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New cell-free DNA assays hold promise for lung cancer screening
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
CHICAGO – according to the first interim report from a substudy of the large, ongoing Circulating Cell-free Genome Atlas (CCGA).
“Lung cancer screening with low-dose CT is known to improve outcomes. And yet, CT-based lung cancer screening is not widely adopted,” said lead study author Geoffrey R. Oxnard, MD, associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, Boston, in a press briefing at the annual meeting of the American Society of Clinical Oncology, where the study was reported. “Criticisms of low-dose CT include the risk of false positives and overdiagnosis. We proposed to investigate an untapped opportunity for cancer detection, which is using cell-free DNA.”
Main substudy results among 164 patients with lung cancer and 923 comparable individuals without known cancer showed that at a specificity of 98%, the three assays evaluated detected up to 51% of early-stage (stage I-IIIA) lung cancers and up to 91% of late-stage (stage IIIB-IV) lung cancers. And among the healthy participants with false-positive results for lung cancer, several were ultimately found to have cancers of other types.
“This first interim analysis of the CCGA study demonstrates that comprehensive sequencing of the plasma cell-free DNA can generate high-quality data across the entire genome, and it permits noninvasive cancer detection. The assays can detect lung cancer across stages, across histologies, across populations,” Dr. Oxnard said.
“Together, these results support the promise of using cell-free, DNA-based assays to develop an early cancer detection test with high specificity. Further assay and clinical development is ongoing: There is a separate prospective trial enrolling, the STRIVE study, and there remain thousands of patients still on this CCGA study to be analyzed for further optimization and focusing of this assay towards an eventual cancer diagnostic.”
The cohort studied was not a screening population, so the assays’ performance cannot be compared with that of low-dose CT at this point, he said. But the hypothesis going forward is that the assays will have comparatively higher specificity, sparing some patients an unnecessary diagnostic work-up.
The population in which the final blood test might be used will depend on its diagnostic performance once the assays are fully refined and clinic ready, which will take some time, according to Dr. Oxnard. However, “2 years ago, this was a pipe dream. Two years ago, it was completely just a brainstorm that had no data to support it, and I didn’t believe that this could be done. Today, we actually have data to show that this is really feasible to find early-stage cancer in the blood. So this is a huge step forward and actually means that this is going to be a reality.”
“This is an important first step towards an easier way to detect lung cancer at earlier and hopefully more curable stages,” agreed ASCO Expert David Graham, MD, who is also medical director at the Levine Cancer Institute in Charlotte, N.C. “If the promise of this report holds, we could easily see a day when a person could be screened for lung cancer and possibly other cancers simply by going into their regular doctor’s office for a blood draw.”
Study details
The CCGA study has enrolled more than 12,000 of its planned 15,000 participants (70% with cancer, 30% without) across 142 U.S. and Canadian sites.
The substudy reported had a development cohort (118 patients with lung cancer, 561 individuals without cancer) and a validation cohort (46 patients with lung cancer, 362 individuals without cancer), with the lung cancer and noncancer groups matched on age, race, and body mass index. “Having a comparable control cohort is very important in developing such a diagnostic for accurate analysis of the potential false-positive rate,” Dr. Oxnard noted.
Three prototype assays were tested: A targeted sequencing assay entailing very deep sequencing across 507 genes for somatic mutations such as single-nucleotide variants and small insertions and/or deletions; a novel, whole-genome sequencing assay to detect somatic gene copy number changes; and a novel, whole-genome methylation sequencing assay to detect abnormal epigenetic changes.
Sequencing was also performed on DNA from white blood cells. “That’s very important. The white blood cells are rich with mutations that can pollute the DNA and make you think that there is cancer present in the cell-free DNA,” Dr. Oxnard explained. “You screen out this interference from the white blood cells and other biologic noise, and you are left with the final features: mutations, copy number variations, and methylation signatures that then go into the final assays being studied.”
Results showed that when assay specificity was 98%, sensitivity for early-stage (stage I-IIIA) lung cancer ranged from 38% to 51%, and sensitivity for late-stage (stage IIIB-IV) lung cancer ranged from 87% to 91%.
Among five presumed cancer-free individuals having positive results on all three assays, two subsequently received a cancer diagnosis (one with stage III ovarian cancer, one with stage II endometrial cancer).
An additional 19 cancer types across all stages were tested in the CCGA substudy. Early results for breast, gastrointestinal, gynecologic, blood, and other cancers were also reported at the meeting (abstracts 536, 12021, and 12003).
Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
SOURCE: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
REPORTING FROM ASCO 2018
Key clinical point: Three blood-based assays performed moderately well for identifying lung cancer in early, potentially curable stages.
Major finding: At 98% specificity, the assays had sensitivities of 38%-51% for detecting lung cancers of stage I-IIIA.
Study details: A case-control study of circulating cell-free DNA assays among 164 patients with lung cancer and 923 comparable individuals without cancer.
Disclosures: Dr. Oxnard disclosed that he has a consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech/Roche, Novartis, Loxo Oncology, Ignyta, DropWorks, and GRAIL, and that he has patents, royalties, and/or other intellectual property with Chugai Pharmaceutical, Bio-Rad, Sysmex, and Guardant Health. The study was funded by GRAIL.
Source: Oxnard GR et al. ASCO 2018. Abstract LBA8501.
H&N cancer may be undertreated in women
CHICAGO – Sex disparities in the treatment of head and neck cancer may be leading to poorer outcomes for women, according to a retrospective registry-based cohort study of 884 patients reported at annual meeting of the American Society of Clinical Oncology.
“The treatment of head and neck cancer often requires intensive treatment that can have lasting side effects,” senior study author Jed A. Katzel, MD, a medical oncologist at Kaiser Permanente in Santa Clara, Calif., said in a press briefing. “Our goal was to review data from a large group of patients in Northern California to determine which patients are most likely to benefit from aggressive therapy, while minimizing toxicity for those likely to die from competing events.”
The reasons for the observed sex disparities are not known, according to Dr. Katzel. However, they may include patient preferences, physician practices, and the higher proportion among men of oropharynx tumors, as those tumors are more commonly associated with human papillomavirus (HPV), which carries a more favorable prognosis.
“Further investigation is needed to determine if there is an actual difference in treatment and outcomes for women, compared with men,” he said. “To this end, we have planned a chart-by-chart review, as well as a prospective analysis that will be performed in the currently enrolling NRG HN004 clinical trial.”
“The outcome of this study was very surprising to us, the idea that there are disparities in both the treatment that women receive relative to men, but also in the rate of death from head and neck cancer for women compared to men,” commented ASCO Expert Joshua Jones, MD, MA, who is also a radiation oncologist at the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia.
Dr. Katzel and his colleagues used the Kaiser Permanente Northern California registry to identify patients with stage II to IVB head and neck cancer diagnosed during 2000-2015.
Analyses were based on 223 women and 661 men, relative numbers that are not surprising given the known demographics of this cancer. Oropharyngeal tumors accounted for 38% of the cancers in the former, but 55% in the latter. (HPV status was not directly ascertained.)
The rate of receipt of intensive chemotherapy was 35% for women and 46% for men (adjusted odds ratio, 0.68; 95% CI, 0.48-0.98; P = .006). Similarly, the rate of receipt of radiation therapy was 60% for women and 70% for men (AOR, 0.79; 95% CI, 0.56-1.11; P = .008). Receipt of surgery was similar for the sexes.
The investigators analyzed deaths according to type using a GCE model that controlled for age, sex, tumor site, and Charlson Comorbidity Index. “The GCE model essentially describes the degree to which cancer is the patient’s problem,” Dr. Katzel explained.
Results showed that both women and men were more likely to die from cancer than from other causes; however, the ratio was 7 for women, compared with just 3.8 for men, a difference translating to a relative hazard ratio of 1.92 (95% CI, 1.07-3.43).
In terms of potential confounding, there were only 19 noncancer deaths among the women studied, suggesting that they may have been more healthy than the men, which could have influenced the calculations, according to Dr. Katzel.
“This GCE model has been validated in head and neck cancer, but also in breast cancer, prostate cancer, and endometrial cancer, so we are using a validated model to do this evaluation,” he noted. “So I would say we are confident in our findings.”
Dr. Katzel disclosed that he had no relevant conflicts of interest. The study received funding from Kaiser Permanente Northern California Graduate Medical Education Department.
SOURCE: Park A et al. ASCO 2018 Abstract LBA6002.
CHICAGO – Sex disparities in the treatment of head and neck cancer may be leading to poorer outcomes for women, according to a retrospective registry-based cohort study of 884 patients reported at annual meeting of the American Society of Clinical Oncology.
“The treatment of head and neck cancer often requires intensive treatment that can have lasting side effects,” senior study author Jed A. Katzel, MD, a medical oncologist at Kaiser Permanente in Santa Clara, Calif., said in a press briefing. “Our goal was to review data from a large group of patients in Northern California to determine which patients are most likely to benefit from aggressive therapy, while minimizing toxicity for those likely to die from competing events.”
The reasons for the observed sex disparities are not known, according to Dr. Katzel. However, they may include patient preferences, physician practices, and the higher proportion among men of oropharynx tumors, as those tumors are more commonly associated with human papillomavirus (HPV), which carries a more favorable prognosis.
“Further investigation is needed to determine if there is an actual difference in treatment and outcomes for women, compared with men,” he said. “To this end, we have planned a chart-by-chart review, as well as a prospective analysis that will be performed in the currently enrolling NRG HN004 clinical trial.”
“The outcome of this study was very surprising to us, the idea that there are disparities in both the treatment that women receive relative to men, but also in the rate of death from head and neck cancer for women compared to men,” commented ASCO Expert Joshua Jones, MD, MA, who is also a radiation oncologist at the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia.
Dr. Katzel and his colleagues used the Kaiser Permanente Northern California registry to identify patients with stage II to IVB head and neck cancer diagnosed during 2000-2015.
Analyses were based on 223 women and 661 men, relative numbers that are not surprising given the known demographics of this cancer. Oropharyngeal tumors accounted for 38% of the cancers in the former, but 55% in the latter. (HPV status was not directly ascertained.)
The rate of receipt of intensive chemotherapy was 35% for women and 46% for men (adjusted odds ratio, 0.68; 95% CI, 0.48-0.98; P = .006). Similarly, the rate of receipt of radiation therapy was 60% for women and 70% for men (AOR, 0.79; 95% CI, 0.56-1.11; P = .008). Receipt of surgery was similar for the sexes.
The investigators analyzed deaths according to type using a GCE model that controlled for age, sex, tumor site, and Charlson Comorbidity Index. “The GCE model essentially describes the degree to which cancer is the patient’s problem,” Dr. Katzel explained.
Results showed that both women and men were more likely to die from cancer than from other causes; however, the ratio was 7 for women, compared with just 3.8 for men, a difference translating to a relative hazard ratio of 1.92 (95% CI, 1.07-3.43).
In terms of potential confounding, there were only 19 noncancer deaths among the women studied, suggesting that they may have been more healthy than the men, which could have influenced the calculations, according to Dr. Katzel.
“This GCE model has been validated in head and neck cancer, but also in breast cancer, prostate cancer, and endometrial cancer, so we are using a validated model to do this evaluation,” he noted. “So I would say we are confident in our findings.”
Dr. Katzel disclosed that he had no relevant conflicts of interest. The study received funding from Kaiser Permanente Northern California Graduate Medical Education Department.
SOURCE: Park A et al. ASCO 2018 Abstract LBA6002.
CHICAGO – Sex disparities in the treatment of head and neck cancer may be leading to poorer outcomes for women, according to a retrospective registry-based cohort study of 884 patients reported at annual meeting of the American Society of Clinical Oncology.
“The treatment of head and neck cancer often requires intensive treatment that can have lasting side effects,” senior study author Jed A. Katzel, MD, a medical oncologist at Kaiser Permanente in Santa Clara, Calif., said in a press briefing. “Our goal was to review data from a large group of patients in Northern California to determine which patients are most likely to benefit from aggressive therapy, while minimizing toxicity for those likely to die from competing events.”
The reasons for the observed sex disparities are not known, according to Dr. Katzel. However, they may include patient preferences, physician practices, and the higher proportion among men of oropharynx tumors, as those tumors are more commonly associated with human papillomavirus (HPV), which carries a more favorable prognosis.
“Further investigation is needed to determine if there is an actual difference in treatment and outcomes for women, compared with men,” he said. “To this end, we have planned a chart-by-chart review, as well as a prospective analysis that will be performed in the currently enrolling NRG HN004 clinical trial.”
“The outcome of this study was very surprising to us, the idea that there are disparities in both the treatment that women receive relative to men, but also in the rate of death from head and neck cancer for women compared to men,” commented ASCO Expert Joshua Jones, MD, MA, who is also a radiation oncologist at the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia.
Dr. Katzel and his colleagues used the Kaiser Permanente Northern California registry to identify patients with stage II to IVB head and neck cancer diagnosed during 2000-2015.
Analyses were based on 223 women and 661 men, relative numbers that are not surprising given the known demographics of this cancer. Oropharyngeal tumors accounted for 38% of the cancers in the former, but 55% in the latter. (HPV status was not directly ascertained.)
The rate of receipt of intensive chemotherapy was 35% for women and 46% for men (adjusted odds ratio, 0.68; 95% CI, 0.48-0.98; P = .006). Similarly, the rate of receipt of radiation therapy was 60% for women and 70% for men (AOR, 0.79; 95% CI, 0.56-1.11; P = .008). Receipt of surgery was similar for the sexes.
The investigators analyzed deaths according to type using a GCE model that controlled for age, sex, tumor site, and Charlson Comorbidity Index. “The GCE model essentially describes the degree to which cancer is the patient’s problem,” Dr. Katzel explained.
Results showed that both women and men were more likely to die from cancer than from other causes; however, the ratio was 7 for women, compared with just 3.8 for men, a difference translating to a relative hazard ratio of 1.92 (95% CI, 1.07-3.43).
In terms of potential confounding, there were only 19 noncancer deaths among the women studied, suggesting that they may have been more healthy than the men, which could have influenced the calculations, according to Dr. Katzel.
“This GCE model has been validated in head and neck cancer, but also in breast cancer, prostate cancer, and endometrial cancer, so we are using a validated model to do this evaluation,” he noted. “So I would say we are confident in our findings.”
Dr. Katzel disclosed that he had no relevant conflicts of interest. The study received funding from Kaiser Permanente Northern California Graduate Medical Education Department.
SOURCE: Park A et al. ASCO 2018 Abstract LBA6002.
REPORTING FROM ASCO 2018
Key clinical point: Women with head and neck cancer may be relatively undertreated and therefore are more likely to die from the disease.
Major finding: Compared with male counterparts, female patients had lower rates of receiving intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) and a higher ratio of cancer to noncancer mortality (adjusted relative hazard ratio, 1.92).
Study details: Retrospective, registry-based, cohort study of 884 patients with stage II to IVB H&N cancer diagnosed during 2000-2015.
Disclosures: Dr. Katzel disclosed that he had no relevant conflicts of interest. The study received funding from Kaiser Permanente Northern California Graduate Medical Education Department.
Source: Park A et al. ASCO 2018, Abstract LBA6002.
TAILORx marks major advance for precision medicine in breast cancer
CHICAGO – , sparing them adverse effects and preventing overtreatment, TAILORx trial results show.
The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.
The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”
The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.
Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.
The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.
Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”
In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).
Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).
“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”
An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.
Tailoring treatment: ‘not too much and not too little’
“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”
“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.
“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”
Study details
All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.
Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.
Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”
Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.
The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).
In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.
The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.
Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.
SOURCE: Sparano et al. ASCO 2018 Abstract LBA1
CHICAGO – , sparing them adverse effects and preventing overtreatment, TAILORx trial results show.
The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.
The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”
The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.
Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.
The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.
Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”
In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).
Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).
“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”
An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.
Tailoring treatment: ‘not too much and not too little’
“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”
“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.
“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”
Study details
All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.
Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.
Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”
Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.
The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).
In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.
The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.
Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.
SOURCE: Sparano et al. ASCO 2018 Abstract LBA1
CHICAGO – , sparing them adverse effects and preventing overtreatment, TAILORx trial results show.
The findings, which were reported in the plenary session at the annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine, mark a major advance in precision medicine.
The recurrence score is known to be prognostic and to be predictive of benefit from adding chemotherapy to endocrine therapy, Dr. Sparano said. “But there was a major gap: There was uncertain benefit for patients who had a midrange score, about two-thirds of all patients who are treated.”
The phase 3 TAILORx trial registered 10,273 women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer, making it the largest adjuvant breast cancer trial to date. Analyses focused on the 6,711 evaluable women with a midrange recurrence score (defined as 11 through 25 in the trial), who were randomized to receive endocrine therapy alone or adjuvant chemotherapy plus endocrine therapy, with a noninferiority design. Of note, contemporary drugs and regimens were used.
Results at a median follow-up of 7.5 years showed that the trial met its primary endpoint: The risk of invasive disease-free survival events (invasive disease recurrence, second primary cancer, or death) was not inferior for women given endocrine therapy alone compared with counterparts given chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26), Dr. Sparano reported.
The groups were also on par, with absolute differences of no more than 1% between rates, with respect to a variety of other efficacy outcomes: freedom from distant recurrence and any recurrence, and overall survival.
Findings were similar across most subgroups. But analyses suggested that women aged 50 years and younger having a recurrence score of 16-25 did fare better when they received chemotherapy. “Though exploratory from a statistical perspective, this is a highly clinically relevant observation,” he maintained. “It suggests ... that chemotherapy should be spared with caution in this subgroup, after a careful discussion of potential benefits and risks in a shared decision process.”
In other findings, analyses of the trial’s nonrandomized groups confirmed excellent outcomes among women with a low recurrence score (defined as 0-10) given endocrine therapy alone, and at the other end of the spectrum, need for a more aggressive approach, including chemotherapy, among women with a high recurrence score (defined as 26-100).
Ultimately, application of the recurrence score allowed 69% of the entire trial population to skip chemotherapy: all of those women with a score of 0-10 (16% of the trial population), those older than 50 years with a score of 11-25 (45%), and those aged 50 years or younger with a score of 11-15 (8%).
“Although this trial was designed in 2003, it was designed with the goal of addressing one of the themes at this 2018 meeting, expanding the reach of precision medicine,” Dr. Sparano pointed out. “It also embodies the core values of ASCO: By providing the highest level of evidence, it can have a direct and immediate impact on the care of our patients.”
An ongoing companion phase 3 trial, RxPONDER, is assessing the benefit of applying the recurrence score in women who are similar but instead have node-positive disease.
Tailoring treatment: ‘not too much and not too little’
“These are very important data because this is the most common form of breast cancer in the United States and other developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO Expert Harold Burstein, MD, PhD, FASCO. “The data provided here today from this massive NCI-sponsored trial show that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”
“This is not so much about de-escalation ... The goal of this study was not to just use less treatment, the goal was to tailor treatment – they chose the title very aptly, with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said Dr. Burstein, a medical oncologist at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.
“This is extraordinary data for breast cancer doctors and women who have breast cancer. It allows you to individualize treatment based on extraordinary science, which now has tremendous prospective validation,” he said. Overall, “women with breast cancer who are getting modern therapy are doing extraordinarily well, and this test shows us how to tailor that management so they get exactly the right amount of treatment – not too much and not too little.”
Study details
All of the women with hormone receptor–positive, HER2-negative, node-negative early-stage breast cancer enrolled in TAILORx met National Comprehensive Cancer Network guidelines for receiving adjuvant chemotherapy.
Roughly 69% had an intermediate recurrence score (11-25) and were randomized. All of the 17% having a low recurrence score (0-10) were given only endocrine therapy, and all of the 14% with a high recurrence score (26-100) were given both adjuvant chemotherapy and endocrine therapy.
Of note, the recurrence scores used to define midrange were adjusted downward from those conventionally used to account for exclusion of patients with higher-risk HER2-positive disease and to minimize potential for undertreatment, Dr. Sparano explained. “I think you will see changes in the near future as to how Genomic Health reports their results.”
Among the women with midrange scores who were randomized, the hazard ratio for invasive disease-free survival with endocrine therapy alone compared with chemotherapy plus endocrine therapy (1.08) fell well within the predefined hazard ratio for noninferiority (1.322). The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy and 84.3% with chemotherapy plus endocrine therapy.
The groups had similar rates of freedom from distant recurrence (94.5% vs. 95.0%; hazard ratio, 1.10; P = .48) and distant or locoregional recurrence (92.2% vs. 92.9%; hazard ratio, 1.11; P = .33), and similar overall survival (93.9% vs. 93.8%; hazard ratio for death, 0.99; P = .89).
In exploratory analyses, there was an interaction of age and recurrence score (P = .004) whereby women aged 50 or younger derived some benefit from chemotherapy if they had a recurrence score of 16-20 (9% fewer invasive disease–free survival events, including 2% fewer distant recurrences) or a recurrence score 21-25 (6% fewer invasive disease–free survival events, mainly distant recurrences). “This is information that could drive some younger women who have a recurrence score in this range to accept chemotherapy,” Dr. Sparano said.
The 9-year rate of distant recurrence averaged 5% among the women with midrange scores overall. It was just 3% among the women with a low recurrence score given endocrine therapy alone, but it was still 13% among the women with a high recurrence score despite receiving both endocrine therapy and chemotherapy. The last finding may “indicate the need to explore potentially more effective therapies in this setting,” he proposed.
Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with Metastat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.
SOURCE: Sparano et al. ASCO 2018 Abstract LBA1
REPORTING FROM ASCO 2018
Key clinical point: The majority of women with HR-positive, HER2-negative, node-negative early-stage breast cancer who have an intermediate recurrence score can safely skip adjuvant chemotherapy.
Major finding: Among women with an Oncotype DX Recurrence Score in the midrange (11-25), invasive disease–free survival with endocrine therapy alone was not inferior to that with chemotherapy plus endocrine therapy (hazard ratio, 1.08; P = .26).
Study details: A phase 3 trial among 10,273 women with HR-positive, HER2-negative, node-negative early-stage breast cancer, with a noninferiority randomized component among the 6,711 women with a midrange recurrence score (TAILORx trial).
Disclosures: Dr. Sparano disclosed that he has a consulting or advisory role with Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock or other ownership interests with MetaStat; and receives research funding (institutional) from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. This study received funding primarily from the National Cancer Institute, National Institutes of Health. Additional support was provided by the Breast Cancer Research Foundation, Komen Foundation, and U.S. Postal Service Breast Cancer Stamp.
Source: Sparano et al. ASCO 2018 Abstract LBA1.
Maintenance chemo boosts survival for youth with high-risk rhabdomyosarcoma
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
REPORTING FROM ASCO 2018
TAILORx: Most women with intermediate risk ER+ breast cancer can safely skip chemo
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
REPORTING FROM ASCO 2018
Atezolizumab has PFS benefit in first-line squamous NSCLC
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
REPORTING FROM ASCO 2018
Key clinical point: .
Major finding: Compared with chemotherapy alone, chemotherapy plus atezolizumab prolonged median progression-free survival from 5.6 to 6.3 months (hazard ratio, 0.71; P = .0001).
Study details: A phase 3 randomized, controlled trial among 1,021 all-comer (PD-L1–unselected), chemotherapy-naïve patients with stage IV squamous NSCLC (IMpower131 trial).
Disclosures: Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
Source: Jotte et al. ASCO 2018 Abstract LBA9000.
A blood test to detect lung cancer inches toward the clinic
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CHICAGO - Uptake of recommended low-dose CT for lung cancer screening has been dismal. Blood-based assays are an attractive alternative being explored by the Circulating Cell–Free Genome Atlas (CCGA) project. Interim results of a CCGA study of 561 individuals without cancer and 118 patients with lung cancers of all stages have found that a trio of assays searching for molecular signatures in plasma cell-free DNA achieved roughly 50% sensitivity for detection of early-stage (stage I-IIIA) lung cancers and 91% sensitivity for detection of late-stage (stage IIIB-IV) lung cancers.
In this video interview from the annual meeting of the American Society of Clinical Oncology, lead study author Geoffrey R. Oxnard, MD, of the Dana-Farber Cancer Institute, Boston, discusses the science behind these assays, how they may fill an unmet medical need, and ongoing work to bring them into the clinic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO - Uptake of recommended low-dose CT for lung cancer screening has been dismal. Blood-based assays are an attractive alternative being explored by the Circulating Cell–Free Genome Atlas (CCGA) project. Interim results of a CCGA study of 561 individuals without cancer and 118 patients with lung cancers of all stages have found that a trio of assays searching for molecular signatures in plasma cell-free DNA achieved roughly 50% sensitivity for detection of early-stage (stage I-IIIA) lung cancers and 91% sensitivity for detection of late-stage (stage IIIB-IV) lung cancers.
In this video interview from the annual meeting of the American Society of Clinical Oncology, lead study author Geoffrey R. Oxnard, MD, of the Dana-Farber Cancer Institute, Boston, discusses the science behind these assays, how they may fill an unmet medical need, and ongoing work to bring them into the clinic.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO - Uptake of recommended low-dose CT for lung cancer screening has been dismal. Blood-based assays are an attractive alternative being explored by the Circulating Cell–Free Genome Atlas (CCGA) project. Interim results of a CCGA study of 561 individuals without cancer and 118 patients with lung cancers of all stages have found that a trio of assays searching for molecular signatures in plasma cell-free DNA achieved roughly 50% sensitivity for detection of early-stage (stage I-IIIA) lung cancers and 91% sensitivity for detection of late-stage (stage IIIB-IV) lung cancers.
In this video interview from the annual meeting of the American Society of Clinical Oncology, lead study author Geoffrey R. Oxnard, MD, of the Dana-Farber Cancer Institute, Boston, discusses the science behind these assays, how they may fill an unmet medical need, and ongoing work to bring them into the clinic.
REPORTING FROM ASCO 2018
Metastatic colorectal cancer chemo costs double in Washington vs. British Columbia
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First-line systemic therapy for metastatic colorectal cancer costs twice as much in western Washington state as it does just across the border in British Columbia, Canada, but the more costly therapy does not net better survival, finds a cohort study reported at the annual meeting of the American Society of Clinical Oncology.
Differences between the United States and Canada in health care systems are well established, with a multipayer mix of private and public insurers in the former, and a single-payer, universal, public system in the latter, lead study author Todd Yezefski, MD, a senior fellow at the Fred Hutchinson Cancer Research Center in Seattle and the University of Washington School of Medicine, noted in a press briefing.
“Several studies have shown that overall health care utilization and costs in the U.S. are higher than in Canada. However, outcomes are generally similar, if not worse, in the U.S.,” he commented. “There have really been few studies, though, that have looked at treatment patterns, costs, and outcomes associated with a specific disease such as colorectal cancer.”
Results of the study of 2,197 patients with newly diagnosed metastatic colorectal cancer showed that the monthly cost for first-line systemic therapy exceeded $12,000 in western Washington state (excluding Medicare beneficiaries), compared with about $6,000 in British Columbia, even though the leading regimen in the latter region contained a targeted therapy. At the same time, median overall survival for patients given systemic therapy was essentially the same, approaching 2 years.
“Despite significantly higher costs, patients in western Washington didn’t do any better than those in British Columbia. Another way of saying this is they got the same bang for more buck,” Dr. Yezefski summarized. “Drug prices in Canada are generally set by the government. In the United States, we believe that if Medicare is allowed to negotiate drug prices with pharmaceutical companies, drug prices can be lower, and private insurers will oftentimes follow suit.”
In future work, the investigators plan to repeat analyses after including Medicare patients in the western Washington cohort (likely rendering the two groups more comparable) and to assess other aspects of health care utilization, such as total duration of chemotherapy, hospital use, radiation therapy, and surgery.
“The United States is probably the only country in the world where we actually have no real way of constraining the cost of health care. Certainly, that pertains to the cost of drugs,” commented Richard L. Schilsky, MD, FACP, FASCO, chief medical officer of ASCO and moderator of the press briefing. The U.S. Food and Drug Administration considers only the safety and efficacy of drugs when deciding whether they should be allowed on the market, he noted. “Once they are on the market, Medicare is generally required by law to pay for the cost of drugs, and the private insurers typically follow suit. So there really is no way to put any brakes on the system, which is not the case in most other health care systems in the world.” Other countries generally have a second agency or appointed body that performs some type of value assessment to determine whether the health care system can actually afford to offer the drug to the population. “That, of course, is a hypothesized reason for why, in Canada, you can get what would generally be considered a very expensive treatment regimen in the U.S. at half the cost of what it takes to deliver a similar regimen in the U.S. and still get equivalent outcomes,” Dr. Schilsky said.
For the study, Dr. Yezefski and colleagues identified patients with metastatic colorectal cancer newly diagnosed in 2010 or later in the regional database linking western Washington Surveillance, Epidemiology and End Results (SEER) data to claims from two large commercial insurers, and in the BC Cancer Agency database. Analyses were based on data from 575 patients in western Washington and 1,622 similar patients in British Columbia. Median age was 60 years in the former group and 66 years in the latter.
The rate of receipt of first-line systemic therapy was higher among the western Washington group than among the British Columbia group (79% vs. 68%, P less than.01), possibly because they were younger, Dr. Yezefski speculated. The most common regimen given to the former was FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) chemotherapy (39%), whereas the most common given to the latter was FOLFIRI (irinotecan, 5-fluorouracil, and folinic acid) chemotherapy with bevacizumab (Avastin) (32%).
The mean monthly per-patient cost of first-line systemic therapy was $12,345 in western Washington, roughly double the $6,195 in British Columbia (P less than .01). Mean lifetime monthly systemic therapy costs were also higher in the former region ($7,883 vs. $4,830, P less than .01). However, median overall survival between the two regions was essentially the same, both among patients who received systemic therapy (21.4 vs. 22.1 months) and among all patients (17.4 vs. 16.9 months). Dr. Yezefski disclosed that he had no relevant conflicts of interest.
The study received funding from the Fred Hutchinson Cancer Research Center and BC Cancer Agency.
SOURCE: Yezefski et al., abstract LBA3579, https://am.asco.org/abstracts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
First-line systemic therapy for metastatic colorectal cancer costs twice as much in western Washington state as it does just across the border in British Columbia, Canada, but the more costly therapy does not net better survival, finds a cohort study reported at the annual meeting of the American Society of Clinical Oncology.
Differences between the United States and Canada in health care systems are well established, with a multipayer mix of private and public insurers in the former, and a single-payer, universal, public system in the latter, lead study author Todd Yezefski, MD, a senior fellow at the Fred Hutchinson Cancer Research Center in Seattle and the University of Washington School of Medicine, noted in a press briefing.
“Several studies have shown that overall health care utilization and costs in the U.S. are higher than in Canada. However, outcomes are generally similar, if not worse, in the U.S.,” he commented. “There have really been few studies, though, that have looked at treatment patterns, costs, and outcomes associated with a specific disease such as colorectal cancer.”
Results of the study of 2,197 patients with newly diagnosed metastatic colorectal cancer showed that the monthly cost for first-line systemic therapy exceeded $12,000 in western Washington state (excluding Medicare beneficiaries), compared with about $6,000 in British Columbia, even though the leading regimen in the latter region contained a targeted therapy. At the same time, median overall survival for patients given systemic therapy was essentially the same, approaching 2 years.
“Despite significantly higher costs, patients in western Washington didn’t do any better than those in British Columbia. Another way of saying this is they got the same bang for more buck,” Dr. Yezefski summarized. “Drug prices in Canada are generally set by the government. In the United States, we believe that if Medicare is allowed to negotiate drug prices with pharmaceutical companies, drug prices can be lower, and private insurers will oftentimes follow suit.”
In future work, the investigators plan to repeat analyses after including Medicare patients in the western Washington cohort (likely rendering the two groups more comparable) and to assess other aspects of health care utilization, such as total duration of chemotherapy, hospital use, radiation therapy, and surgery.
“The United States is probably the only country in the world where we actually have no real way of constraining the cost of health care. Certainly, that pertains to the cost of drugs,” commented Richard L. Schilsky, MD, FACP, FASCO, chief medical officer of ASCO and moderator of the press briefing. The U.S. Food and Drug Administration considers only the safety and efficacy of drugs when deciding whether they should be allowed on the market, he noted. “Once they are on the market, Medicare is generally required by law to pay for the cost of drugs, and the private insurers typically follow suit. So there really is no way to put any brakes on the system, which is not the case in most other health care systems in the world.” Other countries generally have a second agency or appointed body that performs some type of value assessment to determine whether the health care system can actually afford to offer the drug to the population. “That, of course, is a hypothesized reason for why, in Canada, you can get what would generally be considered a very expensive treatment regimen in the U.S. at half the cost of what it takes to deliver a similar regimen in the U.S. and still get equivalent outcomes,” Dr. Schilsky said.
For the study, Dr. Yezefski and colleagues identified patients with metastatic colorectal cancer newly diagnosed in 2010 or later in the regional database linking western Washington Surveillance, Epidemiology and End Results (SEER) data to claims from two large commercial insurers, and in the BC Cancer Agency database. Analyses were based on data from 575 patients in western Washington and 1,622 similar patients in British Columbia. Median age was 60 years in the former group and 66 years in the latter.
The rate of receipt of first-line systemic therapy was higher among the western Washington group than among the British Columbia group (79% vs. 68%, P less than.01), possibly because they were younger, Dr. Yezefski speculated. The most common regimen given to the former was FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) chemotherapy (39%), whereas the most common given to the latter was FOLFIRI (irinotecan, 5-fluorouracil, and folinic acid) chemotherapy with bevacizumab (Avastin) (32%).
The mean monthly per-patient cost of first-line systemic therapy was $12,345 in western Washington, roughly double the $6,195 in British Columbia (P less than .01). Mean lifetime monthly systemic therapy costs were also higher in the former region ($7,883 vs. $4,830, P less than .01). However, median overall survival between the two regions was essentially the same, both among patients who received systemic therapy (21.4 vs. 22.1 months) and among all patients (17.4 vs. 16.9 months). Dr. Yezefski disclosed that he had no relevant conflicts of interest.
The study received funding from the Fred Hutchinson Cancer Research Center and BC Cancer Agency.
SOURCE: Yezefski et al., abstract LBA3579, https://am.asco.org/abstracts.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
First-line systemic therapy for metastatic colorectal cancer costs twice as much in western Washington state as it does just across the border in British Columbia, Canada, but the more costly therapy does not net better survival, finds a cohort study reported at the annual meeting of the American Society of Clinical Oncology.
Differences between the United States and Canada in health care systems are well established, with a multipayer mix of private and public insurers in the former, and a single-payer, universal, public system in the latter, lead study author Todd Yezefski, MD, a senior fellow at the Fred Hutchinson Cancer Research Center in Seattle and the University of Washington School of Medicine, noted in a press briefing.
“Several studies have shown that overall health care utilization and costs in the U.S. are higher than in Canada. However, outcomes are generally similar, if not worse, in the U.S.,” he commented. “There have really been few studies, though, that have looked at treatment patterns, costs, and outcomes associated with a specific disease such as colorectal cancer.”
Results of the study of 2,197 patients with newly diagnosed metastatic colorectal cancer showed that the monthly cost for first-line systemic therapy exceeded $12,000 in western Washington state (excluding Medicare beneficiaries), compared with about $6,000 in British Columbia, even though the leading regimen in the latter region contained a targeted therapy. At the same time, median overall survival for patients given systemic therapy was essentially the same, approaching 2 years.
“Despite significantly higher costs, patients in western Washington didn’t do any better than those in British Columbia. Another way of saying this is they got the same bang for more buck,” Dr. Yezefski summarized. “Drug prices in Canada are generally set by the government. In the United States, we believe that if Medicare is allowed to negotiate drug prices with pharmaceutical companies, drug prices can be lower, and private insurers will oftentimes follow suit.”
In future work, the investigators plan to repeat analyses after including Medicare patients in the western Washington cohort (likely rendering the two groups more comparable) and to assess other aspects of health care utilization, such as total duration of chemotherapy, hospital use, radiation therapy, and surgery.
“The United States is probably the only country in the world where we actually have no real way of constraining the cost of health care. Certainly, that pertains to the cost of drugs,” commented Richard L. Schilsky, MD, FACP, FASCO, chief medical officer of ASCO and moderator of the press briefing. The U.S. Food and Drug Administration considers only the safety and efficacy of drugs when deciding whether they should be allowed on the market, he noted. “Once they are on the market, Medicare is generally required by law to pay for the cost of drugs, and the private insurers typically follow suit. So there really is no way to put any brakes on the system, which is not the case in most other health care systems in the world.” Other countries generally have a second agency or appointed body that performs some type of value assessment to determine whether the health care system can actually afford to offer the drug to the population. “That, of course, is a hypothesized reason for why, in Canada, you can get what would generally be considered a very expensive treatment regimen in the U.S. at half the cost of what it takes to deliver a similar regimen in the U.S. and still get equivalent outcomes,” Dr. Schilsky said.
For the study, Dr. Yezefski and colleagues identified patients with metastatic colorectal cancer newly diagnosed in 2010 or later in the regional database linking western Washington Surveillance, Epidemiology and End Results (SEER) data to claims from two large commercial insurers, and in the BC Cancer Agency database. Analyses were based on data from 575 patients in western Washington and 1,622 similar patients in British Columbia. Median age was 60 years in the former group and 66 years in the latter.
The rate of receipt of first-line systemic therapy was higher among the western Washington group than among the British Columbia group (79% vs. 68%, P less than.01), possibly because they were younger, Dr. Yezefski speculated. The most common regimen given to the former was FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) chemotherapy (39%), whereas the most common given to the latter was FOLFIRI (irinotecan, 5-fluorouracil, and folinic acid) chemotherapy with bevacizumab (Avastin) (32%).
The mean monthly per-patient cost of first-line systemic therapy was $12,345 in western Washington, roughly double the $6,195 in British Columbia (P less than .01). Mean lifetime monthly systemic therapy costs were also higher in the former region ($7,883 vs. $4,830, P less than .01). However, median overall survival between the two regions was essentially the same, both among patients who received systemic therapy (21.4 vs. 22.1 months) and among all patients (17.4 vs. 16.9 months). Dr. Yezefski disclosed that he had no relevant conflicts of interest.
The study received funding from the Fred Hutchinson Cancer Research Center and BC Cancer Agency.
SOURCE: Yezefski et al., abstract LBA3579, https://am.asco.org/abstracts.
REPORTING FROM ASCO 2018
Key clinical point: The higher cost for metastatic CRC systemic therapy in the United States versus Canada does not translate to better survival.
Major finding: Monthly cost of first-line systemic therapy was $12,345 in western Washington vs. $6,195 in British Columbia (P less than .01), but median overall survival was statistically indistinguishable (21.4 vs. 22.1 months).
Study details: A cohort study of 2,197 patients with newly diagnosed metastatic CRC from a regional database linking western Washington SEER to claims from two large commercial insurers and from the BC (British Columbia) Cancer Agency database.
Disclosures: Dr. Yezefski disclosed that he had no relevant conflicts of interest. The study received funding from the Fred Hutchinson Cancer Research Center and the BC Cancer Agency.
Source: Yezefski et al. Abstract LBA3579.
Head and neck cancers: Women less commonly receive intensive chemo
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CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).
In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.
Dr. Katzel reported no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).
In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.
Dr. Katzel reported no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).
In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.
Dr. Katzel reported no financial disclosures.
REPORTING FROM ASCO 2018
CBT-I bests acupuncture for treating insomnia among cancer survivors
Cancer survivors who have trouble sleeping saw improvements with both cognitive-behavioral therapy designed specifically for insomnia (CBT-I) and acupuncture, according to results from the randomized, controlled CHOICE trial. But the former is more efficacious.
“Insomnia can have deleterious effects on quality of life and function, and occurs in up to 60% of cancer survivors,” lead study author Jun J. Mao, MD, chief of integrative medicine service at Memorial Sloan Kettering Cancer Center, New York, said in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology.
“CBT-I is a highly effective therapy and can be considered the gold standard of treatment,” he noted. However, this modality may be limited by poor adherence and nonresponse. Moreover, it is highly specialized and not currently available in many cancer centers or communities.
Functional imaging studies have shown that acupuncture can regulate brain regions involving cognition and emotion that are essential to sleep regulation, and clinical research has shown that it can improve pain- and hot flash–related sleep disturbances, according to Dr. Mao. About 73% of U.S. comprehensive cancer centers offer acupuncture for symptom management.
Main results of the CHOICE (Choosing Options for Insomnia in Cancer Effectively) trial showed that patients in both the CBT-I and acupuncture groups reduced their Insomnia Severity Index scores by more than one-half at the end of the 8-weeks treatment period, but the reduction was a statistically significant 2.6 points greater with CBT-I. Benefit of each treatment was still evident after 12 weeks.
Response rate was higher with CBT-I than with acupuncture only among patients having mild insomnia at baseline, and the two treatments yielded similar improvements in mental and physical quality of life.
“Among cancer patients with insomnia, we found that both acupuncture and CBT-I produced clinically meaningful and durable benefit, but overall, CBT-I is more effective in reducing insomnia severity,” Dr. Mao concluded. “Our hope is that by doing this type of research, we can help patients and clinicians pick the right kind of treatment and help them to manage their sleep. Our next step is to really examine for what type of patient treatment would be beneficial, and how to deliver this type of effective treatment to the broader community of cancer patients.”
Insomnia among cancer survivors is both prevalent and problematic, agreed ASCO President Bruce E. Johnson, MD, FASCO.
“The most common way we treat this is pharmacologically, with sleeping pills,” he noted. “This trial shows that two different methods using something other than medications can help people with sleep, and not only do they help people with sleep, but they improve their quality of life.
“We think this information will be helpful for clinicians who end up having to decide, and also, we would use this information to help decide about how the severity of the insomnia is going to influence the treatment,” maintained Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute in Boston, and a leader of the center’s lung cancer program.
Study details
The CHOICE trial did not have any restrictions on cancer type or stage; more than a half-dozen types were represented among the 160 patients enrolled, with breast cancer (31%) and prostate cancer (23%) accounting for the largest shares. The majority of patients were white (70%) and had moderate to severe insomnia (79%).
Patients were randomized to receive either acupuncture sessions (10 sessions, with points selected to treat insomnia plus comorbid symptoms such as fatigue and anxiety) or CBT-I (7 sessions), each over the course of 8 weeks.
Main results showed that at the end of treatment, the reduction in Insomnia Severity Index was 8.3 points with acupuncture and 10.9 points with CBT-I (P = .0007), Dr. Mao reported. Benefit of each treatment was sustained after 12 weeks.
In stratified analysis, the rate of response (defined as a greater than 8-point reduction) was higher with CBT-I than with acupuncture among patients with mild insomnia (Insomnia Severity Index of 8-14) (85% vs. 18%; P less than .0001), but not among patients with moderate or severe insomnia (Insomnia Severity Index of 15 or higher) (75% vs. 66%; P = .26).
The two treatments were similarly efficacious with respect to quality of life, assessed with the Patient-Reported Outcomes Measurement Information System over the entire course of the trial, for both the physical health component (P = .4) and the mental health component (P = .36).
Dr. Mao disclosed no relevant conflicts of interest. The study received funding from the Patient-Centered Outcomes Research Institute.
SOURCE: Mao JJ et al. ASCO 2018. Abstract 10001.
Cancer survivors who have trouble sleeping saw improvements with both cognitive-behavioral therapy designed specifically for insomnia (CBT-I) and acupuncture, according to results from the randomized, controlled CHOICE trial. But the former is more efficacious.
“Insomnia can have deleterious effects on quality of life and function, and occurs in up to 60% of cancer survivors,” lead study author Jun J. Mao, MD, chief of integrative medicine service at Memorial Sloan Kettering Cancer Center, New York, said in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology.
“CBT-I is a highly effective therapy and can be considered the gold standard of treatment,” he noted. However, this modality may be limited by poor adherence and nonresponse. Moreover, it is highly specialized and not currently available in many cancer centers or communities.
Functional imaging studies have shown that acupuncture can regulate brain regions involving cognition and emotion that are essential to sleep regulation, and clinical research has shown that it can improve pain- and hot flash–related sleep disturbances, according to Dr. Mao. About 73% of U.S. comprehensive cancer centers offer acupuncture for symptom management.
Main results of the CHOICE (Choosing Options for Insomnia in Cancer Effectively) trial showed that patients in both the CBT-I and acupuncture groups reduced their Insomnia Severity Index scores by more than one-half at the end of the 8-weeks treatment period, but the reduction was a statistically significant 2.6 points greater with CBT-I. Benefit of each treatment was still evident after 12 weeks.
Response rate was higher with CBT-I than with acupuncture only among patients having mild insomnia at baseline, and the two treatments yielded similar improvements in mental and physical quality of life.
“Among cancer patients with insomnia, we found that both acupuncture and CBT-I produced clinically meaningful and durable benefit, but overall, CBT-I is more effective in reducing insomnia severity,” Dr. Mao concluded. “Our hope is that by doing this type of research, we can help patients and clinicians pick the right kind of treatment and help them to manage their sleep. Our next step is to really examine for what type of patient treatment would be beneficial, and how to deliver this type of effective treatment to the broader community of cancer patients.”
Insomnia among cancer survivors is both prevalent and problematic, agreed ASCO President Bruce E. Johnson, MD, FASCO.
“The most common way we treat this is pharmacologically, with sleeping pills,” he noted. “This trial shows that two different methods using something other than medications can help people with sleep, and not only do they help people with sleep, but they improve their quality of life.
“We think this information will be helpful for clinicians who end up having to decide, and also, we would use this information to help decide about how the severity of the insomnia is going to influence the treatment,” maintained Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute in Boston, and a leader of the center’s lung cancer program.
Study details
The CHOICE trial did not have any restrictions on cancer type or stage; more than a half-dozen types were represented among the 160 patients enrolled, with breast cancer (31%) and prostate cancer (23%) accounting for the largest shares. The majority of patients were white (70%) and had moderate to severe insomnia (79%).
Patients were randomized to receive either acupuncture sessions (10 sessions, with points selected to treat insomnia plus comorbid symptoms such as fatigue and anxiety) or CBT-I (7 sessions), each over the course of 8 weeks.
Main results showed that at the end of treatment, the reduction in Insomnia Severity Index was 8.3 points with acupuncture and 10.9 points with CBT-I (P = .0007), Dr. Mao reported. Benefit of each treatment was sustained after 12 weeks.
In stratified analysis, the rate of response (defined as a greater than 8-point reduction) was higher with CBT-I than with acupuncture among patients with mild insomnia (Insomnia Severity Index of 8-14) (85% vs. 18%; P less than .0001), but not among patients with moderate or severe insomnia (Insomnia Severity Index of 15 or higher) (75% vs. 66%; P = .26).
The two treatments were similarly efficacious with respect to quality of life, assessed with the Patient-Reported Outcomes Measurement Information System over the entire course of the trial, for both the physical health component (P = .4) and the mental health component (P = .36).
Dr. Mao disclosed no relevant conflicts of interest. The study received funding from the Patient-Centered Outcomes Research Institute.
SOURCE: Mao JJ et al. ASCO 2018. Abstract 10001.
Cancer survivors who have trouble sleeping saw improvements with both cognitive-behavioral therapy designed specifically for insomnia (CBT-I) and acupuncture, according to results from the randomized, controlled CHOICE trial. But the former is more efficacious.
“Insomnia can have deleterious effects on quality of life and function, and occurs in up to 60% of cancer survivors,” lead study author Jun J. Mao, MD, chief of integrative medicine service at Memorial Sloan Kettering Cancer Center, New York, said in a press briefing held in advance of the annual meeting of the American Society of Clinical Oncology.
“CBT-I is a highly effective therapy and can be considered the gold standard of treatment,” he noted. However, this modality may be limited by poor adherence and nonresponse. Moreover, it is highly specialized and not currently available in many cancer centers or communities.
Functional imaging studies have shown that acupuncture can regulate brain regions involving cognition and emotion that are essential to sleep regulation, and clinical research has shown that it can improve pain- and hot flash–related sleep disturbances, according to Dr. Mao. About 73% of U.S. comprehensive cancer centers offer acupuncture for symptom management.
Main results of the CHOICE (Choosing Options for Insomnia in Cancer Effectively) trial showed that patients in both the CBT-I and acupuncture groups reduced their Insomnia Severity Index scores by more than one-half at the end of the 8-weeks treatment period, but the reduction was a statistically significant 2.6 points greater with CBT-I. Benefit of each treatment was still evident after 12 weeks.
Response rate was higher with CBT-I than with acupuncture only among patients having mild insomnia at baseline, and the two treatments yielded similar improvements in mental and physical quality of life.
“Among cancer patients with insomnia, we found that both acupuncture and CBT-I produced clinically meaningful and durable benefit, but overall, CBT-I is more effective in reducing insomnia severity,” Dr. Mao concluded. “Our hope is that by doing this type of research, we can help patients and clinicians pick the right kind of treatment and help them to manage their sleep. Our next step is to really examine for what type of patient treatment would be beneficial, and how to deliver this type of effective treatment to the broader community of cancer patients.”
Insomnia among cancer survivors is both prevalent and problematic, agreed ASCO President Bruce E. Johnson, MD, FASCO.
“The most common way we treat this is pharmacologically, with sleeping pills,” he noted. “This trial shows that two different methods using something other than medications can help people with sleep, and not only do they help people with sleep, but they improve their quality of life.
“We think this information will be helpful for clinicians who end up having to decide, and also, we would use this information to help decide about how the severity of the insomnia is going to influence the treatment,” maintained Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute in Boston, and a leader of the center’s lung cancer program.
Study details
The CHOICE trial did not have any restrictions on cancer type or stage; more than a half-dozen types were represented among the 160 patients enrolled, with breast cancer (31%) and prostate cancer (23%) accounting for the largest shares. The majority of patients were white (70%) and had moderate to severe insomnia (79%).
Patients were randomized to receive either acupuncture sessions (10 sessions, with points selected to treat insomnia plus comorbid symptoms such as fatigue and anxiety) or CBT-I (7 sessions), each over the course of 8 weeks.
Main results showed that at the end of treatment, the reduction in Insomnia Severity Index was 8.3 points with acupuncture and 10.9 points with CBT-I (P = .0007), Dr. Mao reported. Benefit of each treatment was sustained after 12 weeks.
In stratified analysis, the rate of response (defined as a greater than 8-point reduction) was higher with CBT-I than with acupuncture among patients with mild insomnia (Insomnia Severity Index of 8-14) (85% vs. 18%; P less than .0001), but not among patients with moderate or severe insomnia (Insomnia Severity Index of 15 or higher) (75% vs. 66%; P = .26).
The two treatments were similarly efficacious with respect to quality of life, assessed with the Patient-Reported Outcomes Measurement Information System over the entire course of the trial, for both the physical health component (P = .4) and the mental health component (P = .36).
Dr. Mao disclosed no relevant conflicts of interest. The study received funding from the Patient-Centered Outcomes Research Institute.
SOURCE: Mao JJ et al. ASCO 2018. Abstract 10001.
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: After 8 weeks of treatment, the reduction in Insomnia Severity Index was 8.3 points with acupuncture and 10.9 points with CBT-I (P = .0007).
Study details: A randomized, controlled trial among 160 survivors of diverse cancers having any degree of insomnia.
Disclosures: Dr. Mao disclosed no relevant conflicts of interest. The study received funding from the Patient-Centered Outcomes Research Institute.
Source: Mao JJ et al. ASCO 2018. Abstract 10001.