Normally, negotiations to use drugs in preclinical studies and clinical trials can take as long as 18 months. But the National Cancer Institute’s (NCI) new drug formulary will allow investigators at NCI-designated cancer centers quicker access to approved and investigational agents, helping make more effective treatments available sooner.

The NCI Formulary, a public-private partnership between NCI and pharmaceutical and biotechnology companies, is one of NCI’s efforts in support of the Cancer Moonshot (ex-Vice President Biden’s call for greater collaboration and faster development of new therapies). The formulary enables NCI to act as an intermediary between investigators at cancer centers and participating pharmaceutical companies, streamlining arrangements for access to and use of drugs.

The formulary launched with 15 targeted agents from 6 pharmaceutical companies: Bristol-Myers Squibb, Eli Lilly and Company, Genentech, Kyowa Hakko Kirin, Loxo Oncology, and Xcovery Holding Company LLC.

Normally, negotiations to use drugs in preclinical studies and clinical trials can take as long as 18 months. But the National Cancer Institute’s (NCI) new drug formulary will allow investigators at NCI-designated cancer centers quicker access to approved and investigational agents, helping make more effective treatments available sooner.

The NCI Formulary, a public-private partnership between NCI and pharmaceutical and biotechnology companies, is one of NCI’s efforts in support of the Cancer Moonshot (ex-Vice President Biden’s call for greater collaboration and faster development of new therapies). The formulary enables NCI to act as an intermediary between investigators at cancer centers and participating pharmaceutical companies, streamlining arrangements for access to and use of drugs.

The formulary launched with 15 targeted agents from 6 pharmaceutical companies: Bristol-Myers Squibb, Eli Lilly and Company, Genentech, Kyowa Hakko Kirin, Loxo Oncology, and Xcovery Holding Company LLC.

Normally, negotiations to use drugs in preclinical studies and clinical trials can take as long as 18 months. But the National Cancer Institute’s (NCI) new drug formulary will allow investigators at NCI-designated cancer centers quicker access to approved and investigational agents, helping make more effective treatments available sooner.

The NCI Formulary, a public-private partnership between NCI and pharmaceutical and biotechnology companies, is one of NCI’s efforts in support of the Cancer Moonshot (ex-Vice President Biden’s call for greater collaboration and faster development of new therapies). The formulary enables NCI to act as an intermediary between investigators at cancer centers and participating pharmaceutical companies, streamlining arrangements for access to and use of drugs.

The formulary launched with 15 targeted agents from 6 pharmaceutical companies: Bristol-Myers Squibb, Eli Lilly and Company, Genentech, Kyowa Hakko Kirin, Loxo Oncology, and Xcovery Holding Company LLC.

Ginsenosides are pharmacologically active components of ginseng, which often is used to relieve coughs and colds. They also have been found to have antineoplastic, antioxidant, antimicrobial, and antifungal properties; other studies suggest neuroprotective properties as well. Ginsenosides may act against coxsackievirus B3, enterovirus 71, human rhinovirus 3, and hemagglutinating virus of Japan (HVJ) infection. But do they have an antiviral effect on influenza?

Related: A New Kind of Flu Drug

Researchers from University Health Network & Shantou University Medical College and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, both in China, and University of Toronto in Canada conducted a study in mice of the anti-influenza properties of ginseng and ginseng-derived compounds both in vitro and in vivo. They found that ginsenosides exerted “strong antiviral activity” to 2009 pandemic H1N1 virus. Ginsenoside protected the animals from infection and lowered viral titers in their lungs.

Sugars were the key to the effectiveness of the ginsenosides, which are composed of a steroid skeleton with various sugar groups attached. The researchers note that previous studies have shown that ginsenosides’ anticancer activity and antioxidant activity are related to the type and position of sugar moieties.

Related: How Common is Flu Without Fever?

The pilot experiment did not have negative or toxic effects on the animals or in cell proliferation in vitro, thus “defining the nontoxic nature and therapeutic value of these compounds,” the researchers say. They also point out that in phase 2 randomized clinical trials in children, oral consumption of ginseng extract as an alternative influenza treatment did not result in severe adverse effects. They suggest that their findings could spur other research into a novel antiviral drug for influenza.

Source:

Dong W, Farooqui A, Leon AJ, Kelvin DJ. PloS One. 2017;12(2):e0171936.
doi: 10.1371/journal.pone.0171936.

Ginsenosides are pharmacologically active components of ginseng, which often is used to relieve coughs and colds. They also have been found to have antineoplastic, antioxidant, antimicrobial, and antifungal properties; other studies suggest neuroprotective properties as well. Ginsenosides may act against coxsackievirus B3, enterovirus 71, human rhinovirus 3, and hemagglutinating virus of Japan (HVJ) infection. But do they have an antiviral effect on influenza?

Related: A New Kind of Flu Drug

Researchers from University Health Network & Shantou University Medical College and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, both in China, and University of Toronto in Canada conducted a study in mice of the anti-influenza properties of ginseng and ginseng-derived compounds both in vitro and in vivo. They found that ginsenosides exerted “strong antiviral activity” to 2009 pandemic H1N1 virus. Ginsenoside protected the animals from infection and lowered viral titers in their lungs.

Sugars were the key to the effectiveness of the ginsenosides, which are composed of a steroid skeleton with various sugar groups attached. The researchers note that previous studies have shown that ginsenosides’ anticancer activity and antioxidant activity are related to the type and position of sugar moieties.

Related: How Common is Flu Without Fever?

The pilot experiment did not have negative or toxic effects on the animals or in cell proliferation in vitro, thus “defining the nontoxic nature and therapeutic value of these compounds,” the researchers say. They also point out that in phase 2 randomized clinical trials in children, oral consumption of ginseng extract as an alternative influenza treatment did not result in severe adverse effects. They suggest that their findings could spur other research into a novel antiviral drug for influenza.

Source:

Dong W, Farooqui A, Leon AJ, Kelvin DJ. PloS One. 2017;12(2):e0171936.
doi: 10.1371/journal.pone.0171936.

Ginsenosides are pharmacologically active components of ginseng, which often is used to relieve coughs and colds. They also have been found to have antineoplastic, antioxidant, antimicrobial, and antifungal properties; other studies suggest neuroprotective properties as well. Ginsenosides may act against coxsackievirus B3, enterovirus 71, human rhinovirus 3, and hemagglutinating virus of Japan (HVJ) infection. But do they have an antiviral effect on influenza?

Related: A New Kind of Flu Drug

Researchers from University Health Network & Shantou University Medical College and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, both in China, and University of Toronto in Canada conducted a study in mice of the anti-influenza properties of ginseng and ginseng-derived compounds both in vitro and in vivo. They found that ginsenosides exerted “strong antiviral activity” to 2009 pandemic H1N1 virus. Ginsenoside protected the animals from infection and lowered viral titers in their lungs.

Sugars were the key to the effectiveness of the ginsenosides, which are composed of a steroid skeleton with various sugar groups attached. The researchers note that previous studies have shown that ginsenosides’ anticancer activity and antioxidant activity are related to the type and position of sugar moieties.

Related: How Common is Flu Without Fever?

The pilot experiment did not have negative or toxic effects on the animals or in cell proliferation in vitro, thus “defining the nontoxic nature and therapeutic value of these compounds,” the researchers say. They also point out that in phase 2 randomized clinical trials in children, oral consumption of ginseng extract as an alternative influenza treatment did not result in severe adverse effects. They suggest that their findings could spur other research into a novel antiviral drug for influenza.

Source:

Dong W, Farooqui A, Leon AJ, Kelvin DJ. PloS One. 2017;12(2):e0171936.
doi: 10.1371/journal.pone.0171936.

A 58-year-old woman with T2DM and heart failure returns to your office for follow-up. She has been on the maximum dose of metformin alone for the past six months, but her A1C is now 7.8%. She wants to avoid injections. What do you recommend?

There is surprisingly little consensus about what to add to metformin for patients with T2DM who require a second agent to achieve their glycemic goal. Attaining glycemic control earlier in the course of the disease may lead to reduced overall cardiovascular (CV) risk, so the choice of a second drug is an important one.² While the proven mortality benefit, wide availability, and low cost of metformin make it well-established as initial pharmacotherapy, no second-choice drug has amassed enough evidence of benefit to become the add-on therapy of choice.

The professional societies are of little assistance; dual-therapy recommendations from the American Diabetes Association and the European Association for the Study of Diabetes do not specify a preference.³ Although the American Association of Clinical Endocrinologists/American College of Endocrinology suggest a hierarchy of choices, it is based on expert consensus recommendations.⁴

A look at the options

Options for add-on therapy include sulfonylureas, thiazolidines, DPP-4 inhibitors, sodium glucose cotransporter 2 inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and insulin. Providers frequently prescribe sulfonylureas after metformin because they are low in cost, have long-term safety data, and are effective at lowering A1C. They work by directly stimulating insulin secretion via pancreatic ß-cells in a glucose-independent manner. But as a 2010 meta-analysis revealed, sulfonylureas carry significant risk for hypoglycemia (relative risk [RR], 4.57) and weight gain (average, 2.06 kg), compared to placebo.⁵

DPP-4 inhibitors, on the other hand, induce insulin secretion in a glucose-dependent manner through an incretin mechanism. Combined with metformin, they provide glucose control similar to that achieved with the combination of a sulfonylurea and metformin.⁶ DPP-4 inhibitors were initially found to be associated with fewer CV events and less hypoglycemia than sulfonylureas but were subsequently linked to an increased risk for heart failure–related hospitalization.⁷

A recent study provides more data on the effects of DPP-4s added to metformin.¹

STUDY SUMMARY

DPP-4s as effective, less risky

This observational cohort study compared DPP-4 inhibitors and sulfonylureas when combined with metformin for the treatment of T2DM.¹ Outcomes were all-cause mortality, major adverse CV events (defined as hospitalization for ischemic stroke or myocardial infarction [MI]), and hospitalizations for either heart failure or hypoglycemia. The study included data from the National Health Insurance Research Database in Taiwan on more than 70,000 patients (ages 20 and older) with diagnosed T2DM. Individuals adherent to metformin were considered to be enrolled in the cohort on the day they began using either a DPP-4 inhibitor or a sulfonylurea, in addition to metformin.

The researchers collected additional data on socioeconomic factors, urbanization, robustness of the local health care system, Charlson Comorbidity Index, adapted Diabetes Complications Severity Index, and other comorbidities and medications that could affect the outcomes of interest. Participants were then matched by propensity score into 10,089 pairs, each consisting of one DPP-4 inhibitor user and one sulfonylurea user.

After mean follow-up of 2.8 years, the investigators used Cox regression analysis to evaluate the relative hazards of the outcomes. Subgroup analysis stratified by age, sex, Charlson Comorbidity Index, hypertension, chronic kidney disease, hospitalization for heart failure, MI, and cerebrovascular disease yielded results similar to those of the primary analysis for each outcome. Similar results were also obtained when the data were analyzed without propensity-score matching.

The researchers found that users of DPP-4 inhibitors—compared with those who used sulfonylureas—had a lower risk for all-cause mortality (366 vs 488 deaths; hazard ratio [HR], 0.63; number needed to treat [NNT], 117), major cardiac events (209 vs 282 events; HR, 0.68; NNT, 191), ischemic stroke (144 vs 203 strokes; HR, 0.64; NNT, 246), and hypoglycemia (89 vs 170 events; HR, 0.43; NNT, 201). There were no significant differences in the occurrence of MIs (69 vs 88 MIs; HR, 0.75) or the number of hospitalizations for heart failure (100 vs 100 events; HR, 0.78) between the two groups.

WHAT’S NEW

Lower risks for death, CV events, and hypoglycemia

This study found that when added to metformin, DPP-4 inhibitors were associated with lower risks for all-cause mortality, CV events, and hypoglycemia when compared to sulfonylureas. Additionally, DPP-4 inhibitors did not increase the risk for heart failure hospitalization. A recent multicenter observational study of nearly 1.5 million patients on the effects of incretin-based treatments (including DPP-4 inhibitors and GLP-1 agonists) found no increased risk for heart failure hospitalization with DPP-4 inhibitors, compared to other combinations of oral T2DM agents.⁸

CAVEATS

Did unmeasured confounders play a role?

Unmeasured confounders potentially bias all observational population cohort results. In this particular study, there may have been unmeasured but significant patient factors that providers used to choose diabetes medications. Also, the study did not evaluate diabetes control, although previous studies have shown similar glucose control between sulfonylureas and DPP-4 inhibitors when added to metformin.⁶

Another caveat is that the results from this study group may not be generalizable to other populations due to physiologic differences. People of Asian ancestry are at risk for T2DM at a lower BMI than people of European ancestry, which could affect the outcomes of interest.⁹

Furthermore, the study did not evaluate outcomes based on whether patients were taking first-, second-, or third-generation sulfonylureas. Some sulfonylureas (eg, glyburide) carry a higher risk for hypoglycemia, which could bias the results.¹⁰

Lastly, the study only provides guidance when choosing between a sulfonylurea and a DPP-4 inhibitor for secondline pharmacotherapy. The GRADE trial, due to be completed in 2023, is comparing sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and insulin as add-on medications to metformin; it may provide more data on which to base treatment decisions.¹¹

CHALLENGES TO IMPLEMENTATION

DPP-4s are more expensive

Sulfonylureas and DPP-4 inhibitors are both available as generic medications, but the cost of DPP-4 inhibitors remains significantly higher.¹² Higher copays and deductibles could affect patient preference. For patients without health insurance, sulfonylureas are available on the discounted drug lists of many major retailers, while DPP-4 inhibitors are not.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(1):42-44.

A 58-year-old woman with T2DM and heart failure returns to your office for follow-up. She has been on the maximum dose of metformin alone for the past six months, but her A1C is now 7.8%. She wants to avoid injections. What do you recommend?

There is surprisingly little consensus about what to add to metformin for patients with T2DM who require a second agent to achieve their glycemic goal. Attaining glycemic control earlier in the course of the disease may lead to reduced overall cardiovascular (CV) risk, so the choice of a second drug is an important one.² While the proven mortality benefit, wide availability, and low cost of metformin make it well-established as initial pharmacotherapy, no second-choice drug has amassed enough evidence of benefit to become the add-on therapy of choice.

The professional societies are of little assistance; dual-therapy recommendations from the American Diabetes Association and the European Association for the Study of Diabetes do not specify a preference.³ Although the American Association of Clinical Endocrinologists/American College of Endocrinology suggest a hierarchy of choices, it is based on expert consensus recommendations.⁴

A look at the options

Options for add-on therapy include sulfonylureas, thiazolidines, DPP-4 inhibitors, sodium glucose cotransporter 2 inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and insulin. Providers frequently prescribe sulfonylureas after metformin because they are low in cost, have long-term safety data, and are effective at lowering A1C. They work by directly stimulating insulin secretion via pancreatic ß-cells in a glucose-independent manner. But as a 2010 meta-analysis revealed, sulfonylureas carry significant risk for hypoglycemia (relative risk [RR], 4.57) and weight gain (average, 2.06 kg), compared to placebo.⁵

DPP-4 inhibitors, on the other hand, induce insulin secretion in a glucose-dependent manner through an incretin mechanism. Combined with metformin, they provide glucose control similar to that achieved with the combination of a sulfonylurea and metformin.⁶ DPP-4 inhibitors were initially found to be associated with fewer CV events and less hypoglycemia than sulfonylureas but were subsequently linked to an increased risk for heart failure–related hospitalization.⁷

A recent study provides more data on the effects of DPP-4s added to metformin.¹

STUDY SUMMARY

DPP-4s as effective, less risky

This observational cohort study compared DPP-4 inhibitors and sulfonylureas when combined with metformin for the treatment of T2DM.¹ Outcomes were all-cause mortality, major adverse CV events (defined as hospitalization for ischemic stroke or myocardial infarction [MI]), and hospitalizations for either heart failure or hypoglycemia. The study included data from the National Health Insurance Research Database in Taiwan on more than 70,000 patients (ages 20 and older) with diagnosed T2DM. Individuals adherent to metformin were considered to be enrolled in the cohort on the day they began using either a DPP-4 inhibitor or a sulfonylurea, in addition to metformin.

The researchers collected additional data on socioeconomic factors, urbanization, robustness of the local health care system, Charlson Comorbidity Index, adapted Diabetes Complications Severity Index, and other comorbidities and medications that could affect the outcomes of interest. Participants were then matched by propensity score into 10,089 pairs, each consisting of one DPP-4 inhibitor user and one sulfonylurea user.

After mean follow-up of 2.8 years, the investigators used Cox regression analysis to evaluate the relative hazards of the outcomes. Subgroup analysis stratified by age, sex, Charlson Comorbidity Index, hypertension, chronic kidney disease, hospitalization for heart failure, MI, and cerebrovascular disease yielded results similar to those of the primary analysis for each outcome. Similar results were also obtained when the data were analyzed without propensity-score matching.

The researchers found that users of DPP-4 inhibitors—compared with those who used sulfonylureas—had a lower risk for all-cause mortality (366 vs 488 deaths; hazard ratio [HR], 0.63; number needed to treat [NNT], 117), major cardiac events (209 vs 282 events; HR, 0.68; NNT, 191), ischemic stroke (144 vs 203 strokes; HR, 0.64; NNT, 246), and hypoglycemia (89 vs 170 events; HR, 0.43; NNT, 201). There were no significant differences in the occurrence of MIs (69 vs 88 MIs; HR, 0.75) or the number of hospitalizations for heart failure (100 vs 100 events; HR, 0.78) between the two groups.

WHAT’S NEW

Lower risks for death, CV events, and hypoglycemia

This study found that when added to metformin, DPP-4 inhibitors were associated with lower risks for all-cause mortality, CV events, and hypoglycemia when compared to sulfonylureas. Additionally, DPP-4 inhibitors did not increase the risk for heart failure hospitalization. A recent multicenter observational study of nearly 1.5 million patients on the effects of incretin-based treatments (including DPP-4 inhibitors and GLP-1 agonists) found no increased risk for heart failure hospitalization with DPP-4 inhibitors, compared to other combinations of oral T2DM agents.⁸

CAVEATS

Did unmeasured confounders play a role?

Unmeasured confounders potentially bias all observational population cohort results. In this particular study, there may have been unmeasured but significant patient factors that providers used to choose diabetes medications. Also, the study did not evaluate diabetes control, although previous studies have shown similar glucose control between sulfonylureas and DPP-4 inhibitors when added to metformin.⁶

Another caveat is that the results from this study group may not be generalizable to other populations due to physiologic differences. People of Asian ancestry are at risk for T2DM at a lower BMI than people of European ancestry, which could affect the outcomes of interest.⁹

Furthermore, the study did not evaluate outcomes based on whether patients were taking first-, second-, or third-generation sulfonylureas. Some sulfonylureas (eg, glyburide) carry a higher risk for hypoglycemia, which could bias the results.¹⁰

Lastly, the study only provides guidance when choosing between a sulfonylurea and a DPP-4 inhibitor for secondline pharmacotherapy. The GRADE trial, due to be completed in 2023, is comparing sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and insulin as add-on medications to metformin; it may provide more data on which to base treatment decisions.¹¹

CHALLENGES TO IMPLEMENTATION

DPP-4s are more expensive

Sulfonylureas and DPP-4 inhibitors are both available as generic medications, but the cost of DPP-4 inhibitors remains significantly higher.¹² Higher copays and deductibles could affect patient preference. For patients without health insurance, sulfonylureas are available on the discounted drug lists of many major retailers, while DPP-4 inhibitors are not.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(1):42-44.

A 58-year-old woman with T2DM and heart failure returns to your office for follow-up. She has been on the maximum dose of metformin alone for the past six months, but her A1C is now 7.8%. She wants to avoid injections. What do you recommend?

There is surprisingly little consensus about what to add to metformin for patients with T2DM who require a second agent to achieve their glycemic goal. Attaining glycemic control earlier in the course of the disease may lead to reduced overall cardiovascular (CV) risk, so the choice of a second drug is an important one.² While the proven mortality benefit, wide availability, and low cost of metformin make it well-established as initial pharmacotherapy, no second-choice drug has amassed enough evidence of benefit to become the add-on therapy of choice.

The professional societies are of little assistance; dual-therapy recommendations from the American Diabetes Association and the European Association for the Study of Diabetes do not specify a preference.³ Although the American Association of Clinical Endocrinologists/American College of Endocrinology suggest a hierarchy of choices, it is based on expert consensus recommendations.⁴

A look at the options

Options for add-on therapy include sulfonylureas, thiazolidines, DPP-4 inhibitors, sodium glucose cotransporter 2 inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and insulin. Providers frequently prescribe sulfonylureas after metformin because they are low in cost, have long-term safety data, and are effective at lowering A1C. They work by directly stimulating insulin secretion via pancreatic ß-cells in a glucose-independent manner. But as a 2010 meta-analysis revealed, sulfonylureas carry significant risk for hypoglycemia (relative risk [RR], 4.57) and weight gain (average, 2.06 kg), compared to placebo.⁵

DPP-4 inhibitors, on the other hand, induce insulin secretion in a glucose-dependent manner through an incretin mechanism. Combined with metformin, they provide glucose control similar to that achieved with the combination of a sulfonylurea and metformin.⁶ DPP-4 inhibitors were initially found to be associated with fewer CV events and less hypoglycemia than sulfonylureas but were subsequently linked to an increased risk for heart failure–related hospitalization.⁷

A recent study provides more data on the effects of DPP-4s added to metformin.¹

STUDY SUMMARY

DPP-4s as effective, less risky

This observational cohort study compared DPP-4 inhibitors and sulfonylureas when combined with metformin for the treatment of T2DM.¹ Outcomes were all-cause mortality, major adverse CV events (defined as hospitalization for ischemic stroke or myocardial infarction [MI]), and hospitalizations for either heart failure or hypoglycemia. The study included data from the National Health Insurance Research Database in Taiwan on more than 70,000 patients (ages 20 and older) with diagnosed T2DM. Individuals adherent to metformin were considered to be enrolled in the cohort on the day they began using either a DPP-4 inhibitor or a sulfonylurea, in addition to metformin.

The researchers collected additional data on socioeconomic factors, urbanization, robustness of the local health care system, Charlson Comorbidity Index, adapted Diabetes Complications Severity Index, and other comorbidities and medications that could affect the outcomes of interest. Participants were then matched by propensity score into 10,089 pairs, each consisting of one DPP-4 inhibitor user and one sulfonylurea user.

After mean follow-up of 2.8 years, the investigators used Cox regression analysis to evaluate the relative hazards of the outcomes. Subgroup analysis stratified by age, sex, Charlson Comorbidity Index, hypertension, chronic kidney disease, hospitalization for heart failure, MI, and cerebrovascular disease yielded results similar to those of the primary analysis for each outcome. Similar results were also obtained when the data were analyzed without propensity-score matching.

The researchers found that users of DPP-4 inhibitors—compared with those who used sulfonylureas—had a lower risk for all-cause mortality (366 vs 488 deaths; hazard ratio [HR], 0.63; number needed to treat [NNT], 117), major cardiac events (209 vs 282 events; HR, 0.68; NNT, 191), ischemic stroke (144 vs 203 strokes; HR, 0.64; NNT, 246), and hypoglycemia (89 vs 170 events; HR, 0.43; NNT, 201). There were no significant differences in the occurrence of MIs (69 vs 88 MIs; HR, 0.75) or the number of hospitalizations for heart failure (100 vs 100 events; HR, 0.78) between the two groups.

WHAT’S NEW

Lower risks for death, CV events, and hypoglycemia

This study found that when added to metformin, DPP-4 inhibitors were associated with lower risks for all-cause mortality, CV events, and hypoglycemia when compared to sulfonylureas. Additionally, DPP-4 inhibitors did not increase the risk for heart failure hospitalization. A recent multicenter observational study of nearly 1.5 million patients on the effects of incretin-based treatments (including DPP-4 inhibitors and GLP-1 agonists) found no increased risk for heart failure hospitalization with DPP-4 inhibitors, compared to other combinations of oral T2DM agents.⁸

CAVEATS

Did unmeasured confounders play a role?

Unmeasured confounders potentially bias all observational population cohort results. In this particular study, there may have been unmeasured but significant patient factors that providers used to choose diabetes medications. Also, the study did not evaluate diabetes control, although previous studies have shown similar glucose control between sulfonylureas and DPP-4 inhibitors when added to metformin.⁶

Another caveat is that the results from this study group may not be generalizable to other populations due to physiologic differences. People of Asian ancestry are at risk for T2DM at a lower BMI than people of European ancestry, which could affect the outcomes of interest.⁹

Furthermore, the study did not evaluate outcomes based on whether patients were taking first-, second-, or third-generation sulfonylureas. Some sulfonylureas (eg, glyburide) carry a higher risk for hypoglycemia, which could bias the results.¹⁰

Lastly, the study only provides guidance when choosing between a sulfonylurea and a DPP-4 inhibitor for secondline pharmacotherapy. The GRADE trial, due to be completed in 2023, is comparing sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and insulin as add-on medications to metformin; it may provide more data on which to base treatment decisions.¹¹

CHALLENGES TO IMPLEMENTATION

DPP-4s are more expensive

Sulfonylureas and DPP-4 inhibitors are both available as generic medications, but the cost of DPP-4 inhibitors remains significantly higher.¹² Higher copays and deductibles could affect patient preference. For patients without health insurance, sulfonylureas are available on the discounted drug lists of many major retailers, while DPP-4 inhibitors are not.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(1):42-44.

Clinical question: Is there an association between time to completion of discharge summary and hospital readmission?

Background: Thirty-day hospital readmission is one of the quality indicators for inpatient care and a higher rate can result in monetary penalties. Several interventions aimed at reducing this occurrence have been studied in different settings with variable success. Timely completion of discharge summary can possibly affect readmissions by providing crucial information to outpatient providers caring for patients across the care continuum.

Study design: Retrospective cohort study.

Setting: Johns Hopkins University, Baltimore.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Clinical question: Is there an association between time to completion of discharge summary and hospital readmission?

Background: Thirty-day hospital readmission is one of the quality indicators for inpatient care and a higher rate can result in monetary penalties. Several interventions aimed at reducing this occurrence have been studied in different settings with variable success. Timely completion of discharge summary can possibly affect readmissions by providing crucial information to outpatient providers caring for patients across the care continuum.

Study design: Retrospective cohort study.

Setting: Johns Hopkins University, Baltimore.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Clinical question: Is there an association between time to completion of discharge summary and hospital readmission?

Background: Thirty-day hospital readmission is one of the quality indicators for inpatient care and a higher rate can result in monetary penalties. Several interventions aimed at reducing this occurrence have been studied in different settings with variable success. Timely completion of discharge summary can possibly affect readmissions by providing crucial information to outpatient providers caring for patients across the care continuum.

Study design: Retrospective cohort study.

Setting: Johns Hopkins University, Baltimore.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Clinical question: What are the epidemiology, risk factors, and associated morbidity and mortality of acute kidney injury (AKI) in critically ill children and young adults?

Background: Adult studies on acute kidney injury have shown increasing mortality and morbidity when both plasma creatinine and urine output were used to diagnose AKI than when used alone. Studies of AKI in children have also been limited.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Clinical question: What are the epidemiology, risk factors, and associated morbidity and mortality of acute kidney injury (AKI) in critically ill children and young adults?

Background: Adult studies on acute kidney injury have shown increasing mortality and morbidity when both plasma creatinine and urine output were used to diagnose AKI than when used alone. Studies of AKI in children have also been limited.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Clinical question: What are the epidemiology, risk factors, and associated morbidity and mortality of acute kidney injury (AKI) in critically ill children and young adults?

Background: Adult studies on acute kidney injury have shown increasing mortality and morbidity when both plasma creatinine and urine output were used to diagnose AKI than when used alone. Studies of AKI in children have also been limited.

Dr. Rachoin is an assistant professor of clinical medicine and associate division head, Hospital Medicine, at Cooper Medical School at Rowan University. He works as a hospitalist at Cooper University Hospital in Camden, N.J.

Acquired BTK^C481S and PLCG2 mutations led to ibrutinib resistance in chronic lymphocytic leukemia (CLL), investigators reported online in the Journal of Clinical Oncology.

These mutations preceded 85% of clinical relapses, appearing a median of 9.3 months beforehand, Jennifer A. Woyach, MD, and her associates from the Ohio State University, Columbus, concluded from a retrospective study of 308 patients. In a separate prospective study of 112 patients, acquired BTK^C481S mutation and clonal expansion preceded all eight cases of relapse, they said. “Relapse of CLL after ibrutinib is an issue of increasing clinical significance,” they concluded. “We show that mutations in Bruton tyrosine kinase (BTK) and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.”

Ibrutinib has transformed the CLL treatment landscape, but patients face poor outcomes if they relapse with Richter transformation or develop progressive disease. Past work has linked ibrutinib resistance to acquired mutations in BTK at the binding site of ibrutinib and in PLCG2 located just downstream. But the scope of ibrutinib resistance in CLL and key mutational players were unknown (J Clin Oncol. 2017. doi: 10.1200/JCO.2016.70.2282).

To fill that gap, the researchers retrospectively analyzed data from four sequential ibrutinib CLL trials at the Ohio State University. The separate prospective analysis involved analyzing the entire BTK and PLCG2 coding regions every 3 months.

In the retrospective study, patients had received a median of 3 and up to 16 prior therapies. Given the median follow-up period of 3.4 years, about 19% of patients experienced clinical relapse within 4 years of starting ibrutinib, the researchers estimated (95% confidence interval, 14%-24%). Deep sequencing by Ion Torrent (Life Technologies) identified mutations in BTK^C481S and/or PLCG2, in 40 of 47 (85%) relapses. In 31 cases, BTK^C481S was the sole mutation. Mutational burdens varied among patients, but generally correlated with CLL progression in peripheral blood versus primarily nodal relapse.

At baseline, 172 (58%) of retrospective study participants had complex cytogenetics, 52% had del(13q), 40% had del(17p), and 21% had MYC abnormality. Median age was 65 years (range, 26-91 years) and 70% of patients were female. Multivariable analyses linked transformation to complex karyotype (hazard ratio, 5.0; 95% CI, 1.5-16.5) and MYC abnormality (HR, 2.5; 95% CI, 1.0-4.7), and linked progressive CLL to age younger than 65 years, complex karyotype, and del(17)(p13.1).

Richter transformation usually occurred within 2 years of starting ibrutinib and had a cumulative 4-year incidence of 10%, the investigators also reported. Patients survived a median of only 3.9 months after stopping ibrutinib because of transformation. The cumulative rate of progressive CLL was higher (19.1%), but early progression was rare, and patients who stopped ibrutinib because of progression survived longer (median, 22.7 months).

In the prospective study, all eight patients with BTK^C481S who had not yet clinically relapsed nonetheless had increasing frequency of this mutation over time, the investigators reported. Together, the findings confirm BTK and PLCG2 mutations as the key players in CLL resistance to ibrutinib, they stated. Perhaps most importantly, they reveal “a prolonged period of asymptomatic clonal expression” in CLL that precedes clinical relapse and provides a window of opportunity to target these cells with novel therapies in clinical trials, they wrote.

Given that ibrutinib was approved for use in relapsed CLL only 2 years ago, “We are likely just starting to see the first emergence of relapse in the community setting,” the researchers concluded. “Enhanced knowledge of both the molecular and clinical mechanisms of relapse may allow for strategic alterations in monitoring and management that could change the natural history of ibrutinib resistance.”

Funding sources included the D. Warren Brown Foundation, Mr. and Mrs. Michael Thomas, the Four Winds Foundation, the Leukemia and Lymphoma Society, Pelotonia, and the National Cancer Institute. Pharmacyclics also provided partial support. Dr. Woyach disclosed ties to Janssen, Acerta Pharma, Karyopharm Therapeutics, and MorphoSys, and a provisional patent related to ^C481S detection.

Acquired BTK^C481S and PLCG2 mutations led to ibrutinib resistance in chronic lymphocytic leukemia (CLL), investigators reported online in the Journal of Clinical Oncology.

These mutations preceded 85% of clinical relapses, appearing a median of 9.3 months beforehand, Jennifer A. Woyach, MD, and her associates from the Ohio State University, Columbus, concluded from a retrospective study of 308 patients. In a separate prospective study of 112 patients, acquired BTK^C481S mutation and clonal expansion preceded all eight cases of relapse, they said. “Relapse of CLL after ibrutinib is an issue of increasing clinical significance,” they concluded. “We show that mutations in Bruton tyrosine kinase (BTK) and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.”

Ibrutinib has transformed the CLL treatment landscape, but patients face poor outcomes if they relapse with Richter transformation or develop progressive disease. Past work has linked ibrutinib resistance to acquired mutations in BTK at the binding site of ibrutinib and in PLCG2 located just downstream. But the scope of ibrutinib resistance in CLL and key mutational players were unknown (J Clin Oncol. 2017. doi: 10.1200/JCO.2016.70.2282).

To fill that gap, the researchers retrospectively analyzed data from four sequential ibrutinib CLL trials at the Ohio State University. The separate prospective analysis involved analyzing the entire BTK and PLCG2 coding regions every 3 months.

In the retrospective study, patients had received a median of 3 and up to 16 prior therapies. Given the median follow-up period of 3.4 years, about 19% of patients experienced clinical relapse within 4 years of starting ibrutinib, the researchers estimated (95% confidence interval, 14%-24%). Deep sequencing by Ion Torrent (Life Technologies) identified mutations in BTK^C481S and/or PLCG2, in 40 of 47 (85%) relapses. In 31 cases, BTK^C481S was the sole mutation. Mutational burdens varied among patients, but generally correlated with CLL progression in peripheral blood versus primarily nodal relapse.

At baseline, 172 (58%) of retrospective study participants had complex cytogenetics, 52% had del(13q), 40% had del(17p), and 21% had MYC abnormality. Median age was 65 years (range, 26-91 years) and 70% of patients were female. Multivariable analyses linked transformation to complex karyotype (hazard ratio, 5.0; 95% CI, 1.5-16.5) and MYC abnormality (HR, 2.5; 95% CI, 1.0-4.7), and linked progressive CLL to age younger than 65 years, complex karyotype, and del(17)(p13.1).

Richter transformation usually occurred within 2 years of starting ibrutinib and had a cumulative 4-year incidence of 10%, the investigators also reported. Patients survived a median of only 3.9 months after stopping ibrutinib because of transformation. The cumulative rate of progressive CLL was higher (19.1%), but early progression was rare, and patients who stopped ibrutinib because of progression survived longer (median, 22.7 months).

In the prospective study, all eight patients with BTK^C481S who had not yet clinically relapsed nonetheless had increasing frequency of this mutation over time, the investigators reported. Together, the findings confirm BTK and PLCG2 mutations as the key players in CLL resistance to ibrutinib, they stated. Perhaps most importantly, they reveal “a prolonged period of asymptomatic clonal expression” in CLL that precedes clinical relapse and provides a window of opportunity to target these cells with novel therapies in clinical trials, they wrote.

Given that ibrutinib was approved for use in relapsed CLL only 2 years ago, “We are likely just starting to see the first emergence of relapse in the community setting,” the researchers concluded. “Enhanced knowledge of both the molecular and clinical mechanisms of relapse may allow for strategic alterations in monitoring and management that could change the natural history of ibrutinib resistance.”

Funding sources included the D. Warren Brown Foundation, Mr. and Mrs. Michael Thomas, the Four Winds Foundation, the Leukemia and Lymphoma Society, Pelotonia, and the National Cancer Institute. Pharmacyclics also provided partial support. Dr. Woyach disclosed ties to Janssen, Acerta Pharma, Karyopharm Therapeutics, and MorphoSys, and a provisional patent related to ^C481S detection.

Acquired BTK^C481S and PLCG2 mutations led to ibrutinib resistance in chronic lymphocytic leukemia (CLL), investigators reported online in the Journal of Clinical Oncology.

These mutations preceded 85% of clinical relapses, appearing a median of 9.3 months beforehand, Jennifer A. Woyach, MD, and her associates from the Ohio State University, Columbus, concluded from a retrospective study of 308 patients. In a separate prospective study of 112 patients, acquired BTK^C481S mutation and clonal expansion preceded all eight cases of relapse, they said. “Relapse of CLL after ibrutinib is an issue of increasing clinical significance,” they concluded. “We show that mutations in Bruton tyrosine kinase (BTK) and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.”

Ibrutinib has transformed the CLL treatment landscape, but patients face poor outcomes if they relapse with Richter transformation or develop progressive disease. Past work has linked ibrutinib resistance to acquired mutations in BTK at the binding site of ibrutinib and in PLCG2 located just downstream. But the scope of ibrutinib resistance in CLL and key mutational players were unknown (J Clin Oncol. 2017. doi: 10.1200/JCO.2016.70.2282).

To fill that gap, the researchers retrospectively analyzed data from four sequential ibrutinib CLL trials at the Ohio State University. The separate prospective analysis involved analyzing the entire BTK and PLCG2 coding regions every 3 months.

In the retrospective study, patients had received a median of 3 and up to 16 prior therapies. Given the median follow-up period of 3.4 years, about 19% of patients experienced clinical relapse within 4 years of starting ibrutinib, the researchers estimated (95% confidence interval, 14%-24%). Deep sequencing by Ion Torrent (Life Technologies) identified mutations in BTK^C481S and/or PLCG2, in 40 of 47 (85%) relapses. In 31 cases, BTK^C481S was the sole mutation. Mutational burdens varied among patients, but generally correlated with CLL progression in peripheral blood versus primarily nodal relapse.

At baseline, 172 (58%) of retrospective study participants had complex cytogenetics, 52% had del(13q), 40% had del(17p), and 21% had MYC abnormality. Median age was 65 years (range, 26-91 years) and 70% of patients were female. Multivariable analyses linked transformation to complex karyotype (hazard ratio, 5.0; 95% CI, 1.5-16.5) and MYC abnormality (HR, 2.5; 95% CI, 1.0-4.7), and linked progressive CLL to age younger than 65 years, complex karyotype, and del(17)(p13.1).

Richter transformation usually occurred within 2 years of starting ibrutinib and had a cumulative 4-year incidence of 10%, the investigators also reported. Patients survived a median of only 3.9 months after stopping ibrutinib because of transformation. The cumulative rate of progressive CLL was higher (19.1%), but early progression was rare, and patients who stopped ibrutinib because of progression survived longer (median, 22.7 months).

In the prospective study, all eight patients with BTK^C481S who had not yet clinically relapsed nonetheless had increasing frequency of this mutation over time, the investigators reported. Together, the findings confirm BTK and PLCG2 mutations as the key players in CLL resistance to ibrutinib, they stated. Perhaps most importantly, they reveal “a prolonged period of asymptomatic clonal expression” in CLL that precedes clinical relapse and provides a window of opportunity to target these cells with novel therapies in clinical trials, they wrote.

Given that ibrutinib was approved for use in relapsed CLL only 2 years ago, “We are likely just starting to see the first emergence of relapse in the community setting,” the researchers concluded. “Enhanced knowledge of both the molecular and clinical mechanisms of relapse may allow for strategic alterations in monitoring and management that could change the natural history of ibrutinib resistance.”

Funding sources included the D. Warren Brown Foundation, Mr. and Mrs. Michael Thomas, the Four Winds Foundation, the Leukemia and Lymphoma Society, Pelotonia, and the National Cancer Institute. Pharmacyclics also provided partial support. Dr. Woyach disclosed ties to Janssen, Acerta Pharma, Karyopharm Therapeutics, and MorphoSys, and a provisional patent related to ^C481S detection.

The number of outpatient visits for CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, results from a large analysis of national data showed.

“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” researchers led by Donovan T. Maust, MD, wrote in a research letter published online Feb. 13, 2017, in JAMA Internal Medicine. “Opioids have recently been included in a Beers measure of central nervous system polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the U.S. Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants.”

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dbrunk@frontlinemedcom.com

The number of outpatient visits for CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, results from a large analysis of national data showed.

“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” researchers led by Donovan T. Maust, MD, wrote in a research letter published online Feb. 13, 2017, in JAMA Internal Medicine. “Opioids have recently been included in a Beers measure of central nervous system polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the U.S. Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants.”

iStock/Thinkstock.com

dbrunk@frontlinemedcom.com

The number of outpatient visits for CNS polypharmacy by adults aged 65 and older more than doubled between 2004 and 2013, especially among those who reside in rural areas, results from a large analysis of national data showed.

“With each new revision of the Beers Criteria, the list of psychotropic medications considered potentially inappropriate in the elderly has grown,” researchers led by Donovan T. Maust, MD, wrote in a research letter published online Feb. 13, 2017, in JAMA Internal Medicine. “Opioids have recently been included in a Beers measure of central nervous system polypharmacy. Prescribing related drug combinations also received increased regulatory attention when the U.S. Food and Drug Administration recently ordered a black box warning to alert patients of serious risks, including death, caused by opioids coprescribed with CNS depressants.”

iStock/Thinkstock.com

dbrunk@frontlinemedcom.com

Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.

For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).

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Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.

For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).

lolostock/Thinkstock

Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.

For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).

lolostock/Thinkstock

BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.

The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.

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sworcester@frontlinemedcom.com

BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.

The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.

copyright kgtoh/Thinkstock

sworcester@frontlinemedcom.com

BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.

The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.

copyright kgtoh/Thinkstock

sworcester@frontlinemedcom.com

Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.

The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.

Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).

The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).

“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”

The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.

dbrunk@frontlinemedcom.com
 

Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.

The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.

Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).

The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).

“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”

The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.

dbrunk@frontlinemedcom.com
 

Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.

The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.

Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).

The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).

“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”

The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.

dbrunk@frontlinemedcom.com