued before the start of immunotherapy out of a theoretical concern that corticosteroids could impair a response to immunotherapy,” the investigators concluded. “Additional mechanistic studies are needed to identify whether the use of corticosteroids affects specific aspects of the immune system necessary for immunotherapy activity.”

Dr. Ricciuti reported that he has no relevant conflicts of interest. The study did not receive any funding.

SOURCE: Ricciuti B et al. J Clin Oncol. 2019 Jun 17. doi: 10.1200/JCO.19.00189.

Giving steroids for indications other than cancer palliation doesn’t compromise the effectiveness of immunotherapy for advanced non–small cell lung cancer (NSCLC), suggests a single-center retrospective cohort study.

The immunosuppressant activity of corticosteroids and recent reports linking them to poorer outcomes has raised concern about their use during immunotherapy, noted Biagio Ricciuti, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. But mechanisms underpinning this association are unclear.

The investigators studied 650 patients with NSCLC treated with immunotherapy targeting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1), either as monotherapy or with other immunotherapy. Overall, 14.3% were receiving 10 mg or more of prednisone daily when they started the immunotherapy, a cutoff selected for study because it has been used an exclusion criterion for clinical trials.

Results reported in the Journal of Clinical Oncology showed that, compared with other patients, those who received 10 mg or more of steroids indeed had poorer median progression-free survival (2.0 vs. 3.4 months; P = .01) and overall survival (4.9 vs. 11.2 months; P less than .001).

However, when the indication for steroid therapy was considered, median progression-free survival was just 1.4 months among patients who received 10 mg or more prednisone for cancer-related palliation, compared with 4.6 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons (for example, autoimmune disease, chronic obstructive pulmonary disease flare, hypersensitivity prophylaxis, or management of noncancer pain) and 3.4 months among patients who received 0-10 mg of prednisone (P less than .001 across groups).

Similarly, median overall survival was just 2.2 months among patients who received 10 mg or more prednisone for palliative indications, but 10.7 months among patients who received 10 mg or more prednisone for cancer-unrelated reasons and 11.2 months among patients who received less than 10 mg prednisone (P less than .001 across groups).

In a multivariate analysis that adjusted for performance status and PD-L1 positivity and that used patients receiving up to 10 mg prednisone as the comparator, patients receiving 10 mg or more for cancer palliation had a trend toward high risk of progression-free survival events and a higher risk of death (hazard ratio, 1.40; P less than .06 and HR, 1.60; P = .02, respectively). In contrast, patients receiving 10 mg or more for cancer-unrelated reasons did not have elevated risks (HR, 0.62; P = .14 and HR, 0.91; P = .79, respectively).

“These data suggest that the significantly worse outcomes among patients who receive corticosteroids before immunotherapy are driven by the group of patients treated with corticosteroids for palliative oncologic symptom management, rather than by patients receiving corticosteroids for other reasons,” Dr. Ricciuti and coinvestigators wrote. “Corticosteroid use for cancer symptom management might simply correlate with patients who have adverse prognostic factors (e.g., brain metastases and poor performance status) rather than cause a clinically significant blunting of the response to [immune checkpoint inhibitors].

“Our data suggest that corticosteroids should not necessarily be decreased or discontinued before the start of immunotherapy out of a theoretical concern that corticosteroids could impair a response to immunotherapy,” the investigators concluded. “Additional mechanistic studies are needed to identify whether the use of corticosteroids affects specific aspects of the immune system necessary for immunotherapy activity.”

Dr. Ricciuti reported that he has no relevant conflicts of interest. The study did not receive any funding.

SOURCE: Ricciuti B et al. J Clin Oncol. 2019 Jun 17. doi: 10.1200/JCO.19.00189.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

Implementation of low-dose CT screening for lung cancer in community settings is successfully detecting the disease at an early, more treatable stage, suggests a survey of U.S. lung cancer screening centers.

Such screening led to a 20% reduction in lung cancer mortality in the National Lung Screening Trial (N Engl J Med. 2011;365:395-409), prompting the Centers for Medicare & Medicaid Services to start covering it in 2015. However, fewer than a third of trial practices were community based, and questions lingered regarding applicability of this screening in nonacademic settings.

Investigators working under senior author Jennifer C. King, PhD, senior director of science and research at the GO2 Foundation for Lung Cancer, Washington, administered a 21-question survey to 165 lung cancer screening centers designated as Screening Centers of Excellence asking about their 2016 program data and practices. Overall, 62% of the centers were community based, having no university or other academic affiliation.

Results reported in the Journal of Oncology Practice showed that more than half of 529 lung cancer diagnoses the centers made in 2016 were made at stage I or limited stage, with the same pattern seen for community and academic centers. Findings were similar when analyses instead considered Lung Imaging Reporting and Data System results for 40,000 low-dose CT scans performed that year.

Community and academic centers differed in how they addressed the CMS requirement for a prescreening shared decision making visit led by a health practitioner, with the former more commonly relying on only primary care providers (52% vs. 40%). The centers were similar in how they addressed the CMS requirement for smoking cessation services, with both using referral to a quitline, cessation counseling within the screening facility, and printed educational materials; however, academic centers more commonly followed up with current smokers (52% vs. 36%).

The main barriers to implementing screening were insurance and billing issues, lack of provider referral, lack of patient awareness, and internal work flow challenges, cited by more than half of centers overall. Community centers less often cited staffing and time limitations (35% vs. 53%) and insurance and billing issues (64% vs. 74%), but percentages were similar for other barriers.

“There has been concern about the ability of nonacademic centers to implement lung cancer screening as safely and effectively as academic medical centers,” Dr. King and coauthors wrote. “In this study, we not only demonstrate that lung cancer screening is happening in the community setting, but also that nonacademic screening programs are using similar protocols and are seeing similar findings as academic medical centers.

“These data indicate that responsible implementation is possible in the community and results in a meaningful stage shift for lung cancer diagnoses, and providers should support ongoing implementation of lung cancer screening efforts,” they concluded.

Dr. King reported that she receives honoraria from MedImmune, AstraZeneca, and Genentech; has a consulting or advisory role with GRAIL, Tesaro, AbbVie, and Foundation Medicine; and receives research funding from AstraZeneca. The study was supported by the GO2 Foundation for Lung Cancer.

SOURCE: King JC et al. J Oncol Pract. 2019 May 31. doi: 10.1200/JOP.18.00788.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.