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Patients With Stage I NSCLC Who Are Not Treated with Either Surgical Resection or Radiation Therapy
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Purpose: Approximately 10% of patients with stage I non-small cell lung cancer (NSCLC) are managed without definitive therapy. We therefore investigated whether this rate is similar among veterans cared for by the Veterans Health Administration (VHA), and explored the outcomes and factors associated with under- utilization of these standard of care management strategies.
Methods: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) was queried for all patients diagnosed with NSCLC between 2003 and 2016. Receipt of definitive therapy was determined using VHA cancer registry data, CPT codes and ICD-9/ICD-10 procedure codes within a year after diagnosis. We also captured receipt of chemotherapy as the primary course of treatment, whenever this was the case. Vital status data were assessed using the Kaplan-Meier method.
Results: A total of 19,971 veterans were diagnosed with biopsy-proven clinical stage I NSCLC. The primary treatment for 13,080 (65.5%), 4,889 (24.5%), and 2,002 (10.0%) patients was surgery, RT, or no documented surgery or RT, respectively. The 5-year overall survival for these 3 groups was 53.1%, 19.7%, and 8.9%, respectively. The proportion of patients without documentation of definitive therapy was highest in 2004 at 16.9%, decreasing to 6.3% by 2016. Patients treated at a VA medical center with an on-site radiation oncology service were more likely to receive definitive therapy (chi-square P<0.01). However, this difference was driven by higher utilization of surgery instead of radiation therapy. Among patients without documentation of definitive therapy, 17.4% received systemic chemotherapy as their first reported treatment course.
Conclusion: The proportion of patients without documentation of definitive surgery or RT was similar to previous publications. The rate of no definitive therapy has declined by more than 50% over the past decade, and is coincident with the increased availability of onsite radiotherapy services, as well as minimally invasive thoracic surgery and stereotactic radiotherapy within and outside the VHA. Future investigations of this dataset are likely to increase our understanding about the reasons for treatment delay or avoidance, and its consequences for patients with a highly curable stage I NSCLC.
Low-Dose Screening CT for Lung Cancer in Selected High-Risk Veterans with a Significant Smoking History: The Providence VA’s Experience
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
Background: In the US, Lung cancer is the second most common malignancy, but the most common cause of cancer deaths. In 2010, the National Lung Screening Trial described a 20.3% reduction in lung cancer mortality in high-risk patients screened by low-dose spiral CT (LDCT). In 2012, multiple groups established screening guidelines. The National Comprehensive Cancer Network recommended yearly screening for patients aged 55 to 75 years, ≥30 packyears of smoking, or smoking cessation within 15 years. In late 2013, LDCT screening for lung cancer was initiated at the Providence VA Medical Center. It was anticipated that over time there would be a rise in early stage cancers and decrease in late stage cancers. We submitted preliminary data at AVAHO in 2015 with increased earlier detection as anticipated. We have now completed 5 years of screening and are presenting data from 2014 through 2018.
Results: The number of screening CTs has increased almost every year (1929, 1875, 1916, 2201, 2336 respectively), and the number with cancer decreased from 1.34% (2014) to 0.008% (2018). The majority of NSCLCs found have been early stage, but with Small Cell Lung Cancer, 50% had limited and 50% extensive disease. Yearly screening is not likely to increase early detection of Small Cell Lung Cancer. Percentages of stage I & II for NSCLC prior to screening were 30% and 27% in 2012 and 2013 respectively. In 2014 – 2018 percentages were 69%, 60%, 50%, 83% and 50%. In 2016 and 2018, several veterans came to the VA to establish care with a known nodule, or had their first screening CT here, and they were found to have late stage disease. When we subtracted those first time screens the percentages of stage I & II were 69%, 60%, 78%, 83%, and 56%.
Discussion: As expected, for NSCLC yearly LDCT screening increased “pickup” of early stage disease. Unanswered questions include: How long should annual screening continue; What is the financial, emotional and radiation exposure impact of frequent screening, especially for those who need to be followed at more frequent intervals.
HER2-mutant NSCLC confers high brain metastases risk
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
The report by Offin et al. adds to the growing body of literature supporting the potential value of surveillance brain imaging in a subset of patients with lung cancer. The optimal frequency of surveillance brain imaging in patients with non–small cell lung cancer (NSCLC) after the initial diagnosis of metastatic disease has not been established, and practices vary widely. For example, in our own practice, we routinely perform surveillance brain imaging for patients with ALK fusion–positive lung cancer even in the absence of new neurologic symptoms or signs because of a relatively high cumulative incidence of brain metastases within this subgroup in retrospective studies. Whether a similar approach should be taken for HER2-mutant patients awaits further data. Ultimately, in this era of rapidly evolving therapies for advanced NSCLC, early detection of relatively small, asymptomatic brain metastases could translate into the ability to avoid potentially morbid local CNS-directed therapies (such as surgical resection or whole-brain radiotherapy) while allowing the prompt initiation of CNS-active systemic therapies. At the same time, surveillance strategies will need to be data driven and balanced against health utilization considerations and patient preferences.
Overall, the study by Offin et al. offers important new insights into the incidence of brain metastases in HER2-mutant NSCLC. The finding of a relatively high cumulative incidence of brain metastases in this patient population and the shorter survival resulting therein underscore the urgency of developing better HER2-targeted therapeutics with CNS efficacy. Finally, further investigation will be needed to continue to elucidate potential differences in the CNS tropism of distinct oncogenic drivers in NSCLC and to understand the biological mechanisms underlying these differences.
Remarks by Jessica J. Lin, MD, and Justin F. Gainor, MD, from the Massachusetts General Hospital Cancer Center in Boston are adapted and condensed from an editorial accompanying the study by Offin et al. published online in Cancer. No funding source was reported. Dr. Lin reported serving as a compensated consultant for or receiving honoraria from Chugai and Boehringer Ingelheim, and receiving institutional research funding from Loxo Oncology and Novartis. Dr. Gainor has served as a compensated consultant for or received honoraria or research support from numerous pharmaceutical companies and has an immediate family member who is an employee of Ironwood Pharmaceuticals.
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
Although only a small percentage of non–small cell lung cancers are positive for HER2 mutations, HER2-mutant lung cancers are associated with a high incidence of brain metastases, investigators have found.
Among 98 consecutive patients with HER2-mutant non–small cell lung cancer (NSCLC), the incidence of brain metastases at initial diagnosis was comparable with or slightly lower than that seen with other, more common mutations, but the incidence during treatment was significantly higher than in patients with KRAS-mutant NSCLC, and trended higher than the incidence rate of brain metastases in patients with epidermal growth factor receptor (EGFR)–mutated NSCLC, reported Michael Offin, MD, and colleagues from Memorial Sloan Kettering Cancer in New York.
“This finding provides a framework for CNS surveillance and treatment strategies, including radiotherapy, for patients with HER2-mutant lung cancers and underlines the urgent need for the development of novel HER2-targeted agents with activity in the CNS,” they wrote in Cancer.
NSCLC with oncogenic driver mutations in HER2 account for 2% of adenocarcinomas of the lung, but relatively little is known about the risk for brain metastases in patients HER2-mutant lung cancer, the authors wrote.
“Because HER2-amplified breast cancers are more likely to develop brain metastases through constitutive HER2 signaling, we hypothesize that HER2-mutant lung cancers are also more apt to develop brain metastases in comparison with lung cancers driven by other oncogenes,” they wrote.
To explore this hypothesis, they conducted a retrospective record review of 98 patients treated at their center with metastatic HER2-mutant NSCLC, and compared them with 200 patients with metastatic KRAS-mutant NSCLC, and 200 with metastatic, sensitizing EGFR-mutant NSCLC.
They found that at the initial diagnosis of metastatic disease, the percentage of patients with brain metastases was similar between patients with HER2 mutations and those with KRAS mutations (19% vs. 24%; odds ratio for HER2 vs. KRAS, 0.7; P = .33). However significantly more patients with EGFR-mutant tumors had brain metastases at diagnosis, compared with patients HER2 mutations (31% vs. 19%; OR, 0.5; P = .03).
Interestingly, significantly more patients with HER2-mutant tumors developed brain metastases on treatment than patients with KRAS-mutant tumors (28% vs. 8%; hazard ratio, 5.2; P less than .001). There was also a trend toward more on-treatment brain metastases among patients with HER2 mutations, compared with patients with EGFR mutation (28% vs .16%; HR, 1.7), but this difference was not statistically significant.
The risk for on-treatment brain metastases was even higher among patients with a HER2 mutation characterized by a 12 base–pair, in-frame insertion in exon 20 (HER2 YVMA). In these patients, the OR for brain metastases developing during treatment versus patients with KRAS mutations was 5.9 (P less than .001).
The median overall survival was worse for patients with KRAS-mutant NSCLC (1.1 years) and HER2-mutant cancers (1.6 years) versus 3 years for patients with EFGR-mutant cancers (P less than .001 for KRAS; P = .002 for HER2 vs. EGFR).
The use of HER2-targeted therapies did not have an effect on either the development of brain metastases or survival, and overall survival was slightly but significantly worse for patients with HER2-mutant tumors who had radiotherapy of the brain.
The study was supported by the National Institutes of Health through a National Cancer Institute Cancer Center support grant and by the Eloise Briskin Foundation. Dr. Offin reported honoraria from Bristol-Myers Squibb, Merck, PharmaMar, Novartis, and Targeted Oncology. Multiple coauthors had similar disclosures.
SOURCE: Offin M et al. Cancer. 2019 Aug 30. doi: 10.1002/cncr.32461.
FROM CANCER
Durvalumab-Induced Hyperprogressive Disease in Non-Metastatic Lung Cancer
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation: A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
Cardiac Tamponade in a Patient with Stage IV Lung Adenocarcinoma Treated with Pembrolizumab
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.
Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.
Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.
Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.
Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.
Use of Palliative Radiotherapy for Stage IV Lung Cancer Patients with Thoracic Symptoms in the Veterans Health Administration (VHA)
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”
Background: Palliative radiotherapy plays an important role in metastatic lung cancer (LC) treatment. Of VHA LC patients, 46% present with metastatic disease. The American Society for Radiation Oncology (ASTRO) has developed evidenced-based guidelines regarding management of metastatic LC.
Methods: In May 2016, an electronic survey of 84 VHA Radiation Oncologists (ROs) was conducted to assess metastatic LC management. Information on years in practice, employment status, academic appointment, board certification, and familiarity with ASTRO lung cancer guidelines was obtained. Two clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/ against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or YAG laser technology. Survey results were assessed for concordance with ASTRO guidelines.
Results: The survey response rate was 64%. Among respondents, 96% were board certified, 90% held academic appointments, 85% were full-time employees, 11% were part-time employees, and 3% were employed on contract. When asked about use of palliative radiotherapy for lung cancer, 88% were familiar with ASTRO guidelines, 13% had used Stereotactic Body Radiotherapy (SBRT) for palliation, and 26% referred to outside centers for EBB.
Clinical Scenarios: Case 1 – Metastatic (M1b) disease with local chest wall pain and 3 month life expectancy: All respondents recommended palliative radiotherapy, and most (98%) did not recommend concurrent chemotherapy. The fractionation schemes most often used were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%).
Case 2 – Metastatic (M1a) disease with endobronchial tumor blockage: 87% of the respondents would use conventional radiotherapy for symptoms such as hemoptysis, intractable cough, and pain, and the remainder would use SBRT. Almost half of respondents (49%) recommended EBB or YAG lung re-expansion before external beam radiotherapy.
Conclusion: In our study of VHA ROs and their knowledge of management of advanced (M1a/M1b) lung cancer, we found no distinction in clinical decisions based on demographic profiles. Almost all reported knowledge of evidence-based treatment guidelines for palliative radiotherapy of lung cancer and most recommended treatment according to current guidelines.”
Clinical trial enrollment linked to lower death rate in lung cancer patients
ALEXANDRIA, VA. – Patients with metastatic non–small cell lung cancer (NSCLC) who enrolled in clinical trials had a near 50% lower risk of death versus patients who received treatment outside a clinical trial, according to results of a single-center, retrospective medical record review.
Median survival was almost doubled for those patients with NSCLC enrolled in therapeutic drug trials, according to lead author Christina Merkhofer, MD, a hematology-oncology fellow at the University of Washington and Fred Hutchinson Cancer Center, both in Seattle.
The findings suggest that clinical trials, beyond supporting drug development, provide a direct benefit to NSCLC patients through provision of promising agents, enhanced supportive care, or both, according to Dr. Merkhofer and coauthors, who will present their findings in a poster at the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
The retrospective study included a total of 371 patients diagnosed with metastatic NSCLC between 2001 and 2015, of whom 118 (32%) enrolled in at least one clinical trial, Dr. Merkhofer reported at a press briefing ahead of the symposium.
Median survival was 838 days for the clinical trial enrollees versus 454 days for nonenrollees, according to the investigators. The risk of death was 47% lower (hazard ratio, 0.53; 95% confidence interval, 0.13-0.92; P = .002) for enrollees relative to nonenrollees after adjustment for variables including sex, performance status, smoking history, histology, presence of brain metastases, and EGFR/ALK status.
Based on this study by Dr. Merkhofer and colleagues, participating in therapeutic drug trials appears to improve survival in patients with advanced lung cancer, ASCO expert Merry-Jennifer Markham, MD, said in a statement.
Oncologists have a “duty” to enroll patients in clinical trials as appropriate, said Dr. Markham, chair of the Quality Care Symposium’s news planning team.
“We must work to better understand factors associated with enrollment so that the prospective benefits can be made accessible to all who are eligible,” she said.
The research is part of a larger investigation looking at “areas of uncertainty” in clinical trial participation, such as whether specific trial design characteristics are linked to survival benefit, according to Dr. Merkhofer.
“The study can support research evaluating health care policies or research that looks at incentives for patient participation in trials, such as financing transportation or lodging, [and] can help with research that addresses some of these important barriers to trial participation,” Dr. Merkhofer said in an ASCO press release.
Dr. Merkhofer had no disclosures related to the study. Her coauthors reported disclosures related to numerous pharmaceutical companies.
SOURCE: Merkhofer C et al. QCS2019, Abstract 137.
ALEXANDRIA, VA. – Patients with metastatic non–small cell lung cancer (NSCLC) who enrolled in clinical trials had a near 50% lower risk of death versus patients who received treatment outside a clinical trial, according to results of a single-center, retrospective medical record review.
Median survival was almost doubled for those patients with NSCLC enrolled in therapeutic drug trials, according to lead author Christina Merkhofer, MD, a hematology-oncology fellow at the University of Washington and Fred Hutchinson Cancer Center, both in Seattle.
The findings suggest that clinical trials, beyond supporting drug development, provide a direct benefit to NSCLC patients through provision of promising agents, enhanced supportive care, or both, according to Dr. Merkhofer and coauthors, who will present their findings in a poster at the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
The retrospective study included a total of 371 patients diagnosed with metastatic NSCLC between 2001 and 2015, of whom 118 (32%) enrolled in at least one clinical trial, Dr. Merkhofer reported at a press briefing ahead of the symposium.
Median survival was 838 days for the clinical trial enrollees versus 454 days for nonenrollees, according to the investigators. The risk of death was 47% lower (hazard ratio, 0.53; 95% confidence interval, 0.13-0.92; P = .002) for enrollees relative to nonenrollees after adjustment for variables including sex, performance status, smoking history, histology, presence of brain metastases, and EGFR/ALK status.
Based on this study by Dr. Merkhofer and colleagues, participating in therapeutic drug trials appears to improve survival in patients with advanced lung cancer, ASCO expert Merry-Jennifer Markham, MD, said in a statement.
Oncologists have a “duty” to enroll patients in clinical trials as appropriate, said Dr. Markham, chair of the Quality Care Symposium’s news planning team.
“We must work to better understand factors associated with enrollment so that the prospective benefits can be made accessible to all who are eligible,” she said.
The research is part of a larger investigation looking at “areas of uncertainty” in clinical trial participation, such as whether specific trial design characteristics are linked to survival benefit, according to Dr. Merkhofer.
“The study can support research evaluating health care policies or research that looks at incentives for patient participation in trials, such as financing transportation or lodging, [and] can help with research that addresses some of these important barriers to trial participation,” Dr. Merkhofer said in an ASCO press release.
Dr. Merkhofer had no disclosures related to the study. Her coauthors reported disclosures related to numerous pharmaceutical companies.
SOURCE: Merkhofer C et al. QCS2019, Abstract 137.
ALEXANDRIA, VA. – Patients with metastatic non–small cell lung cancer (NSCLC) who enrolled in clinical trials had a near 50% lower risk of death versus patients who received treatment outside a clinical trial, according to results of a single-center, retrospective medical record review.
Median survival was almost doubled for those patients with NSCLC enrolled in therapeutic drug trials, according to lead author Christina Merkhofer, MD, a hematology-oncology fellow at the University of Washington and Fred Hutchinson Cancer Center, both in Seattle.
The findings suggest that clinical trials, beyond supporting drug development, provide a direct benefit to NSCLC patients through provision of promising agents, enhanced supportive care, or both, according to Dr. Merkhofer and coauthors, who will present their findings in a poster at the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
The retrospective study included a total of 371 patients diagnosed with metastatic NSCLC between 2001 and 2015, of whom 118 (32%) enrolled in at least one clinical trial, Dr. Merkhofer reported at a press briefing ahead of the symposium.
Median survival was 838 days for the clinical trial enrollees versus 454 days for nonenrollees, according to the investigators. The risk of death was 47% lower (hazard ratio, 0.53; 95% confidence interval, 0.13-0.92; P = .002) for enrollees relative to nonenrollees after adjustment for variables including sex, performance status, smoking history, histology, presence of brain metastases, and EGFR/ALK status.
Based on this study by Dr. Merkhofer and colleagues, participating in therapeutic drug trials appears to improve survival in patients with advanced lung cancer, ASCO expert Merry-Jennifer Markham, MD, said in a statement.
Oncologists have a “duty” to enroll patients in clinical trials as appropriate, said Dr. Markham, chair of the Quality Care Symposium’s news planning team.
“We must work to better understand factors associated with enrollment so that the prospective benefits can be made accessible to all who are eligible,” she said.
The research is part of a larger investigation looking at “areas of uncertainty” in clinical trial participation, such as whether specific trial design characteristics are linked to survival benefit, according to Dr. Merkhofer.
“The study can support research evaluating health care policies or research that looks at incentives for patient participation in trials, such as financing transportation or lodging, [and] can help with research that addresses some of these important barriers to trial participation,” Dr. Merkhofer said in an ASCO press release.
Dr. Merkhofer had no disclosures related to the study. Her coauthors reported disclosures related to numerous pharmaceutical companies.
SOURCE: Merkhofer C et al. QCS2019, Abstract 137.
REPORTING FROM QCS 2019
Out-of-pocket cost of oral TKIs linked to poor lung cancer survival
ALEXANDRIA, VA. – Higher out-of-pocket costs for oral tyrosine kinase inhibitors (TKIs) were linked to inferior survival in patients with advanced, biomarker-positive lung cancers in an analysis of state-level registry data, an investigator reported at a press conference ahead of the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
Higher out-of-pocket cost burden was also linked to lower numbers of TKI prescriptions and shorter duration of TKI therapy in the study, which included patients diagnosed with EGFR- and ALK-positive non–small cell lung cancer (NSCLC) between 2010 and 2016.
The findings would suggest a need for a review of coverage for these effective medications, according to Bernardo H. L. Goulart, MD, a thoracic oncologist and health services researcher at the University of Washington and Fred Hutchinson Cancer Research Center, both in Seattle.
“Making sure that the cost to the patients is affordable could mitigate this financial toxicity, and hopefully help patients stay on therapy and derive the survival benefit that these medications are supposed to offer,” Dr. Goulart said in an interview.
The study included data on 106 patients with EGFR- and ALK-positive stage IV NSCLC in the Washington Surveillance, Epidemiology, and End Results registry who had at least one oral TKI prescription. Investigators linked that registry data with commercial and Medicare claims, then divided this patient cohort into quartiles based on out-of-pocket costs.
In the top quartile, the median monthly out-of-pocket cost for TKI treatment was $2,888, compared with just $1,431 in the other three quartiles – essentially half the cost, Dr. Goulart said.
Median survival in the patients in the top out-of-pocket cost quartile was just 9 months, compared with 22 months in the lower three quartiles, he added.
“That difference is remarkable,” Dr. Goulart said, adding that the survival in the top-cost quartile reflects a survival that might be expected with conventional, nontargeted chemotherapy, while survival in the remaining patients mirrored what might be expected based on clinical trials of TKIs in this setting.
Patients in the high-cost quartile were 2.31 times as likely to die as patients in the lower quartiles, according to results of a multivariable analysis that adjusted for patient, disease-specific, and financial characteristics including qualification for low-income subsidies.
The mean medication possession ratio, a measure of medication adherence, was lower in the high-cost quartile (1.06 vs. 1.20 for the lower three quartiles; P = .02), and median duration of therapy was likewise lower in the high-cost quartile (4 vs. 8 months; P less than .01), according to data reported in the study abstract.
While multiple previous studies have linked out-of-pocket costs to decreased adherence and duration of therapy, the present study is one of the few to evaluate the link between cost of oral cancer medications and survival, according to Dr. Goulart.
In one other recent study showing a relationship between financial toxicity and survival, researchers at Fred Hutch showing that Washington cancer patients who filed for bankruptcy were more likely to die, compared with cancer patients not filing for bankruptcy, even after adjustment for a variety of patient characteristics.
The present study results raise a “serious concern” that some patients are unable to afford their medications, which is having a detrimental effect on survival, Dr. Goulart said. Alternatively, the out-of-pocket costs may not have an effect on survival; rather, they may be a “marker of very poor insurance coverage” that reflects higher costs for multiple other aspects of their care.
“The out-of-pocket cost for these drugs can be pretty astronomical, and we have at least a plausible hypothesis that they are taking a toll on patient’s survival,” he added.
If the findings of this study are confirmed in more and larger studies, there could be important implications for health policy and oncology practice, according to Dr. Goulart.
“The biggest action would be to involve patient advocates and physician groups such as ASCO, and advocate for changes in policy for coverage and out-of-pocket costs for these oral TKIs, at least for the patients that have the mutations,” he explained.
Another action, according to Dr. Goulart, would be to try to equip oncology clinics everywhere with patient financial-assistance programs to link patients to entities that can help them afford the cost of TKIs.
“Patients who attend small, remote cancer clinics might not have access to a financial specialist who can help them navigate these costs,” he said.
Funding for the study came from the National Institutes of Health. Dr. Goulart reported disclosures related to Flatiron Health (travel, accommodations, and expenses).
SOURCE: Goulart BHL et al. SCS 2019, Abstract 3.
ALEXANDRIA, VA. – Higher out-of-pocket costs for oral tyrosine kinase inhibitors (TKIs) were linked to inferior survival in patients with advanced, biomarker-positive lung cancers in an analysis of state-level registry data, an investigator reported at a press conference ahead of the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
Higher out-of-pocket cost burden was also linked to lower numbers of TKI prescriptions and shorter duration of TKI therapy in the study, which included patients diagnosed with EGFR- and ALK-positive non–small cell lung cancer (NSCLC) between 2010 and 2016.
The findings would suggest a need for a review of coverage for these effective medications, according to Bernardo H. L. Goulart, MD, a thoracic oncologist and health services researcher at the University of Washington and Fred Hutchinson Cancer Research Center, both in Seattle.
“Making sure that the cost to the patients is affordable could mitigate this financial toxicity, and hopefully help patients stay on therapy and derive the survival benefit that these medications are supposed to offer,” Dr. Goulart said in an interview.
The study included data on 106 patients with EGFR- and ALK-positive stage IV NSCLC in the Washington Surveillance, Epidemiology, and End Results registry who had at least one oral TKI prescription. Investigators linked that registry data with commercial and Medicare claims, then divided this patient cohort into quartiles based on out-of-pocket costs.
In the top quartile, the median monthly out-of-pocket cost for TKI treatment was $2,888, compared with just $1,431 in the other three quartiles – essentially half the cost, Dr. Goulart said.
Median survival in the patients in the top out-of-pocket cost quartile was just 9 months, compared with 22 months in the lower three quartiles, he added.
“That difference is remarkable,” Dr. Goulart said, adding that the survival in the top-cost quartile reflects a survival that might be expected with conventional, nontargeted chemotherapy, while survival in the remaining patients mirrored what might be expected based on clinical trials of TKIs in this setting.
Patients in the high-cost quartile were 2.31 times as likely to die as patients in the lower quartiles, according to results of a multivariable analysis that adjusted for patient, disease-specific, and financial characteristics including qualification for low-income subsidies.
The mean medication possession ratio, a measure of medication adherence, was lower in the high-cost quartile (1.06 vs. 1.20 for the lower three quartiles; P = .02), and median duration of therapy was likewise lower in the high-cost quartile (4 vs. 8 months; P less than .01), according to data reported in the study abstract.
While multiple previous studies have linked out-of-pocket costs to decreased adherence and duration of therapy, the present study is one of the few to evaluate the link between cost of oral cancer medications and survival, according to Dr. Goulart.
In one other recent study showing a relationship between financial toxicity and survival, researchers at Fred Hutch showing that Washington cancer patients who filed for bankruptcy were more likely to die, compared with cancer patients not filing for bankruptcy, even after adjustment for a variety of patient characteristics.
The present study results raise a “serious concern” that some patients are unable to afford their medications, which is having a detrimental effect on survival, Dr. Goulart said. Alternatively, the out-of-pocket costs may not have an effect on survival; rather, they may be a “marker of very poor insurance coverage” that reflects higher costs for multiple other aspects of their care.
“The out-of-pocket cost for these drugs can be pretty astronomical, and we have at least a plausible hypothesis that they are taking a toll on patient’s survival,” he added.
If the findings of this study are confirmed in more and larger studies, there could be important implications for health policy and oncology practice, according to Dr. Goulart.
“The biggest action would be to involve patient advocates and physician groups such as ASCO, and advocate for changes in policy for coverage and out-of-pocket costs for these oral TKIs, at least for the patients that have the mutations,” he explained.
Another action, according to Dr. Goulart, would be to try to equip oncology clinics everywhere with patient financial-assistance programs to link patients to entities that can help them afford the cost of TKIs.
“Patients who attend small, remote cancer clinics might not have access to a financial specialist who can help them navigate these costs,” he said.
Funding for the study came from the National Institutes of Health. Dr. Goulart reported disclosures related to Flatiron Health (travel, accommodations, and expenses).
SOURCE: Goulart BHL et al. SCS 2019, Abstract 3.
ALEXANDRIA, VA. – Higher out-of-pocket costs for oral tyrosine kinase inhibitors (TKIs) were linked to inferior survival in patients with advanced, biomarker-positive lung cancers in an analysis of state-level registry data, an investigator reported at a press conference ahead of the Quality Care Symposium, sponsored by the American Society of Clinical Oncology.
Higher out-of-pocket cost burden was also linked to lower numbers of TKI prescriptions and shorter duration of TKI therapy in the study, which included patients diagnosed with EGFR- and ALK-positive non–small cell lung cancer (NSCLC) between 2010 and 2016.
The findings would suggest a need for a review of coverage for these effective medications, according to Bernardo H. L. Goulart, MD, a thoracic oncologist and health services researcher at the University of Washington and Fred Hutchinson Cancer Research Center, both in Seattle.
“Making sure that the cost to the patients is affordable could mitigate this financial toxicity, and hopefully help patients stay on therapy and derive the survival benefit that these medications are supposed to offer,” Dr. Goulart said in an interview.
The study included data on 106 patients with EGFR- and ALK-positive stage IV NSCLC in the Washington Surveillance, Epidemiology, and End Results registry who had at least one oral TKI prescription. Investigators linked that registry data with commercial and Medicare claims, then divided this patient cohort into quartiles based on out-of-pocket costs.
In the top quartile, the median monthly out-of-pocket cost for TKI treatment was $2,888, compared with just $1,431 in the other three quartiles – essentially half the cost, Dr. Goulart said.
Median survival in the patients in the top out-of-pocket cost quartile was just 9 months, compared with 22 months in the lower three quartiles, he added.
“That difference is remarkable,” Dr. Goulart said, adding that the survival in the top-cost quartile reflects a survival that might be expected with conventional, nontargeted chemotherapy, while survival in the remaining patients mirrored what might be expected based on clinical trials of TKIs in this setting.
Patients in the high-cost quartile were 2.31 times as likely to die as patients in the lower quartiles, according to results of a multivariable analysis that adjusted for patient, disease-specific, and financial characteristics including qualification for low-income subsidies.
The mean medication possession ratio, a measure of medication adherence, was lower in the high-cost quartile (1.06 vs. 1.20 for the lower three quartiles; P = .02), and median duration of therapy was likewise lower in the high-cost quartile (4 vs. 8 months; P less than .01), according to data reported in the study abstract.
While multiple previous studies have linked out-of-pocket costs to decreased adherence and duration of therapy, the present study is one of the few to evaluate the link between cost of oral cancer medications and survival, according to Dr. Goulart.
In one other recent study showing a relationship between financial toxicity and survival, researchers at Fred Hutch showing that Washington cancer patients who filed for bankruptcy were more likely to die, compared with cancer patients not filing for bankruptcy, even after adjustment for a variety of patient characteristics.
The present study results raise a “serious concern” that some patients are unable to afford their medications, which is having a detrimental effect on survival, Dr. Goulart said. Alternatively, the out-of-pocket costs may not have an effect on survival; rather, they may be a “marker of very poor insurance coverage” that reflects higher costs for multiple other aspects of their care.
“The out-of-pocket cost for these drugs can be pretty astronomical, and we have at least a plausible hypothesis that they are taking a toll on patient’s survival,” he added.
If the findings of this study are confirmed in more and larger studies, there could be important implications for health policy and oncology practice, according to Dr. Goulart.
“The biggest action would be to involve patient advocates and physician groups such as ASCO, and advocate for changes in policy for coverage and out-of-pocket costs for these oral TKIs, at least for the patients that have the mutations,” he explained.
Another action, according to Dr. Goulart, would be to try to equip oncology clinics everywhere with patient financial-assistance programs to link patients to entities that can help them afford the cost of TKIs.
“Patients who attend small, remote cancer clinics might not have access to a financial specialist who can help them navigate these costs,” he said.
Funding for the study came from the National Institutes of Health. Dr. Goulart reported disclosures related to Flatiron Health (travel, accommodations, and expenses).
SOURCE: Goulart BHL et al. SCS 2019, Abstract 3.
REPORTING FROM QCS 2019
Lung Cancer – Regional Snapshot Kansas City VA
Open Clinical Trials for Patients With Lung Cancers (FULL)
Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting patients from those patient populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors or cosponsors nearly 1,000 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of August 1, 201 8 ; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for colorectal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Lung-MAP (multiple trials)
Lung-MAP (SWOG S1400) is a multidrug, multi-substudy, biomarker-driven squamous cell lung cancer clinical trial that uses state-of-the-art genomic profiling to match patients to substudies testing investigational treatments that may target the genomic alterations, or mutations, found to be driving the growth of their cancer.
ID: NCT02154490, NCT02595944, NCT02766335, NCT02785913, NCT02785939, NCT02926638, NCT02965378, NCT03373760, NCT03377556
Sponsor: Southwest Oncology Group
Locations: VA Connecticut Healthcare System-West Haven Campus; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Ann Arbor VAMC, Michigan; Kansas City VAMC, Missouri; VA New Jersey Health Care System, East Orange; Michael E. DeBakey VAMC Houston, Texas
ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (multiple trials)
A group of randomized clinical trials for patients with early-stage non-small cell lung cancer whose tumors have been completely removed by surgery.
ID: NCT02193282, NCT02194738, NCT02201992, NCT02595944
Sponsor: National Cancer Institute
Locations: Little Rock VAMC, Arkansas; VA Connecticut Healthcare System West Haven Campus; Atlanta VAMC, Decatur, Georgia; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Minneapolis VAMC, Minnesota; Saint Louis VAMC, Missouri; Veterans Affairs New York Harbor Healthcare System-Brooklyn Campus; Dayton VAMC, Ohio; William S. Middleton VAMC, Madison, Wisconsin
Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy (VALOR)
The standard of care for stage I non-small cell lung cancer has historically been surgical resection in patients who are medically fit to tolerate an operation. Recent data now suggests that stereotactic radiotherapy may be a suitable alternative. This includes the results from a pooled analysis of two incomplete phase III studies that reported a 15% overall survival advantage with stereotactic radiotherapy at 3 years. While these data are promising, the median follow-up period was short, the results underpowered, and the findings were in contradiction to multiple retrospective studies that demonstrate the outcomes with surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two treatments in a prospective randomized fashion with a goal to compare the overall survival beyond 5 years. It has been designed to enroll patients who have a long life-expectancy, and are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node sampling.
ID: NCT02984761
Sponsor: VA Office of Research and Development
Locations: Edward Hines Jr. VA Hospital, Hines, Illinois; Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; Minneapolis VA Health Care System, Minnesota; Durham VAMC, North Carolina; Michael E. DeBakey VAMC, Houston, Texas; Hunter Holmes McGuire VA Medical Center, Richmond, Virginia
Naloxegol in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer
This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.
ID: NCT03087708
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Minneapolis VAMC, Minnesota; Kansas City VAMC, Missouri; VA Western New York Health Care System-Buffalo; Salisbury VAMC, North Carolina
Palliative Care Interventions for Outpatients Newly Diagnosed With Lung Cancer: Phase II (PCI2)
The focus of the study is to test a nurse-led telephone-based palliative care intervention on improving the delivery of care for patients with newly diagnosed lung cancer. The study is a three site randomized control trial to determine the efficacy of the intervention on improving patients’ quality of life, symptom burden, and satisfaction of care. Additionally, the study will test an innovative care delivery model to improve patients’ access to palliative care. The investigators will also determine the effect of the intervention on patient activation to discuss treatment preferences with their clinician and on clinician knowledge of patients’ goals of care.
ID: NCT03007953
Sponsor: VA Office of Research and Development
Locations: Birmingham VAMC, Alabama; VA Portland Health Care System, Oregon; VA Puget Sound Health Care System Seattle Division, Washington
Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.
ID: NCT00632853
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Baltimore VAMC, Maryland; Kansas City VAMC, Missouri; VA Western New York Health Care System, Buffalo, New York; Dayton VAMC, Ohio; Zablocki VAMC, Milwaukee, Wisconsin
Comparison of Different Types of Surgery in Treating Patients With Stage IA Non-Small Cell Lung Cancer
Wedge resection or segmentectomy may be less invasive types of surgery than lobectomy for non-small cell lung cancer and may have fewer side effects and improve recovery. It is not yet known whether wedge resection or segmentectomy are more effective than lobectomy in treating stage IA non-small cell lung cancer.
ID: NCT00499330
Sponsor: Alliance for Clinical Trials in Oncology
Locations: VA Loma Linda Healthcare System, California; VA Long Beach Medical Center, California; Richard L. Roudebush VAMC, Indianapolis, Indiana; Portland VAMC, Oregon
Lung Cancer Screening Decisions (VA-LCSDecTool)
Veterans have a high risk of developing lung in comparison to general populations due to their older age and smoking history. Recent evidence indicates that lung cancer screening with low dose CT scan reduces lung cancer mortality among older heavy smokers. However, the rates of false positive findings are high, requiring further testing and evaluation. Preliminary studies report that while some Veterans are enthusiastic about screening, others are highly reluctant. Patient preferences should be considered as part of an informed decision making process for this emerging paradigm of lung cancer control. Effective methods for preference assessment among Veterans have not yet been developed, evaluated, and integrated into clinical practice. The specific aims of this study are to 1) elicit patient and provider stakeholder input to inform the development of a lung cancer screening decision tool, 2) develop a web based Lung Cancer Screening Decision Tool (LCSDecTool) that incorporates patient and provider input, and 3) evaluate the impact of the LCSDecTool compared to usual care on the decision process, clinical outcomes, and quality of life.
ID
Sponsor: VA Office of Research and Development
Locations: VA Connecticut Healthcare System West Haven Campus; Corporal Michael J. Crescenz VAMC Philadelphia, Pennsylvania
Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer
Using samples of blood, urine, sputum, and lung tissue from patients at high risk of cancer for laboratory studies may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.
ID: NCT00898313
Sponsor: Vanderbilt-Ingram Cancer Center
Location: VAMC Nashville, Tennessee
Improving Supportive Care for Patients With Thoracic Malignancies
The purpose of this study is to use a proactive approach to improve symptom management of patients with thoracic malignancies. In this pilot study, the investigators propose to evaluate the feasibility of using outbound, proactive telephone symptom assessment strategies and measure the efficacy of this approach on patient satisfaction with their care, patient activation, quality of life and use of healthcare resources.
ID: NCT03216109
Sponsor: Palo Alto Veterans Institute for Research
Location: VA Palo Alto Health Care System, California
Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting patients from those patient populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors or cosponsors nearly 1,000 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of August 1, 201 8 ; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for colorectal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Lung-MAP (multiple trials)
Lung-MAP (SWOG S1400) is a multidrug, multi-substudy, biomarker-driven squamous cell lung cancer clinical trial that uses state-of-the-art genomic profiling to match patients to substudies testing investigational treatments that may target the genomic alterations, or mutations, found to be driving the growth of their cancer.
ID: NCT02154490, NCT02595944, NCT02766335, NCT02785913, NCT02785939, NCT02926638, NCT02965378, NCT03373760, NCT03377556
Sponsor: Southwest Oncology Group
Locations: VA Connecticut Healthcare System-West Haven Campus; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Ann Arbor VAMC, Michigan; Kansas City VAMC, Missouri; VA New Jersey Health Care System, East Orange; Michael E. DeBakey VAMC Houston, Texas
ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (multiple trials)
A group of randomized clinical trials for patients with early-stage non-small cell lung cancer whose tumors have been completely removed by surgery.
ID: NCT02193282, NCT02194738, NCT02201992, NCT02595944
Sponsor: National Cancer Institute
Locations: Little Rock VAMC, Arkansas; VA Connecticut Healthcare System West Haven Campus; Atlanta VAMC, Decatur, Georgia; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Minneapolis VAMC, Minnesota; Saint Louis VAMC, Missouri; Veterans Affairs New York Harbor Healthcare System-Brooklyn Campus; Dayton VAMC, Ohio; William S. Middleton VAMC, Madison, Wisconsin
Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy (VALOR)
The standard of care for stage I non-small cell lung cancer has historically been surgical resection in patients who are medically fit to tolerate an operation. Recent data now suggests that stereotactic radiotherapy may be a suitable alternative. This includes the results from a pooled analysis of two incomplete phase III studies that reported a 15% overall survival advantage with stereotactic radiotherapy at 3 years. While these data are promising, the median follow-up period was short, the results underpowered, and the findings were in contradiction to multiple retrospective studies that demonstrate the outcomes with surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two treatments in a prospective randomized fashion with a goal to compare the overall survival beyond 5 years. It has been designed to enroll patients who have a long life-expectancy, and are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node sampling.
ID: NCT02984761
Sponsor: VA Office of Research and Development
Locations: Edward Hines Jr. VA Hospital, Hines, Illinois; Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; Minneapolis VA Health Care System, Minnesota; Durham VAMC, North Carolina; Michael E. DeBakey VAMC, Houston, Texas; Hunter Holmes McGuire VA Medical Center, Richmond, Virginia
Naloxegol in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer
This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.
ID: NCT03087708
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Minneapolis VAMC, Minnesota; Kansas City VAMC, Missouri; VA Western New York Health Care System-Buffalo; Salisbury VAMC, North Carolina
Palliative Care Interventions for Outpatients Newly Diagnosed With Lung Cancer: Phase II (PCI2)
The focus of the study is to test a nurse-led telephone-based palliative care intervention on improving the delivery of care for patients with newly diagnosed lung cancer. The study is a three site randomized control trial to determine the efficacy of the intervention on improving patients’ quality of life, symptom burden, and satisfaction of care. Additionally, the study will test an innovative care delivery model to improve patients’ access to palliative care. The investigators will also determine the effect of the intervention on patient activation to discuss treatment preferences with their clinician and on clinician knowledge of patients’ goals of care.
ID: NCT03007953
Sponsor: VA Office of Research and Development
Locations: Birmingham VAMC, Alabama; VA Portland Health Care System, Oregon; VA Puget Sound Health Care System Seattle Division, Washington
Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.
ID: NCT00632853
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Baltimore VAMC, Maryland; Kansas City VAMC, Missouri; VA Western New York Health Care System, Buffalo, New York; Dayton VAMC, Ohio; Zablocki VAMC, Milwaukee, Wisconsin
Comparison of Different Types of Surgery in Treating Patients With Stage IA Non-Small Cell Lung Cancer
Wedge resection or segmentectomy may be less invasive types of surgery than lobectomy for non-small cell lung cancer and may have fewer side effects and improve recovery. It is not yet known whether wedge resection or segmentectomy are more effective than lobectomy in treating stage IA non-small cell lung cancer.
ID: NCT00499330
Sponsor: Alliance for Clinical Trials in Oncology
Locations: VA Loma Linda Healthcare System, California; VA Long Beach Medical Center, California; Richard L. Roudebush VAMC, Indianapolis, Indiana; Portland VAMC, Oregon
Lung Cancer Screening Decisions (VA-LCSDecTool)
Veterans have a high risk of developing lung in comparison to general populations due to their older age and smoking history. Recent evidence indicates that lung cancer screening with low dose CT scan reduces lung cancer mortality among older heavy smokers. However, the rates of false positive findings are high, requiring further testing and evaluation. Preliminary studies report that while some Veterans are enthusiastic about screening, others are highly reluctant. Patient preferences should be considered as part of an informed decision making process for this emerging paradigm of lung cancer control. Effective methods for preference assessment among Veterans have not yet been developed, evaluated, and integrated into clinical practice. The specific aims of this study are to 1) elicit patient and provider stakeholder input to inform the development of a lung cancer screening decision tool, 2) develop a web based Lung Cancer Screening Decision Tool (LCSDecTool) that incorporates patient and provider input, and 3) evaluate the impact of the LCSDecTool compared to usual care on the decision process, clinical outcomes, and quality of life.
ID
Sponsor: VA Office of Research and Development
Locations: VA Connecticut Healthcare System West Haven Campus; Corporal Michael J. Crescenz VAMC Philadelphia, Pennsylvania
Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer
Using samples of blood, urine, sputum, and lung tissue from patients at high risk of cancer for laboratory studies may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.
ID: NCT00898313
Sponsor: Vanderbilt-Ingram Cancer Center
Location: VAMC Nashville, Tennessee
Improving Supportive Care for Patients With Thoracic Malignancies
The purpose of this study is to use a proactive approach to improve symptom management of patients with thoracic malignancies. In this pilot study, the investigators propose to evaluate the feasibility of using outbound, proactive telephone symptom assessment strategies and measure the efficacy of this approach on patient satisfaction with their care, patient activation, quality of life and use of healthcare resources.
ID: NCT03216109
Sponsor: Palo Alto Veterans Institute for Research
Location: VA Palo Alto Health Care System, California
Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting patients from those patient populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors or cosponsors nearly 1,000 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of August 1, 201 8 ; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for colorectal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Lung-MAP (multiple trials)
Lung-MAP (SWOG S1400) is a multidrug, multi-substudy, biomarker-driven squamous cell lung cancer clinical trial that uses state-of-the-art genomic profiling to match patients to substudies testing investigational treatments that may target the genomic alterations, or mutations, found to be driving the growth of their cancer.
ID: NCT02154490, NCT02595944, NCT02766335, NCT02785913, NCT02785939, NCT02926638, NCT02965378, NCT03373760, NCT03377556
Sponsor: Southwest Oncology Group
Locations: VA Connecticut Healthcare System-West Haven Campus; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Ann Arbor VAMC, Michigan; Kansas City VAMC, Missouri; VA New Jersey Health Care System, East Orange; Michael E. DeBakey VAMC Houston, Texas
ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (multiple trials)
A group of randomized clinical trials for patients with early-stage non-small cell lung cancer whose tumors have been completely removed by surgery.
ID: NCT02193282, NCT02194738, NCT02201992, NCT02595944
Sponsor: National Cancer Institute
Locations: Little Rock VAMC, Arkansas; VA Connecticut Healthcare System West Haven Campus; Atlanta VAMC, Decatur, Georgia; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; Minneapolis VAMC, Minnesota; Saint Louis VAMC, Missouri; Veterans Affairs New York Harbor Healthcare System-Brooklyn Campus; Dayton VAMC, Ohio; William S. Middleton VAMC, Madison, Wisconsin
Veterans Affairs Lung Cancer Or Stereotactic Radiotherapy (VALOR)
The standard of care for stage I non-small cell lung cancer has historically been surgical resection in patients who are medically fit to tolerate an operation. Recent data now suggests that stereotactic radiotherapy may be a suitable alternative. This includes the results from a pooled analysis of two incomplete phase III studies that reported a 15% overall survival advantage with stereotactic radiotherapy at 3 years. While these data are promising, the median follow-up period was short, the results underpowered, and the findings were in contradiction to multiple retrospective studies that demonstrate the outcomes with surgery are likely equal or superior. Therefore, the herein trial aims to evaluate these two treatments in a prospective randomized fashion with a goal to compare the overall survival beyond 5 years. It has been designed to enroll patients who have a long life-expectancy, and are fit enough to tolerate an anatomic pulmonary resection with intraoperative lymph node sampling.
ID: NCT02984761
Sponsor: VA Office of Research and Development
Locations: Edward Hines Jr. VA Hospital, Hines, Illinois; Richard L. Roudebush VA Medical Center, Indianapolis, Indiana; Minneapolis VA Health Care System, Minnesota; Durham VAMC, North Carolina; Michael E. DeBakey VAMC, Houston, Texas; Hunter Holmes McGuire VA Medical Center, Richmond, Virginia
Naloxegol in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer
This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.
ID: NCT03087708
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Minneapolis VAMC, Minnesota; Kansas City VAMC, Missouri; VA Western New York Health Care System-Buffalo; Salisbury VAMC, North Carolina
Palliative Care Interventions for Outpatients Newly Diagnosed With Lung Cancer: Phase II (PCI2)
The focus of the study is to test a nurse-led telephone-based palliative care intervention on improving the delivery of care for patients with newly diagnosed lung cancer. The study is a three site randomized control trial to determine the efficacy of the intervention on improving patients’ quality of life, symptom burden, and satisfaction of care. Additionally, the study will test an innovative care delivery model to improve patients’ access to palliative care. The investigators will also determine the effect of the intervention on patient activation to discuss treatment preferences with their clinician and on clinician knowledge of patients’ goals of care.
ID: NCT03007953
Sponsor: VA Office of Research and Development
Locations: Birmingham VAMC, Alabama; VA Portland Health Care System, Oregon; VA Puget Sound Health Care System Seattle Division, Washington
Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.
ID: NCT00632853
Sponsor: Alliance for Clinical Trials in Oncology
Locations: Baltimore VAMC, Maryland; Kansas City VAMC, Missouri; VA Western New York Health Care System, Buffalo, New York; Dayton VAMC, Ohio; Zablocki VAMC, Milwaukee, Wisconsin
Comparison of Different Types of Surgery in Treating Patients With Stage IA Non-Small Cell Lung Cancer
Wedge resection or segmentectomy may be less invasive types of surgery than lobectomy for non-small cell lung cancer and may have fewer side effects and improve recovery. It is not yet known whether wedge resection or segmentectomy are more effective than lobectomy in treating stage IA non-small cell lung cancer.
ID: NCT00499330
Sponsor: Alliance for Clinical Trials in Oncology
Locations: VA Loma Linda Healthcare System, California; VA Long Beach Medical Center, California; Richard L. Roudebush VAMC, Indianapolis, Indiana; Portland VAMC, Oregon
Lung Cancer Screening Decisions (VA-LCSDecTool)
Veterans have a high risk of developing lung in comparison to general populations due to their older age and smoking history. Recent evidence indicates that lung cancer screening with low dose CT scan reduces lung cancer mortality among older heavy smokers. However, the rates of false positive findings are high, requiring further testing and evaluation. Preliminary studies report that while some Veterans are enthusiastic about screening, others are highly reluctant. Patient preferences should be considered as part of an informed decision making process for this emerging paradigm of lung cancer control. Effective methods for preference assessment among Veterans have not yet been developed, evaluated, and integrated into clinical practice. The specific aims of this study are to 1) elicit patient and provider stakeholder input to inform the development of a lung cancer screening decision tool, 2) develop a web based Lung Cancer Screening Decision Tool (LCSDecTool) that incorporates patient and provider input, and 3) evaluate the impact of the LCSDecTool compared to usual care on the decision process, clinical outcomes, and quality of life.
ID
Sponsor: VA Office of Research and Development
Locations: VA Connecticut Healthcare System West Haven Campus; Corporal Michael J. Crescenz VAMC Philadelphia, Pennsylvania
Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer
Using samples of blood, urine, sputum, and lung tissue from patients at high risk of cancer for laboratory studies may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.
ID: NCT00898313
Sponsor: Vanderbilt-Ingram Cancer Center
Location: VAMC Nashville, Tennessee
Improving Supportive Care for Patients With Thoracic Malignancies
The purpose of this study is to use a proactive approach to improve symptom management of patients with thoracic malignancies. In this pilot study, the investigators propose to evaluate the feasibility of using outbound, proactive telephone symptom assessment strategies and measure the efficacy of this approach on patient satisfaction with their care, patient activation, quality of life and use of healthcare resources.
ID: NCT03216109
Sponsor: Palo Alto Veterans Institute for Research
Location: VA Palo Alto Health Care System, California