AVAHO

A systematic review of immune checkpoint inhibitor (ICI) combinations suggests that they have a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib and should be made generally available to patients with advanced renal cell carcinoma (RCC).

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials that have examined ICIs in combination with VEGF-directed therapies.

In a study published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and one each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared with sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate/poor-risk patients, compared with sunitinib, but the combination led to more frequent discontinuation because of toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation because of toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation because of toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggested that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual-ICI combination therapy was similar to that seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors note that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, IMDC risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

Four of the authors reported receiving honoraria, research funding, or consulting for a variety of pharmaceutical companies, including AbbVie, Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer, Roche, and TerSera.

A systematic review of immune checkpoint inhibitor (ICI) combinations suggests that they have a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib and should be made generally available to patients with advanced renal cell carcinoma (RCC).

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials that have examined ICIs in combination with VEGF-directed therapies.

In a study published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and one each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared with sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate/poor-risk patients, compared with sunitinib, but the combination led to more frequent discontinuation because of toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation because of toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation because of toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggested that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual-ICI combination therapy was similar to that seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors note that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, IMDC risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

Four of the authors reported receiving honoraria, research funding, or consulting for a variety of pharmaceutical companies, including AbbVie, Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer, Roche, and TerSera.

A systematic review of immune checkpoint inhibitor (ICI) combinations suggests that they have a significant survival benefit over the tyrosine kinase inhibitor (TKI) sunitinib and should be made generally available to patients with advanced renal cell carcinoma (RCC).

Until recently, first-line therapy for RCC has primarily been TKIs that target vascular endothelial growth factor (VEGF) and other receptors, including sunitinib and pazopanib. Explorations of novel therapeutic regimens focused on the use of multiple TKIs in combination with monoclonal antibodies that directly inhibit VEGF and inhibitors of the mammalian target of rapamycin (mTOR), such as everolimus.

Some ICIs have already become the preferred first-line treatment for RCC. VEGF and VEGF receptors inhibitors are believed to have immunomodulatory effects, including boosting immune cell infiltration as a result of their effect on tumor vasculature. That idea has spurred recent clinical trials that have examined ICIs in combination with VEGF-directed therapies.

In a study published online in Therapeutic Advances in Medical Oncology, researchers examined six phase 3 clinical trials. Each compared ICI combinations versus sunitinib as first-line therapy for advanced or metastatic RCC. Four of the studies tested TKI/ICI combinations, and one each tested an ICI/anti-VEGF antibody and dual ICIs.

After median follow-ups of 20-30 months, there was no benefit to PD-L1 inhibitor combinations (atezolizumab plus bevacizumab or avelumab plus axitinib) compared with sunitinib. Final survival analyses from one of the trials have not been reported yet.

PD-1 inhibitor combinations fared better. Nivolumab plus ipilimumab led to a 32% reduced risk of death in intermediate/poor-risk patients, compared with sunitinib, but the combination led to more frequent discontinuation because of toxicity (21.8% versus 12.3%). Nivolumab plus cabozantinib produced a 34% reduction in risk of death (P = .003) and a 48% reduction in risk of progression (P < .0001). Rates of discontinuation because of toxicity were similar to sunitinib.

Pembrolizumab combined with TKIs led to a 32% reduced risk of death (P = .003) and a 29% reduced risk of progression (P < .001). Pembrolizumab plus lenvatinib reduced risk of death by 28% (P value not reported) and the risk of progression by 61% (P < .001). Both combinations had a higher frequency of discontinuation because of toxicity (25.9% versus 10.1% and 37.2% versus 14.4%, respectively).

Given that there are no head-to-head comparisons between dual ICI or PD-1/TKI combinations, the researchers suggested that response outcomes may assist in selection between the two approaches. Overall, PD-1/TKI combinations had better overall response rates. The highest was seen in pembrolizumab plus lenvatinib, where frequency of progressive disease ranged from 5.4% to 11.3%. Complete response rate ranged from 8% to 10%.

The authors suggest that upfront treatment with a PD-1 inhibitor and a TKI could be appropriate for patients with a high tumor burden or aggressive disease, in whom stopping tumor growth is urgent and progression could be particularly worrisome.

Safety concerns associated with dual-ICI combination therapy was similar to that seen in RCC and other cancers. Dose delays, rapid diagnostic workups, appropriate timing, and the use of glucocorticoids were among strategies used to manage treatment-related adverse events.

The authors note that five combinations are approved by either the Food and Drug Administration or the European Medicines Agency for first-line treatment of metastatic RCC. Factors to consider for treatment selection include patient and disease characteristics, IMDC risk status, treatment history during earlier disease stage, and eligibility for immunotherapy. Nivolumab plus ipilimumab may be a good choice for patients with an intermediate or poor IMDC risk since it provides a strong and durable overall survival benefit. Pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, and nivolumab plus cabozantinib all have good overall response rates and can prolong life, though extended TKI use can lead to chronic toxicity. Nivolumab plus ipilimumab is not approved for those with a favorable IMDC risk in many regions.

Four of the authors reported receiving honoraria, research funding, or consulting for a variety of pharmaceutical companies, including AbbVie, Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, Novartis, Pfizer, Roche, and TerSera.

A new online tool can quickly and accurately identify individuals who may benefit from genetic testing because they likely carry pathogenic germline variants (PGVs) in a diverse spectrum of cancer susceptibility genes.

The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.

The study was published online  in the Journal of Clinical Oncology.

“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.

Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.

“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
 

Online tool

The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.

A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.

These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.

The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.

In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).

“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.

The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.

Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.

With the second version, the doctor and patient would fill out the information together during an office visit.

PREMMplus would be free for the individual patient or provider.

“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.

“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.

Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

A new online tool can quickly and accurately identify individuals who may benefit from genetic testing because they likely carry pathogenic germline variants (PGVs) in a diverse spectrum of cancer susceptibility genes.

The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.

The study was published online  in the Journal of Clinical Oncology.

“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.

Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.

“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
 

Online tool

The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.

A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.

These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.

The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.

In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).

“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.

The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.

Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.

With the second version, the doctor and patient would fill out the information together during an office visit.

PREMMplus would be free for the individual patient or provider.

“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.

“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.

Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

A new online tool can quickly and accurately identify individuals who may benefit from genetic testing because they likely carry pathogenic germline variants (PGVs) in a diverse spectrum of cancer susceptibility genes.

The PREMMplus online tool was developed and validated by researchers at the Dana-Farber Cancer Institute, Boston using three cohorts involving more than 30,000 individuals who had undergone multigene hereditary cancer risk testing.

The study was published online  in the Journal of Clinical Oncology.

“Our findings show that PREMMplus has the potential to change the model by which patients and family members are referred for genetic testing and counseling,” senior author Sapna Syngal, MD, MPH, with Dana-Farber/Brigham and Women’s Hospital, Boston, said in an institution news release.

Traditionally, when there is concern about a family cancer history, the individual is referred to a genetics clinic, where a counselor takes a complete family history.

“At a time when there’s a shortage of genetic counselors, PREMMplus can help streamline risk assessment and ensure that their time can be focused on where they’re most needed – helping people understand the results of genetic testing and the options available when a cancer-susceptibility gene is found,” Dr. Syngal says.
 

Online tool

The tool uses clinical data (age, sex, ethnicity, and personal/family history of 18 cancers) to determine an individual’s likelihood of harboring a PGV in 19 cancer susceptibility genes.

A PREMMplus score of 2.5% or greater had a 89%-94% sensitivity and > 97% negative predictive value (NPV) for identifying individuals with PGVs in 11 well-defined “category A” high-penetrance cancer risk genes: APC, BRCA1, BRCA2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53.

These PGVs “represent diverse types of inherited cancer risk for which there are established risk-reduction guidelines,” the study team says. Cancers associated with these PGVs include breast, ovarian, colorectal, pancreatic, and prostate cancer, as well as those that make up Lynch syndrome.

The ability of PREMMplus to identify individuals with PGVs in “moderate-penetrance” cancer risk genes (such as CHEK2 and ATM) was somewhat reduced but was still “quite strong” (84%-90% sensitivity and > 93% NPV), the study team reports.

In an interview, Dr. Syngal said her ultimate vision of this online tool is that it will be adapted into the electronic medical record (EMR).

“Through the EMR, it might somehow get pushed out to people before an oncology or primary care appointment or before a mammography or colonoscopy. Then by the time they come in, the doctor or nurse practitioner has the information and can refer them for genetic testing if appropriate,” Dr. Syngal explained.

The tool is not currently available for routine clinical use. The goal is to make it available online in a couple of months.

Dr. Syngal said two versions will be available. One will be a user-friendly version that can be filled out directly by patients and that will tell whether someone passes the threshold of needing genetic testing. The patient would then take that information to their primary care doctor.

With the second version, the doctor and patient would fill out the information together during an office visit.

PREMMplus would be free for the individual patient or provider.

“What we hope is that hospital systems will use it and that insurance companies will also use it as a way to say who needs testing and who to approve for testing,” Dr. Syngal told this news organization.

“For a hospital system or a genetic testing company, for example, that wants to integrate it into their direct-to-consumer platform, they would have to take out a license from Dana-Farber, and cost would be negotiated with each entity based on how they’re going to use it,” Dr. Syngal said.

Funding for the research was provided by the National Institutes of Health. A complete list of author disclosures is available with the original article.

A version of this article first appeared on Medscape.com.

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

A version of this article first appeared on Medscape.com.

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

A version of this article first appeared on Medscape.com.

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

A version of this article first appeared on Medscape.com.

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.

But why? A new analysis finds that the difference can only partly be explained by risky behaviors and carcinogenic exposure.

“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.

“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.

The study was published online in the journal Cancer.

“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.

In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.

“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.

“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
 

Comprehensive analyses

The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.

This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”

However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.

The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.

Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.

“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
 

Details of the analysis 

In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.

However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.

Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.

They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).

The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.

After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).

After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.

The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.

After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.

In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.

The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.

Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.

These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.

There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.

Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”

“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.

“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.

The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.

The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.

No other relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.