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Ketorolac may reduce breast cancer recurrence risk, particularly in overweight patients
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.
Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.
“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.
Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.
Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.
This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.
The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).
Further evaluation revealed that the benefit of ketorolac was “clearly associated” with a reduction in early metastases, both overall and in the high-BMI subgroup, the investigators said.
By contrast, intraoperative diclofenac was not associated with a decrease in distant recurrences, overall (adjusted HR, 1.04; 95% CI, 0.58-1.87, P = .88) or in BMI subgroup analysis, investigators said.
While some might be surprised that a single dose of ketorolac could reduce distant recurrence, it might be explained by the timing of NSAID delivery, they noted. In previous studies, primary tumor removal has been shown to disturb disease homeostasis, and thus might trigger early recurrences.
“Complex system dynamics are exquisitely sensitive on initial conditions, and, therefore, changes occurring in critical early times may be able to cause major changes in system evolution,” the investigators wrote in a discussion of the results.
The finding is also not without precedent. The authors cited one Scandinavian randomized trial in which a single course of perioperative cyclophosphamide significantly improved disease-free survival at more than 17 years of follow-up; by contrast, giving the treatment 2-4 weeks after mastectomy provided no such benefit.
In addition, ketorolac’s potential perioperative benefit has been shown in other tumor types, including improved disease-free survival in one institutional series of lung cancer patients, and reduced disease-specific mortality in a retrospective study of ovarian cancer patients.
The present breast cancer study is limited because it is retrospective, and does not address questions regarding optimal timing or duration of dose. However, “it suggests a potentially important repositioning of ketorolac in the intraoperative treatment of breast cancer patients with elevated BMI, and points to the need for a prospective confirmatory randomized trial,” the authors said.
Dr. Desmedt and her colleagues reported no conflicts of interest related to the study.
SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
FROM THE JOURNAL OF THE NATIONAL CANCER INSTITUTE
Key clinical point: Administration of ketorolac during primary tumor surgery was associated with a reduction of distant recurrences, particularly in overweight patients.
Major finding: Reduced recurrence was most evident in patients with high BMI (adjusted hazard ratio, 0.55; 95% CI, 0.31-0.96; P = .04).
Study details: Analysis of two retrospective series, including a total of 1,834 patients with breast cancer, evaluating intraoperative administration of ketorolac or diclofenac.
Disclosures: The authors declared no conflicts of interest.
Source: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.
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.
FDA advisory panelists reject Buvaya for acute pain
HYATTSVILLE, MD. – Two Food and Drug Administration advisory panels voted May 22 to reject buprenorphine sublingual spray for the treatment of moderate to severe postoperative pain.
At a joint meeting, advisers of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 18 to 1 not to recommend the spray for approval. The proposed trade name for the spray is Buvaya.
“I think that if this were a standard schedule II opioid with the efficacy profile of this drug, we probably would not be here,”stated Steven Meisel, PharmD, system director of medication safety at Fairview Health Services, Minneapolis. “We would not be here, because the efficacy [is] so weak compared to what is already out there. It just does not work for acute postoperative pain.”
According to INSYS Therapeutics, developer of the buprenorphine sublingual spray, opioid painkillers remain one of the best treatment options in managing moderate to severe pain despite the risk of addiction. The sublingual spray formulation also has a lower abuse potential, according to the company. This was corroborated in a briefing document of currently marketed buprenorphine products by the FDA.
Buprenorphine, an opioid partial agonist-antagonist, is a long-acting Schedule III opioid. The sublingual spray was developed as part of the Buprenorphine Sublingual Spray clinical development program, consisting of 10 studies including 7 phase 1 studies, a phase 2 open label study, and two phase 3 efficacy studies. The company’s application was based on the results of those two efficacy studies. Both phase 3 studies had similar designs, randomizing patients to receive varying doses of the sublingual spray. They also shared the primary endpoint of assessing postoperative pain using the Numeric Rating Scale (NRS) Summed Pain and Intensity Difference 48 hours (SPID-48) after surgery. The similarities continued with secondary endpoints, with both phase 3 studies looking at NRS-SPID scores at 4, 8, and 24 hours after surgery, NRS pain intensity difference (NRS PID) and score at each time point, and total pain relief (TOTPAR) at 4, 8, 24, and 48 hours after surgery. The only difference between the studies were the doses of sublingual buprenorphine administered to patients.
One of the phase 3 trials was discontinued when several patients because of sedation events at higher doses, but that trial still was used to guide the dose selection for the pivotal phase 3 study. In that study, 40 patients postoperative bunionectomy patients were randomized to receive placebo, 0.5 mg, or 1.0 mg of sublingual buprenorphine (SBS) three times daily (t.i.d.) or 1.0 mg of SBS twice a day (b.i.d.). The study demonstrated that all doses were superior to placebo in reducing pain based on reductions in NRS SPID-48 scores. In fact, the mean NRS SPID-48 scores were 260%, 216%, and 236% higher for the 0.5-mg t.i.d., 1.0-mg b.i.d., and 1.0-mg t.i.d. doses, respectively, compared with placebo, indicating a decrease in pain. The study also found that sublingual buprenorphine doses of greater than 0.5 mg were not more effective in treating postoperative pain.
The pivotal phase 3 efficacy study randomized 322 patients after bunionectomy into one of four treatment groups: placebo, 0.5 mg t.i.d., 0.25 mg t.i.d., or 0.125 mg t.i.d. Sublingual buprenorphine was much more effective in reducing pain and SPID-48 scores, compared with placebo. Patients taking placebo had SPID-48 scores of 93.40, compared with 135.84, 125.75, and 182.81 for the 0.125-mg, 0.25-mg, and 0.5-mg SBS groups, respectively.
The most common adverse events were nausea, vomiting, and hypoxia. Specifically, in the pivotal study, nausea was reported at all three doses of 0.125 mg, 0.25 mg, and 0.50 mg in 43.9%, 58.8%, and 83.3% of patients.
Anne-Michelle Ruha, MD, of the University of Arizona, Phoenix, cited the risk of hypoxia as her biggest concern. “There’s so many factors that we can’t predict, like undiagnosed sleep apnea,” she said. “We just don’t know when the respiratory depression worsens, so I’m uncomfortable with the high rate of hypoxia.”
Although not directly related to this application, INSYS had been the subject of an investigation by the federal government in regard to an illegal marketing scheme that provided incentives for doctors to prescribe Subsys, a powerful and highly addictive synthetic opioid. Documents recently have been unsealed in federal court that prompted the federal government to investigate INSYS. The company has addressed the previous allegations of wrongdoing and states that INSYS has become a “... new and better company in many important respects across the organization,” according to a statement.The FDA usually follows the recommendations of its advisory panels, but they are not binding.
HYATTSVILLE, MD. – Two Food and Drug Administration advisory panels voted May 22 to reject buprenorphine sublingual spray for the treatment of moderate to severe postoperative pain.
At a joint meeting, advisers of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 18 to 1 not to recommend the spray for approval. The proposed trade name for the spray is Buvaya.
“I think that if this were a standard schedule II opioid with the efficacy profile of this drug, we probably would not be here,”stated Steven Meisel, PharmD, system director of medication safety at Fairview Health Services, Minneapolis. “We would not be here, because the efficacy [is] so weak compared to what is already out there. It just does not work for acute postoperative pain.”
According to INSYS Therapeutics, developer of the buprenorphine sublingual spray, opioid painkillers remain one of the best treatment options in managing moderate to severe pain despite the risk of addiction. The sublingual spray formulation also has a lower abuse potential, according to the company. This was corroborated in a briefing document of currently marketed buprenorphine products by the FDA.
Buprenorphine, an opioid partial agonist-antagonist, is a long-acting Schedule III opioid. The sublingual spray was developed as part of the Buprenorphine Sublingual Spray clinical development program, consisting of 10 studies including 7 phase 1 studies, a phase 2 open label study, and two phase 3 efficacy studies. The company’s application was based on the results of those two efficacy studies. Both phase 3 studies had similar designs, randomizing patients to receive varying doses of the sublingual spray. They also shared the primary endpoint of assessing postoperative pain using the Numeric Rating Scale (NRS) Summed Pain and Intensity Difference 48 hours (SPID-48) after surgery. The similarities continued with secondary endpoints, with both phase 3 studies looking at NRS-SPID scores at 4, 8, and 24 hours after surgery, NRS pain intensity difference (NRS PID) and score at each time point, and total pain relief (TOTPAR) at 4, 8, 24, and 48 hours after surgery. The only difference between the studies were the doses of sublingual buprenorphine administered to patients.
One of the phase 3 trials was discontinued when several patients because of sedation events at higher doses, but that trial still was used to guide the dose selection for the pivotal phase 3 study. In that study, 40 patients postoperative bunionectomy patients were randomized to receive placebo, 0.5 mg, or 1.0 mg of sublingual buprenorphine (SBS) three times daily (t.i.d.) or 1.0 mg of SBS twice a day (b.i.d.). The study demonstrated that all doses were superior to placebo in reducing pain based on reductions in NRS SPID-48 scores. In fact, the mean NRS SPID-48 scores were 260%, 216%, and 236% higher for the 0.5-mg t.i.d., 1.0-mg b.i.d., and 1.0-mg t.i.d. doses, respectively, compared with placebo, indicating a decrease in pain. The study also found that sublingual buprenorphine doses of greater than 0.5 mg were not more effective in treating postoperative pain.
The pivotal phase 3 efficacy study randomized 322 patients after bunionectomy into one of four treatment groups: placebo, 0.5 mg t.i.d., 0.25 mg t.i.d., or 0.125 mg t.i.d. Sublingual buprenorphine was much more effective in reducing pain and SPID-48 scores, compared with placebo. Patients taking placebo had SPID-48 scores of 93.40, compared with 135.84, 125.75, and 182.81 for the 0.125-mg, 0.25-mg, and 0.5-mg SBS groups, respectively.
The most common adverse events were nausea, vomiting, and hypoxia. Specifically, in the pivotal study, nausea was reported at all three doses of 0.125 mg, 0.25 mg, and 0.50 mg in 43.9%, 58.8%, and 83.3% of patients.
Anne-Michelle Ruha, MD, of the University of Arizona, Phoenix, cited the risk of hypoxia as her biggest concern. “There’s so many factors that we can’t predict, like undiagnosed sleep apnea,” she said. “We just don’t know when the respiratory depression worsens, so I’m uncomfortable with the high rate of hypoxia.”
Although not directly related to this application, INSYS had been the subject of an investigation by the federal government in regard to an illegal marketing scheme that provided incentives for doctors to prescribe Subsys, a powerful and highly addictive synthetic opioid. Documents recently have been unsealed in federal court that prompted the federal government to investigate INSYS. The company has addressed the previous allegations of wrongdoing and states that INSYS has become a “... new and better company in many important respects across the organization,” according to a statement.The FDA usually follows the recommendations of its advisory panels, but they are not binding.
HYATTSVILLE, MD. – Two Food and Drug Administration advisory panels voted May 22 to reject buprenorphine sublingual spray for the treatment of moderate to severe postoperative pain.
At a joint meeting, advisers of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 18 to 1 not to recommend the spray for approval. The proposed trade name for the spray is Buvaya.
“I think that if this were a standard schedule II opioid with the efficacy profile of this drug, we probably would not be here,”stated Steven Meisel, PharmD, system director of medication safety at Fairview Health Services, Minneapolis. “We would not be here, because the efficacy [is] so weak compared to what is already out there. It just does not work for acute postoperative pain.”
According to INSYS Therapeutics, developer of the buprenorphine sublingual spray, opioid painkillers remain one of the best treatment options in managing moderate to severe pain despite the risk of addiction. The sublingual spray formulation also has a lower abuse potential, according to the company. This was corroborated in a briefing document of currently marketed buprenorphine products by the FDA.
Buprenorphine, an opioid partial agonist-antagonist, is a long-acting Schedule III opioid. The sublingual spray was developed as part of the Buprenorphine Sublingual Spray clinical development program, consisting of 10 studies including 7 phase 1 studies, a phase 2 open label study, and two phase 3 efficacy studies. The company’s application was based on the results of those two efficacy studies. Both phase 3 studies had similar designs, randomizing patients to receive varying doses of the sublingual spray. They also shared the primary endpoint of assessing postoperative pain using the Numeric Rating Scale (NRS) Summed Pain and Intensity Difference 48 hours (SPID-48) after surgery. The similarities continued with secondary endpoints, with both phase 3 studies looking at NRS-SPID scores at 4, 8, and 24 hours after surgery, NRS pain intensity difference (NRS PID) and score at each time point, and total pain relief (TOTPAR) at 4, 8, 24, and 48 hours after surgery. The only difference between the studies were the doses of sublingual buprenorphine administered to patients.
One of the phase 3 trials was discontinued when several patients because of sedation events at higher doses, but that trial still was used to guide the dose selection for the pivotal phase 3 study. In that study, 40 patients postoperative bunionectomy patients were randomized to receive placebo, 0.5 mg, or 1.0 mg of sublingual buprenorphine (SBS) three times daily (t.i.d.) or 1.0 mg of SBS twice a day (b.i.d.). The study demonstrated that all doses were superior to placebo in reducing pain based on reductions in NRS SPID-48 scores. In fact, the mean NRS SPID-48 scores were 260%, 216%, and 236% higher for the 0.5-mg t.i.d., 1.0-mg b.i.d., and 1.0-mg t.i.d. doses, respectively, compared with placebo, indicating a decrease in pain. The study also found that sublingual buprenorphine doses of greater than 0.5 mg were not more effective in treating postoperative pain.
The pivotal phase 3 efficacy study randomized 322 patients after bunionectomy into one of four treatment groups: placebo, 0.5 mg t.i.d., 0.25 mg t.i.d., or 0.125 mg t.i.d. Sublingual buprenorphine was much more effective in reducing pain and SPID-48 scores, compared with placebo. Patients taking placebo had SPID-48 scores of 93.40, compared with 135.84, 125.75, and 182.81 for the 0.125-mg, 0.25-mg, and 0.5-mg SBS groups, respectively.
The most common adverse events were nausea, vomiting, and hypoxia. Specifically, in the pivotal study, nausea was reported at all three doses of 0.125 mg, 0.25 mg, and 0.50 mg in 43.9%, 58.8%, and 83.3% of patients.
Anne-Michelle Ruha, MD, of the University of Arizona, Phoenix, cited the risk of hypoxia as her biggest concern. “There’s so many factors that we can’t predict, like undiagnosed sleep apnea,” she said. “We just don’t know when the respiratory depression worsens, so I’m uncomfortable with the high rate of hypoxia.”
Although not directly related to this application, INSYS had been the subject of an investigation by the federal government in regard to an illegal marketing scheme that provided incentives for doctors to prescribe Subsys, a powerful and highly addictive synthetic opioid. Documents recently have been unsealed in federal court that prompted the federal government to investigate INSYS. The company has addressed the previous allegations of wrongdoing and states that INSYS has become a “... new and better company in many important respects across the organization,” according to a statement.The FDA usually follows the recommendations of its advisory panels, but they are not binding.
New remote monitoring system lessens symptoms in head and neck cancer
A new system for remotely assessing and transmitting selected vitals and self-reported measures reduces symptom severity among patients with head and neck cancer receiving radiation therapy, in a randomized trial reported at a press briefing held before the annual meeting of the American Society of Clinical Oncology.
“Head and neck cancer patients who receive radiation treatment have a high symptom burden and also are at increased risk for dehydration during treatment,” said lead study author Susan K. Peterson, PhD, a professor in the department of behavioral science at the University of Texas MD Anderson Cancer Center, Houston. “Previously, we have shown that it was feasible to use mobile and sensor technology to identify treatment-related symptoms and early dehydration risk in patients receiving radiation treatment as part of their outpatient care.”
In the new trial, the investigators tested the CYCORE system (Cyberinfrastructure for Comparative Effectiveness Research), which consists of a Bluetooth-enabled weight scale and blood pressure cuff, and a mobile tablet with a symptom-tracking app that sends information directly to the physician each weekday. A network hub/router was set up in patients’ homes to transmit their sensor readouts, and the mobile app transmitted their symptom data to secure firewall-protected computers. “CYCORE also included a software infrastructure that enabled the analysis and viewing of data in near-real time and was compliant with safety and security and confidentiality standards,” Dr. Peterson noted.
Main trial results showed that compared with peers receiving only usual care (weekly visits with the radiation oncologist), patients receiving usual care augmented with the CYCORE system had lower mean scores on a 10-point scale for general symptoms (0.5-point difference) and for symptoms specific to head and neck cancer (0.6-point difference). In addition, daily remote tracking of patient well-being allowed clinicians to more rapidly detect and respond to symptoms.
“This is important because symptoms can affects patients’ ability to tolerate treatment and can also impact their quality of life during treatment,” Dr. Peterson said.
The mean age of the patients was 60 years; the oldest was 86 years old. “This supports the notion that the use of technology-based interventions can be feasible in older patients,” she maintained. In addition, patients in the CYCORE group showed at least 80% adherence to the daily monitoring tasks.
“We believe that good patient adherence plus the fact that this imposed minimal burden on clinicians for the monitoring supports the use of systems like CYCORE during intensive treatment periods in cancer care, and that using sensor and mobile technology to monitor patients during critical periods of outpatient care can provide a timely source of information for clinical decision making and may ultimately improve quality of life and health outcomes,” Dr. Peterson concluded. “Our next steps would be to explore ways to implement this as part of clinical care, including in community cancer centers, where most patients receive their care.”
“This is yet another application of technology-enabled sharing of information generated at home,” said ASCO President Bruce E. Johnson, MD, FASCO, noting that a similar study last year showed better patient-reported experience and overall survival.
Such technology will likely be increasingly used to obtain timely information that ultimately leads to a reduction in complications, he speculated.
“This information in head and neck cancer is particularly important because patients commonly get a lot of side effects when attempting to swallow enough fluids, such that some centers end up putting a feeding tube into the stomach because it’s so difficult to swallow,” added Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “So this is a particularly important clinical application in cancer.”
Study details
The trial population consisted of 357 patients undergoing radiation therapy for head and neck cancer. “We believe that this is the first and largest study of its kind in head and neck cancer,” Dr. Peterson said.
The severity of symptoms and their interference with daily activities were assessed at serial time points with the MD Anderson Symptom Inventory.
In the CYCORE group, 87% of patients measured their blood pressure daily, 86% measured their weight daily, and 80% used the symptom-tracking app daily.
At the end of radiation therapy, the CYCORE patients had lower (i.e., better) mean scores for general symptoms (e.g., pain, nausea, fatigue) relative to usual care counterparts (2.9 vs. 3.4), with a difference still evident 6-8 weeks later (1.6 vs. 1.9) (P = .007).
In addition, the CYCORE patients had lower mean scores for symptoms specific to head and neck cancer (e.g., dysphagia, pain, rash) at the end of radiation therapy (4.2 vs. 4.8), with a difference still evident 6-8 weeks later (1.7 vs. 2.1) (P = .009).
The groups fared essentially the same with respect to scores assessing interference of symptoms with activities of daily living.
Dr. Peterson disclosed that she had no relevant conflicts of interest. The study received funding from the National Institutes of Health.
SOURCE: Peterson et al. ASCO 2018, Abstract 6063.
A new system for remotely assessing and transmitting selected vitals and self-reported measures reduces symptom severity among patients with head and neck cancer receiving radiation therapy, in a randomized trial reported at a press briefing held before the annual meeting of the American Society of Clinical Oncology.
“Head and neck cancer patients who receive radiation treatment have a high symptom burden and also are at increased risk for dehydration during treatment,” said lead study author Susan K. Peterson, PhD, a professor in the department of behavioral science at the University of Texas MD Anderson Cancer Center, Houston. “Previously, we have shown that it was feasible to use mobile and sensor technology to identify treatment-related symptoms and early dehydration risk in patients receiving radiation treatment as part of their outpatient care.”
In the new trial, the investigators tested the CYCORE system (Cyberinfrastructure for Comparative Effectiveness Research), which consists of a Bluetooth-enabled weight scale and blood pressure cuff, and a mobile tablet with a symptom-tracking app that sends information directly to the physician each weekday. A network hub/router was set up in patients’ homes to transmit their sensor readouts, and the mobile app transmitted their symptom data to secure firewall-protected computers. “CYCORE also included a software infrastructure that enabled the analysis and viewing of data in near-real time and was compliant with safety and security and confidentiality standards,” Dr. Peterson noted.
Main trial results showed that compared with peers receiving only usual care (weekly visits with the radiation oncologist), patients receiving usual care augmented with the CYCORE system had lower mean scores on a 10-point scale for general symptoms (0.5-point difference) and for symptoms specific to head and neck cancer (0.6-point difference). In addition, daily remote tracking of patient well-being allowed clinicians to more rapidly detect and respond to symptoms.
“This is important because symptoms can affects patients’ ability to tolerate treatment and can also impact their quality of life during treatment,” Dr. Peterson said.
The mean age of the patients was 60 years; the oldest was 86 years old. “This supports the notion that the use of technology-based interventions can be feasible in older patients,” she maintained. In addition, patients in the CYCORE group showed at least 80% adherence to the daily monitoring tasks.
“We believe that good patient adherence plus the fact that this imposed minimal burden on clinicians for the monitoring supports the use of systems like CYCORE during intensive treatment periods in cancer care, and that using sensor and mobile technology to monitor patients during critical periods of outpatient care can provide a timely source of information for clinical decision making and may ultimately improve quality of life and health outcomes,” Dr. Peterson concluded. “Our next steps would be to explore ways to implement this as part of clinical care, including in community cancer centers, where most patients receive their care.”
“This is yet another application of technology-enabled sharing of information generated at home,” said ASCO President Bruce E. Johnson, MD, FASCO, noting that a similar study last year showed better patient-reported experience and overall survival.
Such technology will likely be increasingly used to obtain timely information that ultimately leads to a reduction in complications, he speculated.
“This information in head and neck cancer is particularly important because patients commonly get a lot of side effects when attempting to swallow enough fluids, such that some centers end up putting a feeding tube into the stomach because it’s so difficult to swallow,” added Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “So this is a particularly important clinical application in cancer.”
Study details
The trial population consisted of 357 patients undergoing radiation therapy for head and neck cancer. “We believe that this is the first and largest study of its kind in head and neck cancer,” Dr. Peterson said.
The severity of symptoms and their interference with daily activities were assessed at serial time points with the MD Anderson Symptom Inventory.
In the CYCORE group, 87% of patients measured their blood pressure daily, 86% measured their weight daily, and 80% used the symptom-tracking app daily.
At the end of radiation therapy, the CYCORE patients had lower (i.e., better) mean scores for general symptoms (e.g., pain, nausea, fatigue) relative to usual care counterparts (2.9 vs. 3.4), with a difference still evident 6-8 weeks later (1.6 vs. 1.9) (P = .007).
In addition, the CYCORE patients had lower mean scores for symptoms specific to head and neck cancer (e.g., dysphagia, pain, rash) at the end of radiation therapy (4.2 vs. 4.8), with a difference still evident 6-8 weeks later (1.7 vs. 2.1) (P = .009).
The groups fared essentially the same with respect to scores assessing interference of symptoms with activities of daily living.
Dr. Peterson disclosed that she had no relevant conflicts of interest. The study received funding from the National Institutes of Health.
SOURCE: Peterson et al. ASCO 2018, Abstract 6063.
A new system for remotely assessing and transmitting selected vitals and self-reported measures reduces symptom severity among patients with head and neck cancer receiving radiation therapy, in a randomized trial reported at a press briefing held before the annual meeting of the American Society of Clinical Oncology.
“Head and neck cancer patients who receive radiation treatment have a high symptom burden and also are at increased risk for dehydration during treatment,” said lead study author Susan K. Peterson, PhD, a professor in the department of behavioral science at the University of Texas MD Anderson Cancer Center, Houston. “Previously, we have shown that it was feasible to use mobile and sensor technology to identify treatment-related symptoms and early dehydration risk in patients receiving radiation treatment as part of their outpatient care.”
In the new trial, the investigators tested the CYCORE system (Cyberinfrastructure for Comparative Effectiveness Research), which consists of a Bluetooth-enabled weight scale and blood pressure cuff, and a mobile tablet with a symptom-tracking app that sends information directly to the physician each weekday. A network hub/router was set up in patients’ homes to transmit their sensor readouts, and the mobile app transmitted their symptom data to secure firewall-protected computers. “CYCORE also included a software infrastructure that enabled the analysis and viewing of data in near-real time and was compliant with safety and security and confidentiality standards,” Dr. Peterson noted.
Main trial results showed that compared with peers receiving only usual care (weekly visits with the radiation oncologist), patients receiving usual care augmented with the CYCORE system had lower mean scores on a 10-point scale for general symptoms (0.5-point difference) and for symptoms specific to head and neck cancer (0.6-point difference). In addition, daily remote tracking of patient well-being allowed clinicians to more rapidly detect and respond to symptoms.
“This is important because symptoms can affects patients’ ability to tolerate treatment and can also impact their quality of life during treatment,” Dr. Peterson said.
The mean age of the patients was 60 years; the oldest was 86 years old. “This supports the notion that the use of technology-based interventions can be feasible in older patients,” she maintained. In addition, patients in the CYCORE group showed at least 80% adherence to the daily monitoring tasks.
“We believe that good patient adherence plus the fact that this imposed minimal burden on clinicians for the monitoring supports the use of systems like CYCORE during intensive treatment periods in cancer care, and that using sensor and mobile technology to monitor patients during critical periods of outpatient care can provide a timely source of information for clinical decision making and may ultimately improve quality of life and health outcomes,” Dr. Peterson concluded. “Our next steps would be to explore ways to implement this as part of clinical care, including in community cancer centers, where most patients receive their care.”
“This is yet another application of technology-enabled sharing of information generated at home,” said ASCO President Bruce E. Johnson, MD, FASCO, noting that a similar study last year showed better patient-reported experience and overall survival.
Such technology will likely be increasingly used to obtain timely information that ultimately leads to a reduction in complications, he speculated.
“This information in head and neck cancer is particularly important because patients commonly get a lot of side effects when attempting to swallow enough fluids, such that some centers end up putting a feeding tube into the stomach because it’s so difficult to swallow,” added Dr. Johnson, who is also a professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “So this is a particularly important clinical application in cancer.”
Study details
The trial population consisted of 357 patients undergoing radiation therapy for head and neck cancer. “We believe that this is the first and largest study of its kind in head and neck cancer,” Dr. Peterson said.
The severity of symptoms and their interference with daily activities were assessed at serial time points with the MD Anderson Symptom Inventory.
In the CYCORE group, 87% of patients measured their blood pressure daily, 86% measured their weight daily, and 80% used the symptom-tracking app daily.
At the end of radiation therapy, the CYCORE patients had lower (i.e., better) mean scores for general symptoms (e.g., pain, nausea, fatigue) relative to usual care counterparts (2.9 vs. 3.4), with a difference still evident 6-8 weeks later (1.6 vs. 1.9) (P = .007).
In addition, the CYCORE patients had lower mean scores for symptoms specific to head and neck cancer (e.g., dysphagia, pain, rash) at the end of radiation therapy (4.2 vs. 4.8), with a difference still evident 6-8 weeks later (1.7 vs. 2.1) (P = .009).
The groups fared essentially the same with respect to scores assessing interference of symptoms with activities of daily living.
Dr. Peterson disclosed that she had no relevant conflicts of interest. The study received funding from the National Institutes of Health.
SOURCE: Peterson et al. ASCO 2018, Abstract 6063.
REPORTING FROM ASCO 2018
Key clinical point: .
Major finding: Compared with usual care, the system for tracking and transmitting vitals and self-reported measures through sensor and mobile devices was associated with milder general symptoms (0.5-point difference) and head and neck cancer symptoms (0.6-point difference).
Study details: A randomized controlled trial among 357 patients with head and neck cancer undergoing radiation therapy.
Disclosures: Dr. Peterson disclosed that she had no conflicts of interest. The study received funding from the National Institutes of Health.
Source: Peterson et al. ASCO 2018, Abstract 6063.
CRC recurrence surveillance studies: No benefit to high-intensity strategy
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
Clinical practice guidelines should be reevaluated in light of the findings of these two studies, according to Hanna K. Sanoff, MD.
While the studies both have methodological limitations, the need to revisit recommendations is important given the potential harms associated with more frequent testing, Dr. Sanoff said in an accompanying editorial.
“Because of their designs, results of the COLOFOL trial and the NCDB study should not be considered precise estimates of the effect of surveillance on survival,” she wrote. “However, as gold standard randomized controlled trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports.”
Both studies found that a high-intensity surveillance strategy offered no significant differences in key outcomes versus a low-intensity strategy. However, the NCDB study was a retrospective cohort analysis, so the results should be viewed in light of the inherent limitations of that study approach.
Similarly, although the COLOFOL study is randomized, it should be viewed as a pragmatic study, according to Dr. Sanoff, since investigators made several practical design decisions to ensure that patients would be enrolled and the study completed. For example, the eligibility criteria were not stringent with regard to confirming metastatic disease at entry.
Even so, the results of the trial are corroborated by another pragmatic randomized controlled trial, the Follow-up After Colorectal Surgery (FACS) study, which also showed no benefit to more frequent testing.
“There is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way,” Dr. Sanoff said in her editorial.
Hanna K. Sanoff, MD, is with the division of hematology/oncology at the University of North Carolina at Chapel Hill. These comments are derived from her editorial in JAMA Oncology. Dr. Sanoff reported no conflicts of interest relevant to her work on the editorial.
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
More frequent follow-up with computed tomography of the thorax and abdomen and serum carcinoembyronic antigen (CEA) testing does not significantly improve mortality rates or improve time to detection of recurrence, results of two studies published in JAMA have suggested.*
In COLOFOL, a randomized clinical trial including more than 2,500 patients with stage II or III colorectal cancer, more frequent follow-up with CT of the thorax and abdomen and serum CEA did not significantly improve 5-year overall mortality or colorectal cancer–specific mortality rates.
In the second study, a retrospective cohort analysis of the National Cancer Database (NCDB) including more than 8,500 patients with stage I-III colorectal cancer, investigators found no significant association between the surveillance testing frequency and time to detection of disease recurrence.
Taken together, these findings suggest a need to revisit clinical practice guidelines, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill said in a related editorial (for details, see “Views on the News”).
The COLOFOL randomized trial, reported by Henrik T. Sørensen, DMSc, head of the department of clinical epidemiology at Aarhus (Denmark) University Hospital, and his colleagues, included 2,509 patients with stage II or III colorectal cancer.
“The question of appropriate follow-up intervals has been controversial, and varying intensity of follow-up has been used within and among countries,” Dr. Sørensen and his coauthors said.
Patients were randomized either to a high-frequency group, in which CT and CEA testing were conducted at 6, 12, 18, 24, and 36 months after surgery, or to a low-frequency group that received testing only at 12 and 36 months after surgery.
Results of COLOFOL showed that the 5-year colorectal cancer–specific mortality rate was similar: 10.6% for the high-frequency follow-up group versus 11.4% for the low frequency group (risk difference, 0.8%; 95%confidence interval, –1.7% to 3.3%; P = .52).
Likewise, 5-year overall mortality was 13.0% for the high-frequency group and 14.1% for the low-frequency follow-up groups (risk difference, 1.1%; 95% CI, –1.6% to 3.8%; P = .43
High-intensity testing did result in recurrences being detected earlier; nevertheless, this did not translate into a reduced mortality rate, investigators said.
The retrospective NCDB analysis, reported by George J. Chang, MD, of University of Texas MD Anderson Cancer Center, Houston, and his coauthors, included 8,529 patients with stage I-III colorectal cancer treated at 1,175 facilities.
Facilities designated as high intensity for imaging performed a mean of 2.87 imaging tests over 3 years, compared with 1.63 for facilities designated as low intensity. Median time to detection of recurrence was similar between arms, at 15.1 months for patients treated at centers with high-intensity surveillance versus 16.0 months for those treated at low-intensity surveillance centers (hazard ratio, 0.99; 95% CI, 0.90-1.09).
High-intensity CEA testing facilities performed a mean of 4.31 tests within 3 years versus 1.63 for low-intensity facilities. Again, investigators found similar median time to detection of recurrence for high- and low-intensity facilities (15.9 months versus 15.3 months, respectively; hazard ratio, 1.00; 95% CI, 0.90-1.11)
Previously, the Follow-up After Colorectal Surgery (FACS) study, a randomized controlled trial, showed no survival benefit to more frequent testing, Dr. Chang and his colleagues noted.
“Based on these data and the recent FACS trial, current National Comprehensive Cancer Network (NCCN) guideline recommendations could be considered overtesting given the absence of improvement in recurrence detection or survival,” they wrote, noting that the NCCN guidelines have suggested CT testing every 6 months for 3 years.
Disclosures for the COLOFOL trial included one investigator who reported potential conflicts of interest with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a potential conflict of interest related to Johnson & Johnson. No other disclosures were reported.
SOURCES: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi; 10.1001/jama.2018.5816.
Correction, 6/8/18: An earlier version of this article misstated the name of the journal in which this study was published.
FROM JAMA
Key clinical point: In a randomized study, more frequent follow-up with CT of the thorax and abdomen and serum carcinoembryonic antigen (CEA) did not significantly improve mortality rates. In a retrospective study, there was no association found between frequency of testing and time to detection of recurrence.
Major finding: In the randomized trial, the 5-year colorectal cancer–specific mortality rate was 10.6% for high-frequency follow-up versus 11.4% for low frequency (risk difference, 0.8%; 95% confidence interval, –1.7% to 3.3%; P = .52). In the retrospective study, the median time to detection of recurrence was 15.1 months versus 16.0 months, respectively, for patients treated at centers with high- or low-intensity imaging surveillance (difference, –0.95 months; 95% CI, –2.59 to 0.68; hazard ratio, 0.99), with similar results for high- versus low-intensity CEA testing.
Study details: The COLOFOL randomized clinical trial, which included 2,509 patients with stage II or III colorectal cancer, and a retrospective cohort study of the National Cancer Database (NCDB), which included 8,529 patients with stage I-III colorectal cancer.
Disclosures: For the COLOFOL trial, one investigator reported disclosures with Janssen-Cilag and Merck Serono. For the NCDB study, one coauthor reported a disclosure related to Johnson & Johnson. No other disclosures were reported.
Source: Sørensen HT et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5623; Chang GJ et al. JAMA Oncol. 2018 May 22. doi: 10.1001/jama.2018.5816.
Palliative care may reduce suicide among lung cancer patients
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
FROM ATS 2018
Upfront NGS testing of metastatic NSCLC saves money, time
Comprehensive testing of newly diagnosed metastatic non–small cell lung cancer (NSCLC) with next-generation sequencing (NGS) for known lung cancer–related genomic alterations is cost-saving relative to single-gene testing strategies and often faster, a new study finds.
“We know now that genomic testing for all patients with advanced NSCLC is the standard of care to help detect oncogenic drivers, to inform treatment decisions,” lead study author Nathan A. Pennell, MD, PhD, codirector of the Cleveland Clinic lung cancer program, said in a press briefing leading up to the ASCO annual meeting. But the optimal strategy for this testing is unclear.
He and his colleagues conducted a decision analytic modeling study among hypothetical insurance plans having 1 million enrollees. Outcomes were compared between NGS testing and three single-gene testing strategies.
Data indicated that compared with exclusionary, sequential, or hot-spot panel testing approaches, NGS testing simultaneously for eight genomic alterations having Food and Drug Administration–approved or investigational targeted therapies could save up to $2.1 million among Medicare beneficiaries and up to $250,842 among patients covered by commercial insurance. The costs to payers decreased as the percentage of patients receiving NGS testing increased. Moreover, the wait time for results was similar or roughly half as long with NGS.
“Our results showed that there were substantial cost savings associated with upfront NGS testing compared to all other strategies,” Dr. Pennell said. “In addition, NGS had a faster turnaround time than either sequential or exclusionary testing, which is critically important for sick lung cancer patients, to make sure they get their treatment as quickly as possible. Waiting a month or longer is simply no longer viable for patients because they get sick very quickly and these treatments work very well.”
Of note, the model indicated that some patients undergoing initial single-gene testing strategies never had their genomic alterations detected because tissue for testing ran out and they were too sick to undergo another biopsy.
“The bottom line is, ultimately, using the best single test upfront results in the fastest turnaround time, the highest percentage of patients with targetable alterations identified, and overall the lowest cost to payers,” he summarized.
A major challenge in this population is going back and retesting for known or new genomic alterations, agreed ASCO President Bruce E. Johnson, MD, FASCO. “At our upcoming meeting, we are going to hear about RET, which may end up as a target and may therefore need to be tested for.”
Recently, oncologists have a new attractive option of billing for NGS panels rather than for single gene tests, he noted.
“This study really shows that by doing all the testing at the same time, you can both get results back more quickly as well as get information,” said Dr. Johnson, professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “This study looked at an NGS panel of eight genes, but most of the NGS panels contain somewhere between 50 and 400 genes, so you get a lot more information with this at a cost that’s competitive or less. So this will be welcome news to people who are ordering these gene panels.”
Study details
For NSCLC, there are currently approved treatments that target alterations in EGFR, ALK, ROS1, and BRAF, and investigational treatments in clinical trials that target alterations in MET, HER2, RET, and NTRK1.
In the model Dr. Pennell and his colleagues developed, patients with newly diagnosed metastatic NSCLC received testing for programmed death ligand 1 (PD-L1) plus testing for the above known lung cancer–related genes using one of four strategies:
- NGS testing (testing of all eight genes plus KRAS simultaneously).
- Sequential testing (testing one gene at a time starting with EGFR).
- Exclusionary testing (testing for KRAS mutation, the most common genomic alteration, followed by sequential testing for changes in other genes only if KRAS was not mutated).
- Hot-spot panel testing (combined testing for EGFR, ALK, ROS1, and BRAF), followed by either single-gene or NGS testing for alterations in other genes.
Model results indicated that among 1 million hypothetical plan enrollees, 2,066 patients covered by the Centers for Medicare & Medicaid Services and 156 covered by U.S. commercial insurers would have newly diagnosed metastatic NSCLC and therefore be eligible for testing.
Estimated time to receive test results was 2 weeks for NGS testing and for panel testing, compared with 4.7 weeks for exclusionary testing and 4.8 weeks for sequential testing.
In the CMS population, NGS testing would save about $1.4 million compared with exclusionary testing, more than $1.5 million compared with sequential testing, and about $2.1 million compared with panel testing. In the commercial health plan cohort, NGS would save $3,809 compared with exclusionary testing, $127,402 compared with sequential testing, and $250,842 compared with panel testing.
Dr. Pennell disclosed that he has a consulting or advisory role with AstraZeneca, Lilly, and Regeneron, and that his institution receives research funding from Genentech, NewLink Genetics, Clovis Oncology, Astex Pharmaceuticals, Celgene, AstraZeneca, Pfizer, and Merck. The study received funding from Novartis.
SOURCE: Pennell et al., ASCO Annual Meeting Abstract 9031.
Comprehensive testing of newly diagnosed metastatic non–small cell lung cancer (NSCLC) with next-generation sequencing (NGS) for known lung cancer–related genomic alterations is cost-saving relative to single-gene testing strategies and often faster, a new study finds.
“We know now that genomic testing for all patients with advanced NSCLC is the standard of care to help detect oncogenic drivers, to inform treatment decisions,” lead study author Nathan A. Pennell, MD, PhD, codirector of the Cleveland Clinic lung cancer program, said in a press briefing leading up to the ASCO annual meeting. But the optimal strategy for this testing is unclear.
He and his colleagues conducted a decision analytic modeling study among hypothetical insurance plans having 1 million enrollees. Outcomes were compared between NGS testing and three single-gene testing strategies.
Data indicated that compared with exclusionary, sequential, or hot-spot panel testing approaches, NGS testing simultaneously for eight genomic alterations having Food and Drug Administration–approved or investigational targeted therapies could save up to $2.1 million among Medicare beneficiaries and up to $250,842 among patients covered by commercial insurance. The costs to payers decreased as the percentage of patients receiving NGS testing increased. Moreover, the wait time for results was similar or roughly half as long with NGS.
“Our results showed that there were substantial cost savings associated with upfront NGS testing compared to all other strategies,” Dr. Pennell said. “In addition, NGS had a faster turnaround time than either sequential or exclusionary testing, which is critically important for sick lung cancer patients, to make sure they get their treatment as quickly as possible. Waiting a month or longer is simply no longer viable for patients because they get sick very quickly and these treatments work very well.”
Of note, the model indicated that some patients undergoing initial single-gene testing strategies never had their genomic alterations detected because tissue for testing ran out and they were too sick to undergo another biopsy.
“The bottom line is, ultimately, using the best single test upfront results in the fastest turnaround time, the highest percentage of patients with targetable alterations identified, and overall the lowest cost to payers,” he summarized.
A major challenge in this population is going back and retesting for known or new genomic alterations, agreed ASCO President Bruce E. Johnson, MD, FASCO. “At our upcoming meeting, we are going to hear about RET, which may end up as a target and may therefore need to be tested for.”
Recently, oncologists have a new attractive option of billing for NGS panels rather than for single gene tests, he noted.
“This study really shows that by doing all the testing at the same time, you can both get results back more quickly as well as get information,” said Dr. Johnson, professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “This study looked at an NGS panel of eight genes, but most of the NGS panels contain somewhere between 50 and 400 genes, so you get a lot more information with this at a cost that’s competitive or less. So this will be welcome news to people who are ordering these gene panels.”
Study details
For NSCLC, there are currently approved treatments that target alterations in EGFR, ALK, ROS1, and BRAF, and investigational treatments in clinical trials that target alterations in MET, HER2, RET, and NTRK1.
In the model Dr. Pennell and his colleagues developed, patients with newly diagnosed metastatic NSCLC received testing for programmed death ligand 1 (PD-L1) plus testing for the above known lung cancer–related genes using one of four strategies:
- NGS testing (testing of all eight genes plus KRAS simultaneously).
- Sequential testing (testing one gene at a time starting with EGFR).
- Exclusionary testing (testing for KRAS mutation, the most common genomic alteration, followed by sequential testing for changes in other genes only if KRAS was not mutated).
- Hot-spot panel testing (combined testing for EGFR, ALK, ROS1, and BRAF), followed by either single-gene or NGS testing for alterations in other genes.
Model results indicated that among 1 million hypothetical plan enrollees, 2,066 patients covered by the Centers for Medicare & Medicaid Services and 156 covered by U.S. commercial insurers would have newly diagnosed metastatic NSCLC and therefore be eligible for testing.
Estimated time to receive test results was 2 weeks for NGS testing and for panel testing, compared with 4.7 weeks for exclusionary testing and 4.8 weeks for sequential testing.
In the CMS population, NGS testing would save about $1.4 million compared with exclusionary testing, more than $1.5 million compared with sequential testing, and about $2.1 million compared with panel testing. In the commercial health plan cohort, NGS would save $3,809 compared with exclusionary testing, $127,402 compared with sequential testing, and $250,842 compared with panel testing.
Dr. Pennell disclosed that he has a consulting or advisory role with AstraZeneca, Lilly, and Regeneron, and that his institution receives research funding from Genentech, NewLink Genetics, Clovis Oncology, Astex Pharmaceuticals, Celgene, AstraZeneca, Pfizer, and Merck. The study received funding from Novartis.
SOURCE: Pennell et al., ASCO Annual Meeting Abstract 9031.
Comprehensive testing of newly diagnosed metastatic non–small cell lung cancer (NSCLC) with next-generation sequencing (NGS) for known lung cancer–related genomic alterations is cost-saving relative to single-gene testing strategies and often faster, a new study finds.
“We know now that genomic testing for all patients with advanced NSCLC is the standard of care to help detect oncogenic drivers, to inform treatment decisions,” lead study author Nathan A. Pennell, MD, PhD, codirector of the Cleveland Clinic lung cancer program, said in a press briefing leading up to the ASCO annual meeting. But the optimal strategy for this testing is unclear.
He and his colleagues conducted a decision analytic modeling study among hypothetical insurance plans having 1 million enrollees. Outcomes were compared between NGS testing and three single-gene testing strategies.
Data indicated that compared with exclusionary, sequential, or hot-spot panel testing approaches, NGS testing simultaneously for eight genomic alterations having Food and Drug Administration–approved or investigational targeted therapies could save up to $2.1 million among Medicare beneficiaries and up to $250,842 among patients covered by commercial insurance. The costs to payers decreased as the percentage of patients receiving NGS testing increased. Moreover, the wait time for results was similar or roughly half as long with NGS.
“Our results showed that there were substantial cost savings associated with upfront NGS testing compared to all other strategies,” Dr. Pennell said. “In addition, NGS had a faster turnaround time than either sequential or exclusionary testing, which is critically important for sick lung cancer patients, to make sure they get their treatment as quickly as possible. Waiting a month or longer is simply no longer viable for patients because they get sick very quickly and these treatments work very well.”
Of note, the model indicated that some patients undergoing initial single-gene testing strategies never had their genomic alterations detected because tissue for testing ran out and they were too sick to undergo another biopsy.
“The bottom line is, ultimately, using the best single test upfront results in the fastest turnaround time, the highest percentage of patients with targetable alterations identified, and overall the lowest cost to payers,” he summarized.
A major challenge in this population is going back and retesting for known or new genomic alterations, agreed ASCO President Bruce E. Johnson, MD, FASCO. “At our upcoming meeting, we are going to hear about RET, which may end up as a target and may therefore need to be tested for.”
Recently, oncologists have a new attractive option of billing for NGS panels rather than for single gene tests, he noted.
“This study really shows that by doing all the testing at the same time, you can both get results back more quickly as well as get information,” said Dr. Johnson, professor of medicine at the Dana-Farber Cancer Institute and a leader of the Dana-Farber/Harvard Cancer Center Lung Cancer Program, Boston. “This study looked at an NGS panel of eight genes, but most of the NGS panels contain somewhere between 50 and 400 genes, so you get a lot more information with this at a cost that’s competitive or less. So this will be welcome news to people who are ordering these gene panels.”
Study details
For NSCLC, there are currently approved treatments that target alterations in EGFR, ALK, ROS1, and BRAF, and investigational treatments in clinical trials that target alterations in MET, HER2, RET, and NTRK1.
In the model Dr. Pennell and his colleagues developed, patients with newly diagnosed metastatic NSCLC received testing for programmed death ligand 1 (PD-L1) plus testing for the above known lung cancer–related genes using one of four strategies:
- NGS testing (testing of all eight genes plus KRAS simultaneously).
- Sequential testing (testing one gene at a time starting with EGFR).
- Exclusionary testing (testing for KRAS mutation, the most common genomic alteration, followed by sequential testing for changes in other genes only if KRAS was not mutated).
- Hot-spot panel testing (combined testing for EGFR, ALK, ROS1, and BRAF), followed by either single-gene or NGS testing for alterations in other genes.
Model results indicated that among 1 million hypothetical plan enrollees, 2,066 patients covered by the Centers for Medicare & Medicaid Services and 156 covered by U.S. commercial insurers would have newly diagnosed metastatic NSCLC and therefore be eligible for testing.
Estimated time to receive test results was 2 weeks for NGS testing and for panel testing, compared with 4.7 weeks for exclusionary testing and 4.8 weeks for sequential testing.
In the CMS population, NGS testing would save about $1.4 million compared with exclusionary testing, more than $1.5 million compared with sequential testing, and about $2.1 million compared with panel testing. In the commercial health plan cohort, NGS would save $3,809 compared with exclusionary testing, $127,402 compared with sequential testing, and $250,842 compared with panel testing.
Dr. Pennell disclosed that he has a consulting or advisory role with AstraZeneca, Lilly, and Regeneron, and that his institution receives research funding from Genentech, NewLink Genetics, Clovis Oncology, Astex Pharmaceuticals, Celgene, AstraZeneca, Pfizer, and Merck. The study received funding from Novartis.
SOURCE: Pennell et al., ASCO Annual Meeting Abstract 9031.
REPORTING FROM THE ASCO ANNUAL MEETING
Key clinical point:
Major finding: Relative to exclusionary, sequential, or panel testing, NGS testing could save up to $2.1 million among CMS beneficiaries and up to $250,842 among patients covered by commercial insurance.
Study details: A decision analytic modeling study in hypothetical cohorts of 1 million insurance plan enrollees.
Disclosures: Dr. Pennell disclosed that he has a consulting or advisory role with AstraZeneca, Lilly, and Regeneron, and that his institution receives research funding from Genentech, NewLink Genetics, Clovis Oncology, Astex Pharmaceuticals, Celgene, AstraZeneca, Pfizer, and Merck. The study received funding from Novartis.
Source: Pennell et al. ASCO Annual Meeting, Abstract 9031.
FDA approves epoetin alfa biosimilar to treat anemia
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
, a treatment for anemia brought on by chronic kidney disease, chemotherapy, or use of zidovudine.
The biosimilar product is also approved to reduce the chance of red blood cell transfusion before and after surgery.
FDA’s approval, issued on May 15, is based on review of structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other safety and effectiveness information showing that the epoetin alfa-epbx is biosimilar to the reference product epoetin alfa. By approving epoetin alfa-epbx as a biosimilar, the FDA is saying that there are “no clinically meaningful differences in safety, purity, and potency” from epoetin alfa.
The agency’s approval comes almost a year after the Oncologic Drugs Advisory Committee voted 14-1 to support approval of the biosimilar. The FDA had rejected the application in 2017, citing manufacturing issues at a facility in Kansas, before ultimately approving the product in 2018.
The biosimilar product must be dispensed with a patient Medication Guide with information about uses and risks and carries a boxed warning about an increased risk of death, heart problems, stroke, and tumor growth or recurrence.
The biosimilar product is marketed by Hospira Inc., a Pfizer company.
Breast cancer: More pathogenic variants detected as multiple-gene sequencing takes over
The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.
Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.
That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.
“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.
Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.
Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.
Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).
Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).
While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.
They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.
They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.
In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.
“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.
Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.
SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.
The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.
Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.
That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.
“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.
Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.
Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.
Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).
Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).
While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.
They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.
They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.
In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.
“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.
Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.
SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.
The introduction of multiple-gene sequencing led to a substantial increase in detection of pathogenic variants in a study of women with breast cancer treated in community practice, results of one retrospective study show.
Multiple-gene sequencing rapidly replaced BRCA1/2 only testing over a 2-year period in the study, driven in part by technological advances and regulatory changes that made comprehensive low-cost genetic testing more accessible, investigators wrote. The report was published in JAMA Oncology.
That quick uptake increased detection of genetic variants that could change care, with no associated increase in prophylactic mastectomy over that same time period, said Allison W. Kurian, MD, of Stanford (Calif.) University, and her coinvestigators.
“The greater yield of clinically relevant information with multiple-gene sequencing offers a major potential advantage over more limited BRCA1/2-only tests,” noted Dr. Kurian and her colleagues.
Their analysis included 5,026 women with stage 0-II breast cancer diagnosed from January 2013 to December 2015 and enrolled in the Individualized Cancer Care (iCan Care) study. That study started enrolling 1 month before a U.S. Supreme Court decision on gene patents, which led to lower costs for multiple-gene sequencing tests for breast cancer risk, Dr. Kurian and her coinvestigators said.
Overall, about one-quarter of women in the study had genetic testing, and that did not change over time. What did change over time was the number of women undergoing multiple-gene testing: In 2013, only 25.6% underwent multiple-gene sequencing, versus 74.4% for BRCA1/2-only testing; by 2015, those figures flipped to 66.5% and 33.5%, respectively.
Multiple-gene sequencing increased detection of pathogenic variants in women at average pretest risk (4.2% versus 2.2% for BRCA1/2-only testing), according to the reported data. Detection was increased in women at high pretest risk due to young age, triple-negative breast cancer, or other factors (12% versus 7.8%).
Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).
While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.
They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.
They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.
In previous experience with BRCA1/2 testing, extensive VUS reclassification occurred after broader testing within the population over 2 decades.
“It is a crucial priority to resolve persistent racial/ethnic disparities in genetic information, particularly as increasingly comprehensive sequencing tests enter clinical practice,” the investigators wrote.
Dr. Kurian reported that Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.
SOURCE: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.
FROM JAMA ONCOLOGY
Key clinical point: For breast cancer patients in community practice, multiple-gene sequencing has rapidly replaced BRCA1/2-only testing, increasing detection of pathogenic variants with no associated increase in prophylactic mastectomy.
Major finding: The rate of pathogenic variant detection was substantially increased with multiple-gene sequencing versus BRCA1/2 only testing for higher-risk patients (12% versus 7.8%) and average risk patients (4.2% versus 2.2%).
Study details: A population-based retrospective cohort study of 5,026 patients with breast cancer diagnosed from January 2013 to December 2015.
Disclosures: Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.
Source: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.
Intravenous antiemetic combination is well tolerated
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
An intravenous combination of fosnetupitant and palonosetron is as well tolerated as is the oral combination for the management of chemotherapy-induced nausea and vomiting, according to a double-blind phase 3 study.
Researchers randomized 404 chemotherapy-naive patients undergoing highly emetogenic chemotherapy for solid tumors to receive a single intravenous dose of 235 mg fosnetupitant and 0.25 mg palonosetron (NEPA) 30 minutes before chemotherapy, or an oral formulation 60 minutes before chemotherapy, with matching placebos.
After a mean of 3.3 doses of intravenous formulation or 3.2 doses of oral formulation, there were similar numbers of treatment-emergent adverse events in the intravenous and oral groups (83.3% vs. 86.6%) but no serious treatment-related adverse events, the investigators wrote. The report was published in Annals of Oncology.
Nearly half of patients in both groups experienced severe adverse events over the course of the study, the most common being neutropenia, anemia, and leukopenia. The most common overall adverse events that occurred during the course of treatment were constipation and increased alanine aminotransferase.
There were very few infusion site treatment-emergent adverse events and none of these were judged to be related to the intravenous infusion of the drug combination.
“Infusion site reactions have been reported for fosaprepitant and IV rolapitant and the product labeling for both includes precaution/warning statements regarding the potential for hypersensitivity reactions/anaphylaxis; in addition, marketed distribution of IV rolapitant was recently suspended as a result of anaphylaxis/anaphylactic shock and hypersensitivity reactions reported in the post-marketing setting,” wrote Lee Schwartzberg, MD, of West Cancer Center, Germantown, Tenn., and his coauthors.
“In light of this, it is noteworthy that there were no injection site reactions considered to be related to IV NEPA over repeated cycles and no instance of anaphylaxis with either formulation of NEPA,” they wrote.
Overall, complete response rates for cycle 1 of treatment were 76.8% in the intravenous group and 84.1% in the oral treatment group, and no emesis rates were also similar (84.2% vs. 88.6%). However, the authors noted that the study was not powered to compare the efficacy of the two formulations.
Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
SOURCE: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.
FROM ANNALS OF ONCOLOGY
Key clinical point: Intravenous fosnetupitant and palonosetron are as well tolerated as is oral formulation.
Major finding: Treatment-emergent adverse events were similar for intravenous and oral fosnetupitant and palonosetron combination.
Study details: Double-blind, randomized phase 3 study of 404 patients undergoing chemotherapy.
Disclosures: Helsinn Healthcare sponsored the study and provided the drugs. Two authors were employees of the company, and four were consultants for the company. Two authors declared research support, advisory roles, and honoraria from pharmaceutical companies including Helsinn Healthcare. Three authors declared no conflicts of interest.
Source: Schwartzberg L et al. Ann Oncol. 2018 May 10. doi: 10.1093/annonc/mdy169/4990798.