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VIDEO: Is anastrozole or tamoxifen best for secondary prevention of DCIS?
SAN ANTONIO – Two large phase III randomized trials comparing anastrozole and tamoxifen for prevention of disease recurrence in postmenopausal women with ductal carcinoma in situ were presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Anthony Howell, professor of medical oncology at the University of Manchester, England, provides the key take-home lessons from the NSABP B-35 and IBIS-II DCIS trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Two large phase III randomized trials comparing anastrozole and tamoxifen for prevention of disease recurrence in postmenopausal women with ductal carcinoma in situ were presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Anthony Howell, professor of medical oncology at the University of Manchester, England, provides the key take-home lessons from the NSABP B-35 and IBIS-II DCIS trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Two large phase III randomized trials comparing anastrozole and tamoxifen for prevention of disease recurrence in postmenopausal women with ductal carcinoma in situ were presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Anthony Howell, professor of medical oncology at the University of Manchester, England, provides the key take-home lessons from the NSABP B-35 and IBIS-II DCIS trials.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2015
VIDEO: Beta-blocker prevented trastuzumab-related drop in LVEF
SAN ANTONIO – Prophylactic beta-blockade with bisoprolol during adjuvant trastuzumab therapy for HER2-positive breast cancer prevented trastuzumab-induced decline in left ventricular ejection fraction in a randomized trial.
In an interview at the San Antonio Breast Cancer Symposium, Dr. Edie Pituskin of the University of Alberta, Edmonton, explained why the double-blind, placebo-controlled MANTICORE trial may change clinical practice.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Prophylactic beta-blockade with bisoprolol during adjuvant trastuzumab therapy for HER2-positive breast cancer prevented trastuzumab-induced decline in left ventricular ejection fraction in a randomized trial.
In an interview at the San Antonio Breast Cancer Symposium, Dr. Edie Pituskin of the University of Alberta, Edmonton, explained why the double-blind, placebo-controlled MANTICORE trial may change clinical practice.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Prophylactic beta-blockade with bisoprolol during adjuvant trastuzumab therapy for HER2-positive breast cancer prevented trastuzumab-induced decline in left ventricular ejection fraction in a randomized trial.
In an interview at the San Antonio Breast Cancer Symposium, Dr. Edie Pituskin of the University of Alberta, Edmonton, explained why the double-blind, placebo-controlled MANTICORE trial may change clinical practice.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2015
EADV: Pursuing ‘clear’ in psoriasis worthwhile, expert says
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
COPENHAGEN – It is worthwhile to push harder for complete skin clearance in a psoriasis patient whose treatment regimen provides a Physician Global Assessment score of 1, or “almost clear,” according to Dr. Kristian Reich.
He presented an analysis of pooled data from the active treatment arms of three 12-week phase III clinical trials of the investigational interleukin-17 inhibitor brodalumab. The 1,260 patients with a static Physician Global Assessment (PGA) score of 1, or almost clear, at week 12 had significantly greater residual disease in terms of involved body surface area, fewer symptom-free days, and greater health-related quality of life impairment than did the 1,097 participants who achieved a static PGA of 0.
“These results suggest that clear versus almost clear represents meaningfully different levels of disease,” Dr. Reich of Dermatologikum Hamburg (Germany) said at the annual congress of the European Academy of Dermatology and Venereology.
The newer-generation biologics that target IL-17 or IL-23 provide a significantly greater rate of complete skin clearance than do the older anti–tumor necrosis factor biologic agents. But the newer biologics are also typically costlier and have a shorter safety record. So the question arises: Does the residual disease that defines a static PGA of 1 matter to patients in terms of quality of life and days free of symptoms? Or do they want even better results, if achievable? This is what Dr. Reich and his coworkers set out to answer.
Thirty percent of patients with a static PGA of 1 had clinically significant residual disease at week 12 as defined by a body surface area involvement of 6% or greater, as did 0.3% of those with a static PGA of 0. Fourteen percent of patients with a static PGA of 1 had a Dermatology Life Quality Index score of 6 or more, indicative of at least moderate impairment in quality of life, compared with 6.4% of psoriasis patients with a static PGA of 0.
Moreover, 42% of patients with a static PGA of 0 were 100% symptom free every day from week 10 to week 12 of the study as defined by a score of 0 on the eight-item Psoriasis Symptom Inventory, compared with 12% of patients with a static PGA of 1.
Dr. Reich reported receiving research support from Amgen, which funded the study.
AT THE EADV CONGRESS
Key clinical point: A Physician Global Assessment of “clear” is worth striving for in psoriasis patients because it represents a clinically important lesser level of disease than “almost clear.”
Major finding: Fourteen percent of psoriasis patients with an on-treatment physician assessment of “almost clear” had at least moderately impaired health care quality of life, compared with 6.4% of those rated “clear.”
Data source: A secondary pooled analysis of quality of life–related outcomes among psoriasis patients rated “clear” as opposed to “almost clear” at week 12 of three phase III double-blind randomized trials of the interleukin-17 inhibitor brodalumab.
Disclosures: The presenter reported receiving research support from Amgen, which sponsored the study.
EADV: Focus on non-UV triggers of melanoma
COPENHAGEN – Sunlight is recognized as the 800-pound gorilla of melanoma risk, with roughly 65% of all melanomas worldwide attributable to exposure to UV radiation. But what about the other 35%?
About 10% of melanomas are due to an inherited germline mutation, and new germline mutations are being discovered all the time. However, the incidence of melanoma has been rising steadily in industrialized countries since the 1950s, and genetic predisposition can’t explain that phenomenon. Environmental and lifestyle factors are likely to be involved. Indeed, melanomas arising from epigenetic modifications by extrinsic environmental and lifestyle factors other than UV exposure are drawing increasing research attention because of the potential for preventing the malignancy through avoidance of these risk factors, Dr. Veronique del Marmol said at the annual congress of the European Academy of Dermatology and Venereology.
One promising avenue of investigation focuses on microRNAs (miRs) as environmental drivers of melanoma risk. The miRs are important posttranscriptional regulators of gene expression. In particular, overexpression of miR-21 has been shown to accompany the transition of benign melanocytes into melanoma. miR-21 affects numerous genes critical to oncogenesis, including genes promoting sustained proliferation, angiogenesis, evasion from apoptosis, genetic instability, oxidative stress, and invasion and metastasis, as detailed recently [J Transl Med. 2015 Jun 27;13:202] by Dr. Bodo C. Melnik of the department of dermatology, environmental medicine, and health theory, University of Osnabrück (Germany).
Translational work by Dr. Melnik and others has shown that miR-21 expression is upregulated by several elements that investigators have long suspected are associated with an increased risk of melanoma, including smoking, air pollution, polychlorinated biphenyls and other noxious chemicals, chronic inflammation, a high-fat/high-sugar diet, and a sedentary lifestyle. Even cow’s milk has generated suspicion, since bovine miR-21 is identical to human miR-21, noted Dr. del Marmol, head of the department of dermatology at Erasmus Hospital in Brussels and chair of the pan-European Euromelanoma project.
Two noteworthy factors that have generated interest recently are coffee consumption, shown in a large observational study to protect against melanoma, and sildenafil (Viagra), which was shown in an analysis of 25,848 physicians enrolled in the Health Professionals’ Follow-Up Study to be associated with a 2.24-fold increased risk of subsequently developing melanoma during prospective follow-up (JAMA Intern Med. 2014 Jun;174[6]:964-70).
An association between increased risk of melanoma and the use of sildenafil or other phosphodiesterase-5 (PDE-5) inhibitors commonly used by men with erectile dysfunction is biologically plausible, according to Dr. del Marmol. Activation of oncogenic BRAF is a hallmark of 40%-60% of melanomas, and BRAF activation, like sildenafil use, downregulates phosphodiesterase-5A, which increases the invasiveness of melanoma cells.
The coffee connection was identified through an analysis of food frequency questionnaires completed by 447,357 non-Hispanic whites enrolled in the NIH-AARP Diet and Health Study, a prospective study developed at the National Cancer Institute.
During 4.3 million person-years of follow-up, 2,904 individuals were diagnosed with malignant melanoma. In a multivariate analysis, quaffing 4 or more cups of caffeinated coffee daily was associated with a 25% reduction in the risk of developing melanoma. Lesser consumption had no significant impact on melanoma risk (J Natl Cancer Inst. 2015 Jan 20;107[2]: pii: dju421. doi: 10.1093/jnci/dju421].
COPENHAGEN – Sunlight is recognized as the 800-pound gorilla of melanoma risk, with roughly 65% of all melanomas worldwide attributable to exposure to UV radiation. But what about the other 35%?
About 10% of melanomas are due to an inherited germline mutation, and new germline mutations are being discovered all the time. However, the incidence of melanoma has been rising steadily in industrialized countries since the 1950s, and genetic predisposition can’t explain that phenomenon. Environmental and lifestyle factors are likely to be involved. Indeed, melanomas arising from epigenetic modifications by extrinsic environmental and lifestyle factors other than UV exposure are drawing increasing research attention because of the potential for preventing the malignancy through avoidance of these risk factors, Dr. Veronique del Marmol said at the annual congress of the European Academy of Dermatology and Venereology.
One promising avenue of investigation focuses on microRNAs (miRs) as environmental drivers of melanoma risk. The miRs are important posttranscriptional regulators of gene expression. In particular, overexpression of miR-21 has been shown to accompany the transition of benign melanocytes into melanoma. miR-21 affects numerous genes critical to oncogenesis, including genes promoting sustained proliferation, angiogenesis, evasion from apoptosis, genetic instability, oxidative stress, and invasion and metastasis, as detailed recently [J Transl Med. 2015 Jun 27;13:202] by Dr. Bodo C. Melnik of the department of dermatology, environmental medicine, and health theory, University of Osnabrück (Germany).
Translational work by Dr. Melnik and others has shown that miR-21 expression is upregulated by several elements that investigators have long suspected are associated with an increased risk of melanoma, including smoking, air pollution, polychlorinated biphenyls and other noxious chemicals, chronic inflammation, a high-fat/high-sugar diet, and a sedentary lifestyle. Even cow’s milk has generated suspicion, since bovine miR-21 is identical to human miR-21, noted Dr. del Marmol, head of the department of dermatology at Erasmus Hospital in Brussels and chair of the pan-European Euromelanoma project.
Two noteworthy factors that have generated interest recently are coffee consumption, shown in a large observational study to protect against melanoma, and sildenafil (Viagra), which was shown in an analysis of 25,848 physicians enrolled in the Health Professionals’ Follow-Up Study to be associated with a 2.24-fold increased risk of subsequently developing melanoma during prospective follow-up (JAMA Intern Med. 2014 Jun;174[6]:964-70).
An association between increased risk of melanoma and the use of sildenafil or other phosphodiesterase-5 (PDE-5) inhibitors commonly used by men with erectile dysfunction is biologically plausible, according to Dr. del Marmol. Activation of oncogenic BRAF is a hallmark of 40%-60% of melanomas, and BRAF activation, like sildenafil use, downregulates phosphodiesterase-5A, which increases the invasiveness of melanoma cells.
The coffee connection was identified through an analysis of food frequency questionnaires completed by 447,357 non-Hispanic whites enrolled in the NIH-AARP Diet and Health Study, a prospective study developed at the National Cancer Institute.
During 4.3 million person-years of follow-up, 2,904 individuals were diagnosed with malignant melanoma. In a multivariate analysis, quaffing 4 or more cups of caffeinated coffee daily was associated with a 25% reduction in the risk of developing melanoma. Lesser consumption had no significant impact on melanoma risk (J Natl Cancer Inst. 2015 Jan 20;107[2]: pii: dju421. doi: 10.1093/jnci/dju421].
COPENHAGEN – Sunlight is recognized as the 800-pound gorilla of melanoma risk, with roughly 65% of all melanomas worldwide attributable to exposure to UV radiation. But what about the other 35%?
About 10% of melanomas are due to an inherited germline mutation, and new germline mutations are being discovered all the time. However, the incidence of melanoma has been rising steadily in industrialized countries since the 1950s, and genetic predisposition can’t explain that phenomenon. Environmental and lifestyle factors are likely to be involved. Indeed, melanomas arising from epigenetic modifications by extrinsic environmental and lifestyle factors other than UV exposure are drawing increasing research attention because of the potential for preventing the malignancy through avoidance of these risk factors, Dr. Veronique del Marmol said at the annual congress of the European Academy of Dermatology and Venereology.
One promising avenue of investigation focuses on microRNAs (miRs) as environmental drivers of melanoma risk. The miRs are important posttranscriptional regulators of gene expression. In particular, overexpression of miR-21 has been shown to accompany the transition of benign melanocytes into melanoma. miR-21 affects numerous genes critical to oncogenesis, including genes promoting sustained proliferation, angiogenesis, evasion from apoptosis, genetic instability, oxidative stress, and invasion and metastasis, as detailed recently [J Transl Med. 2015 Jun 27;13:202] by Dr. Bodo C. Melnik of the department of dermatology, environmental medicine, and health theory, University of Osnabrück (Germany).
Translational work by Dr. Melnik and others has shown that miR-21 expression is upregulated by several elements that investigators have long suspected are associated with an increased risk of melanoma, including smoking, air pollution, polychlorinated biphenyls and other noxious chemicals, chronic inflammation, a high-fat/high-sugar diet, and a sedentary lifestyle. Even cow’s milk has generated suspicion, since bovine miR-21 is identical to human miR-21, noted Dr. del Marmol, head of the department of dermatology at Erasmus Hospital in Brussels and chair of the pan-European Euromelanoma project.
Two noteworthy factors that have generated interest recently are coffee consumption, shown in a large observational study to protect against melanoma, and sildenafil (Viagra), which was shown in an analysis of 25,848 physicians enrolled in the Health Professionals’ Follow-Up Study to be associated with a 2.24-fold increased risk of subsequently developing melanoma during prospective follow-up (JAMA Intern Med. 2014 Jun;174[6]:964-70).
An association between increased risk of melanoma and the use of sildenafil or other phosphodiesterase-5 (PDE-5) inhibitors commonly used by men with erectile dysfunction is biologically plausible, according to Dr. del Marmol. Activation of oncogenic BRAF is a hallmark of 40%-60% of melanomas, and BRAF activation, like sildenafil use, downregulates phosphodiesterase-5A, which increases the invasiveness of melanoma cells.
The coffee connection was identified through an analysis of food frequency questionnaires completed by 447,357 non-Hispanic whites enrolled in the NIH-AARP Diet and Health Study, a prospective study developed at the National Cancer Institute.
During 4.3 million person-years of follow-up, 2,904 individuals were diagnosed with malignant melanoma. In a multivariate analysis, quaffing 4 or more cups of caffeinated coffee daily was associated with a 25% reduction in the risk of developing melanoma. Lesser consumption had no significant impact on melanoma risk (J Natl Cancer Inst. 2015 Jan 20;107[2]: pii: dju421. doi: 10.1093/jnci/dju421].
EXPERT ANALYSIS FROM THE EADV CONGRESS
EADV: Fresh insights into Gorlin syndrome
COPENHAGEN – A glimpse into the massive burden imposed upon patients with basal cell nevus syndrome (BCNS) is provided by the initial report from the first U.S. registry of patients affected with the disorder to include individuals who’ve tried the Hedgehog signaling pathway inhibitor vismodegib.
The first 94 patients (average age, 56 years) with BCNS to enroll in the prospective registry had a reported lifetime mean of 312 basal cell carcinomas (BCCs), Dr. Marieke Peters reported at the annual congress of the European Academy of Dermatology and Venereology.
The patients had an average of 36 new BCCs or other tumors in the previous 2 years, and 70% were categorized as having moderate to severe BCNS (also known as Gorlin syndrome), as defined by more than 10 new BCCs during that time period.
Most (94%) of tumors were on sun-exposed areas. Patients reported a lifetime mean of 202 surgical excisions, according to Dr. Peters of Catharina Hospital Eindhoven, the Netherlands.
The median age at diagnosis of BCNS was 15 years, and most patients were diagnosed clinically. Only 26% had undergone genetic testing for PTCH1. (The syndrome is caused by mutations in the PTCH1 gene). Sixty-two percent of subjects reported a family history of BCNS.
Other abnormalities associated with BCNS were common: Eighty percent of patients had jaw cysts, 82% had palmer pitting, 50% had various bone abnormalities, 21% reported ovarian fibromas, 4% reported medulloblastomas, and 4% had other tumors.
Fifty-seven percent of patients had tried vismodegib (Erivedge). However, only 15% were currently on the drug at enrollment; the rest had discontinued it, mainly because of side effects; less frequently because of loss of efficacy due to the development of new mutations. The chief side effects were nausea, vomiting, and diarrhea; less frequent side effects were weight loss, fatigue, muscle cramps, and alopecia, according to the dermatologist.
Gorlin syndrome is a rare autosomal dominant disorder caused mainly by mutations in the PTCH1 gene. The U.S. registry is directed by investigators at Children’s Hospital Oakland Research Institute and Stanford (Calif.) University.
The patient questionnaire used in the BCNS registry is available at https://redcap.stanford.edu/surveys/?s=7MWW9E37ND. For more information about the registry, contact Dr. Ervin Epstein, at eepstein@chori.org.
Dr. Peters reported having no financial conflicts regarding her report. At the time of the EADV meeting, she was a dermatology resident at the Academic Medical Center, Amsterdam.
*This story was updated 12/15/2015.
COPENHAGEN – A glimpse into the massive burden imposed upon patients with basal cell nevus syndrome (BCNS) is provided by the initial report from the first U.S. registry of patients affected with the disorder to include individuals who’ve tried the Hedgehog signaling pathway inhibitor vismodegib.
The first 94 patients (average age, 56 years) with BCNS to enroll in the prospective registry had a reported lifetime mean of 312 basal cell carcinomas (BCCs), Dr. Marieke Peters reported at the annual congress of the European Academy of Dermatology and Venereology.
The patients had an average of 36 new BCCs or other tumors in the previous 2 years, and 70% were categorized as having moderate to severe BCNS (also known as Gorlin syndrome), as defined by more than 10 new BCCs during that time period.
Most (94%) of tumors were on sun-exposed areas. Patients reported a lifetime mean of 202 surgical excisions, according to Dr. Peters of Catharina Hospital Eindhoven, the Netherlands.
The median age at diagnosis of BCNS was 15 years, and most patients were diagnosed clinically. Only 26% had undergone genetic testing for PTCH1. (The syndrome is caused by mutations in the PTCH1 gene). Sixty-two percent of subjects reported a family history of BCNS.
Other abnormalities associated with BCNS were common: Eighty percent of patients had jaw cysts, 82% had palmer pitting, 50% had various bone abnormalities, 21% reported ovarian fibromas, 4% reported medulloblastomas, and 4% had other tumors.
Fifty-seven percent of patients had tried vismodegib (Erivedge). However, only 15% were currently on the drug at enrollment; the rest had discontinued it, mainly because of side effects; less frequently because of loss of efficacy due to the development of new mutations. The chief side effects were nausea, vomiting, and diarrhea; less frequent side effects were weight loss, fatigue, muscle cramps, and alopecia, according to the dermatologist.
Gorlin syndrome is a rare autosomal dominant disorder caused mainly by mutations in the PTCH1 gene. The U.S. registry is directed by investigators at Children’s Hospital Oakland Research Institute and Stanford (Calif.) University.
The patient questionnaire used in the BCNS registry is available at https://redcap.stanford.edu/surveys/?s=7MWW9E37ND. For more information about the registry, contact Dr. Ervin Epstein, at eepstein@chori.org.
Dr. Peters reported having no financial conflicts regarding her report. At the time of the EADV meeting, she was a dermatology resident at the Academic Medical Center, Amsterdam.
*This story was updated 12/15/2015.
COPENHAGEN – A glimpse into the massive burden imposed upon patients with basal cell nevus syndrome (BCNS) is provided by the initial report from the first U.S. registry of patients affected with the disorder to include individuals who’ve tried the Hedgehog signaling pathway inhibitor vismodegib.
The first 94 patients (average age, 56 years) with BCNS to enroll in the prospective registry had a reported lifetime mean of 312 basal cell carcinomas (BCCs), Dr. Marieke Peters reported at the annual congress of the European Academy of Dermatology and Venereology.
The patients had an average of 36 new BCCs or other tumors in the previous 2 years, and 70% were categorized as having moderate to severe BCNS (also known as Gorlin syndrome), as defined by more than 10 new BCCs during that time period.
Most (94%) of tumors were on sun-exposed areas. Patients reported a lifetime mean of 202 surgical excisions, according to Dr. Peters of Catharina Hospital Eindhoven, the Netherlands.
The median age at diagnosis of BCNS was 15 years, and most patients were diagnosed clinically. Only 26% had undergone genetic testing for PTCH1. (The syndrome is caused by mutations in the PTCH1 gene). Sixty-two percent of subjects reported a family history of BCNS.
Other abnormalities associated with BCNS were common: Eighty percent of patients had jaw cysts, 82% had palmer pitting, 50% had various bone abnormalities, 21% reported ovarian fibromas, 4% reported medulloblastomas, and 4% had other tumors.
Fifty-seven percent of patients had tried vismodegib (Erivedge). However, only 15% were currently on the drug at enrollment; the rest had discontinued it, mainly because of side effects; less frequently because of loss of efficacy due to the development of new mutations. The chief side effects were nausea, vomiting, and diarrhea; less frequent side effects were weight loss, fatigue, muscle cramps, and alopecia, according to the dermatologist.
Gorlin syndrome is a rare autosomal dominant disorder caused mainly by mutations in the PTCH1 gene. The U.S. registry is directed by investigators at Children’s Hospital Oakland Research Institute and Stanford (Calif.) University.
The patient questionnaire used in the BCNS registry is available at https://redcap.stanford.edu/surveys/?s=7MWW9E37ND. For more information about the registry, contact Dr. Ervin Epstein, at eepstein@chori.org.
Dr. Peters reported having no financial conflicts regarding her report. At the time of the EADV meeting, she was a dermatology resident at the Academic Medical Center, Amsterdam.
*This story was updated 12/15/2015.
AT THE EADV CONGRESS
Key clinical point: Gorlin syndrome imposes an impressively heavy burden on affected patients.
Major finding: Patients with basal cell nevus syndrome reported a lifetime mean of 312 basal cell carcinomas and 202 surgical excisions.
Data source: The initial report from a prospective U.S. registry of patients with basal cell nevus syndrome, which is still enrolling participants.
Disclosures: The presenter reported having no financial conflicts regarding her study.
VIDEO: Mastectomy plus reconstruction has highest complication rates of all early BC treatment options
SAN ANTONIO – Mastectomy with reconstruction is the outlier in terms of complication rates and cost among options for local therapy for early breast cancer, according to a large observational study presented at the San Antonio Breast Cancer Symposium.
Complication rates during the first 2 years after diagnosis were roughly twice as high for mastectomy plus reconstruction, compared with lumpectomy with whole breast irradiation. Moreover, average total procedural and complication costs were $23,000 greater for women aged 65 years or younger who opted for mastectomy plus reconstruction than for those who chose lumpectomy plus whole breast irradiation. These fresh insights into the trade-offs involved in local treatment options should prove useful in oncologists’ discussions with newly diagnosed patients, as well as for payers, as Dr. Benjamin D. Smith of University of Texas M.D. Anderson Cancer Center, Houston, explains in an interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Mastectomy with reconstruction is the outlier in terms of complication rates and cost among options for local therapy for early breast cancer, according to a large observational study presented at the San Antonio Breast Cancer Symposium.
Complication rates during the first 2 years after diagnosis were roughly twice as high for mastectomy plus reconstruction, compared with lumpectomy with whole breast irradiation. Moreover, average total procedural and complication costs were $23,000 greater for women aged 65 years or younger who opted for mastectomy plus reconstruction than for those who chose lumpectomy plus whole breast irradiation. These fresh insights into the trade-offs involved in local treatment options should prove useful in oncologists’ discussions with newly diagnosed patients, as well as for payers, as Dr. Benjamin D. Smith of University of Texas M.D. Anderson Cancer Center, Houston, explains in an interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Mastectomy with reconstruction is the outlier in terms of complication rates and cost among options for local therapy for early breast cancer, according to a large observational study presented at the San Antonio Breast Cancer Symposium.
Complication rates during the first 2 years after diagnosis were roughly twice as high for mastectomy plus reconstruction, compared with lumpectomy with whole breast irradiation. Moreover, average total procedural and complication costs were $23,000 greater for women aged 65 years or younger who opted for mastectomy plus reconstruction than for those who chose lumpectomy plus whole breast irradiation. These fresh insights into the trade-offs involved in local treatment options should prove useful in oncologists’ discussions with newly diagnosed patients, as well as for payers, as Dr. Benjamin D. Smith of University of Texas M.D. Anderson Cancer Center, Houston, explains in an interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2015
VIDEO: Triple-negative breast cancer outcomes boosted by adding carboplatin to neoadjuvant chemo
SAN ANTONIO – Adding weekly carboplatin to 18 weeks of anthracycline/taxane-based neoadjuvant chemotherapy markedly improved disease-free survival in patients with triple-negative breast cancer, according to updated results from the GeparSixto trial presented at the San Antonio Breast Cancer Symposium.
Dr. Gunter von Minckwitz, president of the German Breast Group, explains in an interview that the nearly 50% reduction in the risk of disease relapse at 3 years seen in the phase II trial has converted him and his coinvestigators to routine use of add-on carboplatin in triple-negative breast cancer patients on neoadjuvant chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Adding weekly carboplatin to 18 weeks of anthracycline/taxane-based neoadjuvant chemotherapy markedly improved disease-free survival in patients with triple-negative breast cancer, according to updated results from the GeparSixto trial presented at the San Antonio Breast Cancer Symposium.
Dr. Gunter von Minckwitz, president of the German Breast Group, explains in an interview that the nearly 50% reduction in the risk of disease relapse at 3 years seen in the phase II trial has converted him and his coinvestigators to routine use of add-on carboplatin in triple-negative breast cancer patients on neoadjuvant chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Adding weekly carboplatin to 18 weeks of anthracycline/taxane-based neoadjuvant chemotherapy markedly improved disease-free survival in patients with triple-negative breast cancer, according to updated results from the GeparSixto trial presented at the San Antonio Breast Cancer Symposium.
Dr. Gunter von Minckwitz, president of the German Breast Group, explains in an interview that the nearly 50% reduction in the risk of disease relapse at 3 years seen in the phase II trial has converted him and his coinvestigators to routine use of add-on carboplatin in triple-negative breast cancer patients on neoadjuvant chemotherapy.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2015
ACC/AHA risk estimator underpredicts in HIV+ individuals
ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.
That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.
Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.
The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.
That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.
“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.
Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.
Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.
Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.
Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.
The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.
Dr. Feinstein reported having no financial conflicts regarding this study.
ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.
That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.
Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.
The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.
That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.
“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.
Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.
Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.
Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.
Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.
The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.
Dr. Feinstein reported having no financial conflicts regarding this study.
ORLANDO – The 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator isn’t reliably applicable to HIV-positive adults in its present form because it consistently underpredicts their MI risk, Dr. Michael J. Feinstein reported at the American Heart Association scientific sessions.
That’s the bad news. The good news is that “a simple, data-derived refit of the pooled cohort equations may improve the model’s performance in HIV-positive individuals,” said Dr. Feinstein of Northwestern University, Chicago.
Tweaking the risk calculator to enhance its accuracy in the HIV-positive population is particularly important because this population is growing in size and aging. And as Dr. Feinstein and coinvestigators showed in another study presented at the AHA meeting, the proportion of deaths due to cardiovascular disease in HIV-positive adults is shooting upward as they live longer because of treatment advances.
The investigators’ analysis of data from the Centers for Disease Control and Prevention national Wonder database showed that the proportion of deaths due to cardiovascular disease more than doubled between 1999 and 2013. Meanwhile, proportionate cardiovascular disease mortality declined by 22% in the general population and by 28% among individuals with inflammatory polyarthropathies.
That the ACC/AHA risk calculator in its present form doesn’t perform adequately in HIV-positive individuals hadn’t previously been shown, but it doesn’t really come as a surprise, according to Dr. Feinstein. After all, it’s known that this population is at 1.5- to 2-fold increased risk for MI and roughly 5-fold increased risk for sudden cardiac death, compared to the general population, where the risk calculator works best.
“Most data suggest that even in the setting of optimally treated HIV and undetectable viral load there’s still an underlying viral reservoir that appears to be driving inflammation and atherothrombotic and even nonatherothrombotic events in this population,” he said.
Dr. Feinstein and coworkers evaluated the 2013 ACC/AHA risk calculator in 11,901 HIV-positive black or white adults enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) database for whom 5-year follow-up was available; 52% of the subjects were aged 40 or older at baseline.
Running each of these nearly 12,000 subjects through the risk calculator, the predicted result was that 103 of them would have an acute MI during the 5-year follow-up period. In reality, 132 MIs were observed. The discrepancy between the risk calculator predictions and observed MI rates was greatest in the 63% of HIV-positive subjects deemed at low risk, with an estimated 10-year risk of atherosclerotic cardiovascular disease of less than 5%.
Among white men, the risk calculator was remarkably consistent in underpredicting MIs. Regardless of whether the risk calculator put their estimated 10-year risk at less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, or at least 10%, the actual observed MI rates were 67%-68% greater across the board than predicted.
Dr. Feinstein and coworkers refit the ACC/AHA risk calculator on a trial basis by incorporating variables related to HIV-positivity into the risk equations. Then they reanalyzed the tool’s performance in the same nearly 12,000 HIV-infected subjects. They found the discrimination and calibration of the revised risk equations improved substantially and met the standard of “acceptable” by statisticians’ standards.
The next step in this ongoing CNICS project will be to validate the provisionally refit risk calculator’s performance in a separate database of HIV-infected adults with adjudicated MIs. If the results are again positive, it will be a relatively straightforward matter to introduce the revisions into the ACC/AHA risk calculator, particularly since the senior coinvestigator in this project is Dr. Donald M. Lloyd-Jones, also of Northwestern University, who played a central role in developing the 2013 risk calculator.
Dr. Feinstein reported having no financial conflicts regarding this study.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: The 2013 ACC/AHA risk estimator needs a tune-up before it can be reliably applied to HIV-infected adults.
Major finding: Observed rates of acute MI over time in HIV-positive white men were 67%-68% higher than predicted by the 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator regardless of whether the men were deemed at low, intermediate, or high baseline risk.
Data source: A study comparing the predicted number of acute MIs in a population of nearly 12,000 HIV-positive adults over a 5-year period as determined via the 2013 ACC/AHA atherosclerotic cardiovascular disease risk calculator with the actual observed number of adjudicated MIs.
Disclosures: The study was conducted free of commercial support. The presenter reported having no financial conflicts of interest.
AHA: Ezetimibe reduces ischemic stroke risk
ORLANDO – The combination of ezetimibe/simvastatin significantly reduced the risk of nonhemorrhagic stroke compared with simvastatin alone, with a particularly striking benefit seen in patients with prior history of stroke, in a new analysis from the landmark IMPROVE-IT trial.
“We believe these data support the use of intensive lipid lowering therapy, which includes ezetimibe to prevent ischemic stroke,” Dr. Stephen D. Wiviott said in reporting the findings at the American Heart Association scientific sessions.
He presented a prespecified secondary analysis from IMPROVE-IT, a double-blind study in which 18,144 patients on background optimal medical management were randomized post–acute coronary syndrome to simvastatin/ezetimibe at 40/10 mg/day (Vytorin) or simvastatin (Zocor) at 40 mg/day. At a median of 6 years of follow-up, the primary composite cardiovascular outcome was significantly reduced by 6% in the dual-therapy group compared with statin monotherapy, with a number-needed-to-treat (NNT) of 50, as previously reported (N Engl J Med. 2015 Jun 18;372[25]:2387-97).
The impetus for the prespecified stroke analysis was that up until IMPROVE-IT, no LDL cholesterol–lowering therapy other than statins had ever been shown to protect against stroke. The Cholesterol Trialists’ Collaboration meta-analysis, involving roughly 173,000 subjects, previously showed that statin therapy reduces ischemic stroke risk by 20% per 1 mmol/L of LDL lowering (Lancet. 2012 Aug 11;380[9841]:581-90). The question was, could add-on ezetimibe decrease stroke risk even further?
Stroke occurred in 641 patients during follow-up. As adjudicated by independent neurologists, 82% of the strokes were nonhemorrhagic, 16% were hemorrhagic, and 2% were unknown. The 14% relative risk reduction in overall stroke with simvastatin/ezetimibe compared with simvastatin, with rates of 4.2% versus 4.8%, just missed achieving statistical significance (P = .052). A significant 21% reduction in nonhemorrhagic strokes was seen with dual therapy, where the incidence during follow-up was 3.4%, compared with 4.1% with simvastatin alone, but this effect was dampened by a numeric albeit statistically nonsignificant absolute 0.2% increase in hemorrhagic strokes in the simvastatin/ezetimibe group.
Far more impressive was the stroke-prevention benefit of simvastatin/ezetimibe among the 1,071 subjects with prior stroke or TIA at baseline. Their nonhemorrhagic stroke rate during follow-up was 10.2% with simvastatin/ezetimibe versus 18.8% with simvastatin alone, for a 40% relative risk reduction favoring dual lipid-lowering therapy and an NNT of about 20. Again, there was no significant difference in hemorrhagic stroke between the two treatment arms, noted Dr. Wiviott of Brigham and Womens Hospital, Boston.
The stroke-prevention benefit achieved by adding ezetimibe to simvastatin was seen regardless of patient age, gender, renal function, baseline LDL cholesterol level, or other prespecified subcategories.
IMPROVE-IT was sponsored by Merck. Dr. Wiviott reported receiving research grants from Merck, AstraZeneca, and Eisai and serving as a consultant to nine pharmaceutical companies.
ORLANDO – The combination of ezetimibe/simvastatin significantly reduced the risk of nonhemorrhagic stroke compared with simvastatin alone, with a particularly striking benefit seen in patients with prior history of stroke, in a new analysis from the landmark IMPROVE-IT trial.
“We believe these data support the use of intensive lipid lowering therapy, which includes ezetimibe to prevent ischemic stroke,” Dr. Stephen D. Wiviott said in reporting the findings at the American Heart Association scientific sessions.
He presented a prespecified secondary analysis from IMPROVE-IT, a double-blind study in which 18,144 patients on background optimal medical management were randomized post–acute coronary syndrome to simvastatin/ezetimibe at 40/10 mg/day (Vytorin) or simvastatin (Zocor) at 40 mg/day. At a median of 6 years of follow-up, the primary composite cardiovascular outcome was significantly reduced by 6% in the dual-therapy group compared with statin monotherapy, with a number-needed-to-treat (NNT) of 50, as previously reported (N Engl J Med. 2015 Jun 18;372[25]:2387-97).
The impetus for the prespecified stroke analysis was that up until IMPROVE-IT, no LDL cholesterol–lowering therapy other than statins had ever been shown to protect against stroke. The Cholesterol Trialists’ Collaboration meta-analysis, involving roughly 173,000 subjects, previously showed that statin therapy reduces ischemic stroke risk by 20% per 1 mmol/L of LDL lowering (Lancet. 2012 Aug 11;380[9841]:581-90). The question was, could add-on ezetimibe decrease stroke risk even further?
Stroke occurred in 641 patients during follow-up. As adjudicated by independent neurologists, 82% of the strokes were nonhemorrhagic, 16% were hemorrhagic, and 2% were unknown. The 14% relative risk reduction in overall stroke with simvastatin/ezetimibe compared with simvastatin, with rates of 4.2% versus 4.8%, just missed achieving statistical significance (P = .052). A significant 21% reduction in nonhemorrhagic strokes was seen with dual therapy, where the incidence during follow-up was 3.4%, compared with 4.1% with simvastatin alone, but this effect was dampened by a numeric albeit statistically nonsignificant absolute 0.2% increase in hemorrhagic strokes in the simvastatin/ezetimibe group.
Far more impressive was the stroke-prevention benefit of simvastatin/ezetimibe among the 1,071 subjects with prior stroke or TIA at baseline. Their nonhemorrhagic stroke rate during follow-up was 10.2% with simvastatin/ezetimibe versus 18.8% with simvastatin alone, for a 40% relative risk reduction favoring dual lipid-lowering therapy and an NNT of about 20. Again, there was no significant difference in hemorrhagic stroke between the two treatment arms, noted Dr. Wiviott of Brigham and Womens Hospital, Boston.
The stroke-prevention benefit achieved by adding ezetimibe to simvastatin was seen regardless of patient age, gender, renal function, baseline LDL cholesterol level, or other prespecified subcategories.
IMPROVE-IT was sponsored by Merck. Dr. Wiviott reported receiving research grants from Merck, AstraZeneca, and Eisai and serving as a consultant to nine pharmaceutical companies.
ORLANDO – The combination of ezetimibe/simvastatin significantly reduced the risk of nonhemorrhagic stroke compared with simvastatin alone, with a particularly striking benefit seen in patients with prior history of stroke, in a new analysis from the landmark IMPROVE-IT trial.
“We believe these data support the use of intensive lipid lowering therapy, which includes ezetimibe to prevent ischemic stroke,” Dr. Stephen D. Wiviott said in reporting the findings at the American Heart Association scientific sessions.
He presented a prespecified secondary analysis from IMPROVE-IT, a double-blind study in which 18,144 patients on background optimal medical management were randomized post–acute coronary syndrome to simvastatin/ezetimibe at 40/10 mg/day (Vytorin) or simvastatin (Zocor) at 40 mg/day. At a median of 6 years of follow-up, the primary composite cardiovascular outcome was significantly reduced by 6% in the dual-therapy group compared with statin monotherapy, with a number-needed-to-treat (NNT) of 50, as previously reported (N Engl J Med. 2015 Jun 18;372[25]:2387-97).
The impetus for the prespecified stroke analysis was that up until IMPROVE-IT, no LDL cholesterol–lowering therapy other than statins had ever been shown to protect against stroke. The Cholesterol Trialists’ Collaboration meta-analysis, involving roughly 173,000 subjects, previously showed that statin therapy reduces ischemic stroke risk by 20% per 1 mmol/L of LDL lowering (Lancet. 2012 Aug 11;380[9841]:581-90). The question was, could add-on ezetimibe decrease stroke risk even further?
Stroke occurred in 641 patients during follow-up. As adjudicated by independent neurologists, 82% of the strokes were nonhemorrhagic, 16% were hemorrhagic, and 2% were unknown. The 14% relative risk reduction in overall stroke with simvastatin/ezetimibe compared with simvastatin, with rates of 4.2% versus 4.8%, just missed achieving statistical significance (P = .052). A significant 21% reduction in nonhemorrhagic strokes was seen with dual therapy, where the incidence during follow-up was 3.4%, compared with 4.1% with simvastatin alone, but this effect was dampened by a numeric albeit statistically nonsignificant absolute 0.2% increase in hemorrhagic strokes in the simvastatin/ezetimibe group.
Far more impressive was the stroke-prevention benefit of simvastatin/ezetimibe among the 1,071 subjects with prior stroke or TIA at baseline. Their nonhemorrhagic stroke rate during follow-up was 10.2% with simvastatin/ezetimibe versus 18.8% with simvastatin alone, for a 40% relative risk reduction favoring dual lipid-lowering therapy and an NNT of about 20. Again, there was no significant difference in hemorrhagic stroke between the two treatment arms, noted Dr. Wiviott of Brigham and Womens Hospital, Boston.
The stroke-prevention benefit achieved by adding ezetimibe to simvastatin was seen regardless of patient age, gender, renal function, baseline LDL cholesterol level, or other prespecified subcategories.
IMPROVE-IT was sponsored by Merck. Dr. Wiviott reported receiving research grants from Merck, AstraZeneca, and Eisai and serving as a consultant to nine pharmaceutical companies.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point: Intensive lipid-lowering therapy that incorporates ezetimibe provides enhanced protection against ischemic stroke.
Major finding: In patients with a baseline history of stroke who were on simvastatin/ezetimibe after an acute coronary syndrome, the risk of nonhemorrhagic stroke during 6 years of follow-up was reduced by 40%, compared with lipid-lowering via simvastatin alone.
Data source: A prespecified secondary analysis of stroke incidence during a median 6 years of follow-up in the double-blind, randomized, 18,144-patient IMPROVE-IT trial.
Disclosures: Merck sponsored the study. The presenter reported receiving a research grant from Merck and serving as a consultant to numerous pharmaceutical companies.
VIDEO: Win-win with denosumab as adjuvant therapy for post-menopausal breast cancer
SAN ANTONIO – Adding denosumab to adjuvant aromatase inhibitor therapy, not only reduced risk of fracture, but also improved disease-free survival for postmenopausal patients with early-stage, hormone receptor–positive breast cancer, according to results presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Michael Gnant, professor of surgery at the Medical University of Vienna, discusses the phase III ABCSG-18 clinical trial, and why he will now be prescribing denosumab to HR-positive breast cancer patients who are receiving adjuvant aromatase inhibitor therapy, regardless of their bone health status.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Adding denosumab to adjuvant aromatase inhibitor therapy, not only reduced risk of fracture, but also improved disease-free survival for postmenopausal patients with early-stage, hormone receptor–positive breast cancer, according to results presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Michael Gnant, professor of surgery at the Medical University of Vienna, discusses the phase III ABCSG-18 clinical trial, and why he will now be prescribing denosumab to HR-positive breast cancer patients who are receiving adjuvant aromatase inhibitor therapy, regardless of their bone health status.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Adding denosumab to adjuvant aromatase inhibitor therapy, not only reduced risk of fracture, but also improved disease-free survival for postmenopausal patients with early-stage, hormone receptor–positive breast cancer, according to results presented at the San Antonio Breast Cancer Symposium.
In an interview, Dr. Michael Gnant, professor of surgery at the Medical University of Vienna, discusses the phase III ABCSG-18 clinical trial, and why he will now be prescribing denosumab to HR-positive breast cancer patients who are receiving adjuvant aromatase inhibitor therapy, regardless of their bone health status.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2015
