Nonmelanoma Skin Cancer

I have taken beta-blockers for nearly 30 years to combat a non–life-threatening but very disconcerting supraventricular arrhythmia. Also being fair skinned and having suffered through many a blistering sunburn in my youth, I was excited to read the most recent publication regarding the relationship between beta-blocker ingestion and survival from melanoma by De Giorgi et al (Mayo Clin Proc. 2013;88:1196-1203). The Italian investigators collected data from all melanoma patients diagnosed in the dermatology department at the University of Florence (1993-2009). After excluding patients who presented with metastatic disease, they then compared the courses of the remaining patients based on whether or not they had been prescribed beta-blockers for at least 1 year before or after their cutaneous melanoma diagnosis. Of 741 consecutive patients who fit the retrospective study criteria, 79 (11%) had been taking beta-blockers and the remaining 662 (89%) had not been taking beta-blockers.

An analysis based on the multivariate Cox model indicated that the beta-blocker group had improved overall survival after a median follow-up of 4.2 years (P=.005). Looked at in another way, significantly more patients in the untreated group (8%) than the beta-blocker group (3%) experienced disease progression or death (P<.001). The “protective” effect of beta-blockers was so striking that it could be quantified; for each year of beta-blocker use, the risk for death was reduced by 38%. More notable was the fact that the beneficial effect of beta-blocker administration was consistent, even among patients with inherently unfavorable prognostic factors, such as advanced age, thicker lesions, higher frequency of mitoses and ulceration, and nodular melanoma subtype. This large study confirms the results of a much smaller study (N=121) published by the same group in 2011 (Arch Intern Med. 2011;171:779-781).

What’s the issue?

Why might this phenomenon occur? Perhaps blocking sympathetic nervous system neurotransmitters might help avoid the suspected immunosuppression that accompanies stress. Sympathetic neurotransmitters also are known to interact with molecular pathways implicated in abnormal cellular replication, such as the p38/MAPK pathway. Thus, blunting the effects of epinephrine and norepinephrine by blocking some of their receptors might produce a salutatory benefit in the cancer (in this case, melanoma) patient.

Before we all rush out and give all our melanoma patients daily doses of metoprolol, however, De Giorgi et al noted in the most recent study that about two-thirds of the patients were already taking a beta-blocker when their melanoma was diagnosed. Although this study suggests that beta-blockers reduce the risk for recurrence and disease-specific mortality, these drugs clearly do not prevent melanoma in the first place. Furthermore, it should be noted that the number of melanoma patients receiving beta-blockers was small, and conclusions should always be tempered in a retrospective study. The authors duly admit that their investigation indicates the strong need for a truly randomized prospective clinical trial. Of course, administration of beta-blockers is not a totally benign endeavor, as serious hypotension and/or bradycardia may occur, leading to syncope or even worse problems. Finally, the evidence of beta-blocker benefit in melanoma patients is contradictory! A Dutch cohort of 709 melanoma patients recently was studied (Eur J Cancer. 2013;49:3863-3871); this set of investigators found that exposure to beta-blockers did not impact overall melanoma survival regardless of the timing, duration, or dosage of beta-blocker use. In summary, therefore, we still need to determine many things about the relationship between beta-blockers and melanoma survival. That is, if there is a relationship at all. What do you think?

We want to know your views! Tell us what you think.

I have taken beta-blockers for nearly 30 years to combat a non–life-threatening but very disconcerting supraventricular arrhythmia. Also being fair skinned and having suffered through many a blistering sunburn in my youth, I was excited to read the most recent publication regarding the relationship between beta-blocker ingestion and survival from melanoma by De Giorgi et al (Mayo Clin Proc. 2013;88:1196-1203). The Italian investigators collected data from all melanoma patients diagnosed in the dermatology department at the University of Florence (1993-2009). After excluding patients who presented with metastatic disease, they then compared the courses of the remaining patients based on whether or not they had been prescribed beta-blockers for at least 1 year before or after their cutaneous melanoma diagnosis. Of 741 consecutive patients who fit the retrospective study criteria, 79 (11%) had been taking beta-blockers and the remaining 662 (89%) had not been taking beta-blockers.

An analysis based on the multivariate Cox model indicated that the beta-blocker group had improved overall survival after a median follow-up of 4.2 years (P=.005). Looked at in another way, significantly more patients in the untreated group (8%) than the beta-blocker group (3%) experienced disease progression or death (P<.001). The “protective” effect of beta-blockers was so striking that it could be quantified; for each year of beta-blocker use, the risk for death was reduced by 38%. More notable was the fact that the beneficial effect of beta-blocker administration was consistent, even among patients with inherently unfavorable prognostic factors, such as advanced age, thicker lesions, higher frequency of mitoses and ulceration, and nodular melanoma subtype. This large study confirms the results of a much smaller study (N=121) published by the same group in 2011 (Arch Intern Med. 2011;171:779-781).

What’s the issue?

Why might this phenomenon occur? Perhaps blocking sympathetic nervous system neurotransmitters might help avoid the suspected immunosuppression that accompanies stress. Sympathetic neurotransmitters also are known to interact with molecular pathways implicated in abnormal cellular replication, such as the p38/MAPK pathway. Thus, blunting the effects of epinephrine and norepinephrine by blocking some of their receptors might produce a salutatory benefit in the cancer (in this case, melanoma) patient.

Before we all rush out and give all our melanoma patients daily doses of metoprolol, however, De Giorgi et al noted in the most recent study that about two-thirds of the patients were already taking a beta-blocker when their melanoma was diagnosed. Although this study suggests that beta-blockers reduce the risk for recurrence and disease-specific mortality, these drugs clearly do not prevent melanoma in the first place. Furthermore, it should be noted that the number of melanoma patients receiving beta-blockers was small, and conclusions should always be tempered in a retrospective study. The authors duly admit that their investigation indicates the strong need for a truly randomized prospective clinical trial. Of course, administration of beta-blockers is not a totally benign endeavor, as serious hypotension and/or bradycardia may occur, leading to syncope or even worse problems. Finally, the evidence of beta-blocker benefit in melanoma patients is contradictory! A Dutch cohort of 709 melanoma patients recently was studied (Eur J Cancer. 2013;49:3863-3871); this set of investigators found that exposure to beta-blockers did not impact overall melanoma survival regardless of the timing, duration, or dosage of beta-blocker use. In summary, therefore, we still need to determine many things about the relationship between beta-blockers and melanoma survival. That is, if there is a relationship at all. What do you think?

We want to know your views! Tell us what you think.

I have taken beta-blockers for nearly 30 years to combat a non–life-threatening but very disconcerting supraventricular arrhythmia. Also being fair skinned and having suffered through many a blistering sunburn in my youth, I was excited to read the most recent publication regarding the relationship between beta-blocker ingestion and survival from melanoma by De Giorgi et al (Mayo Clin Proc. 2013;88:1196-1203). The Italian investigators collected data from all melanoma patients diagnosed in the dermatology department at the University of Florence (1993-2009). After excluding patients who presented with metastatic disease, they then compared the courses of the remaining patients based on whether or not they had been prescribed beta-blockers for at least 1 year before or after their cutaneous melanoma diagnosis. Of 741 consecutive patients who fit the retrospective study criteria, 79 (11%) had been taking beta-blockers and the remaining 662 (89%) had not been taking beta-blockers.

An analysis based on the multivariate Cox model indicated that the beta-blocker group had improved overall survival after a median follow-up of 4.2 years (P=.005). Looked at in another way, significantly more patients in the untreated group (8%) than the beta-blocker group (3%) experienced disease progression or death (P<.001). The “protective” effect of beta-blockers was so striking that it could be quantified; for each year of beta-blocker use, the risk for death was reduced by 38%. More notable was the fact that the beneficial effect of beta-blocker administration was consistent, even among patients with inherently unfavorable prognostic factors, such as advanced age, thicker lesions, higher frequency of mitoses and ulceration, and nodular melanoma subtype. This large study confirms the results of a much smaller study (N=121) published by the same group in 2011 (Arch Intern Med. 2011;171:779-781).

What’s the issue?

Why might this phenomenon occur? Perhaps blocking sympathetic nervous system neurotransmitters might help avoid the suspected immunosuppression that accompanies stress. Sympathetic neurotransmitters also are known to interact with molecular pathways implicated in abnormal cellular replication, such as the p38/MAPK pathway. Thus, blunting the effects of epinephrine and norepinephrine by blocking some of their receptors might produce a salutatory benefit in the cancer (in this case, melanoma) patient.

Before we all rush out and give all our melanoma patients daily doses of metoprolol, however, De Giorgi et al noted in the most recent study that about two-thirds of the patients were already taking a beta-blocker when their melanoma was diagnosed. Although this study suggests that beta-blockers reduce the risk for recurrence and disease-specific mortality, these drugs clearly do not prevent melanoma in the first place. Furthermore, it should be noted that the number of melanoma patients receiving beta-blockers was small, and conclusions should always be tempered in a retrospective study. The authors duly admit that their investigation indicates the strong need for a truly randomized prospective clinical trial. Of course, administration of beta-blockers is not a totally benign endeavor, as serious hypotension and/or bradycardia may occur, leading to syncope or even worse problems. Finally, the evidence of beta-blocker benefit in melanoma patients is contradictory! A Dutch cohort of 709 melanoma patients recently was studied (Eur J Cancer. 2013;49:3863-3871); this set of investigators found that exposure to beta-blockers did not impact overall melanoma survival regardless of the timing, duration, or dosage of beta-blocker use. In summary, therefore, we still need to determine many things about the relationship between beta-blockers and melanoma survival. That is, if there is a relationship at all. What do you think?

We want to know your views! Tell us what you think.

Squamous cell carcinoma (SCC) on sun-exposed sites following prolonged immunosuppression is one of the main long-term complications of allogeneic transplantations. In an article published in the Journal of Clinical Investigation (2013;123:3797-3801), the investigators demonstrated that the SCC tumor cells from a renal transplant patient had the donor genotype and harbored a TP53 (tumor-suppressing p53) mutation in codon 175; in addition, the same TP53 mutation had previously been documented 7 years earlier in p53⁺ cells in the renal tubules from a kidney graft biopsy. The observations in this patient provide evidence that the kidney donor can contribute to subsequent SCCs in renal transplant recipients.

What’s the issue?

Donor contribution to the malignant epithelium of cutaneous cancer in organ transplant recipients has several important implications. First, this observation provides additional insight into the initiation and progression of tumor carcinogenesis. Second, because there is longer survival of patients following renal transplant and therefore a prolonged duration of immunosuppression in these individuals, the development of long-term complications such as SCC of sun-exposed skin may be greater. Third, should genetic profiling of kidneys from potential donors to screen for cancer-associated mutations be performed? And fourth, is this phenomenon restricted only to patients receiving kidneys or might it be a possible complication in the recipients of other organs such as hearts, lungs, or even faces?

We want to know your views! Tell us what you think.

Squamous cell carcinoma (SCC) on sun-exposed sites following prolonged immunosuppression is one of the main long-term complications of allogeneic transplantations. In an article published in the Journal of Clinical Investigation (2013;123:3797-3801), the investigators demonstrated that the SCC tumor cells from a renal transplant patient had the donor genotype and harbored a TP53 (tumor-suppressing p53) mutation in codon 175; in addition, the same TP53 mutation had previously been documented 7 years earlier in p53⁺ cells in the renal tubules from a kidney graft biopsy. The observations in this patient provide evidence that the kidney donor can contribute to subsequent SCCs in renal transplant recipients.

What’s the issue?

Donor contribution to the malignant epithelium of cutaneous cancer in organ transplant recipients has several important implications. First, this observation provides additional insight into the initiation and progression of tumor carcinogenesis. Second, because there is longer survival of patients following renal transplant and therefore a prolonged duration of immunosuppression in these individuals, the development of long-term complications such as SCC of sun-exposed skin may be greater. Third, should genetic profiling of kidneys from potential donors to screen for cancer-associated mutations be performed? And fourth, is this phenomenon restricted only to patients receiving kidneys or might it be a possible complication in the recipients of other organs such as hearts, lungs, or even faces?

We want to know your views! Tell us what you think.

Squamous cell carcinoma (SCC) on sun-exposed sites following prolonged immunosuppression is one of the main long-term complications of allogeneic transplantations. In an article published in the Journal of Clinical Investigation (2013;123:3797-3801), the investigators demonstrated that the SCC tumor cells from a renal transplant patient had the donor genotype and harbored a TP53 (tumor-suppressing p53) mutation in codon 175; in addition, the same TP53 mutation had previously been documented 7 years earlier in p53⁺ cells in the renal tubules from a kidney graft biopsy. The observations in this patient provide evidence that the kidney donor can contribute to subsequent SCCs in renal transplant recipients.

What’s the issue?

Donor contribution to the malignant epithelium of cutaneous cancer in organ transplant recipients has several important implications. First, this observation provides additional insight into the initiation and progression of tumor carcinogenesis. Second, because there is longer survival of patients following renal transplant and therefore a prolonged duration of immunosuppression in these individuals, the development of long-term complications such as SCC of sun-exposed skin may be greater. Third, should genetic profiling of kidneys from potential donors to screen for cancer-associated mutations be performed? And fourth, is this phenomenon restricted only to patients receiving kidneys or might it be a possible complication in the recipients of other organs such as hearts, lungs, or even faces?

We want to know your views! Tell us what you think.

ISTANBUL – Vismodegib-treated patients with locally advanced basal cell carcinoma showed triple the median response duration after 24 months’ follow-up beyond the primary analysis of the drug, Dr. Luc Dirix reported at the annual congress of the European Academy of Dermatology and Venereology.

Vismodegib, the first-in-class oral medication for treatment of advanced BCC, showed a greatly improved duration of response and no new safety signals in updated results from the ERIVANCE BCC trial, which earlier had earned the drug marketing approval from the Food and Drug Administration and European Medicines Agency.

After 24 months beyond what was included in the primary analysis of ERIVANCE BCC (N. Engl. J. Med. 2012;366:2171-9), the median duration of response by investigator assessment in patients with locally advanced BCC increased from 7.6 to 26.2 months, and increased from 7.6 to 12.9 months in those with metastatic BCC.

"The main new fact is that the median duration of response has increased importantly. That’s a very impressive improvement in disease control, especially in patients with locally advanced disease. It’s a major change from what you’ll find in the New England Journal of Medicine publication," observed Dr. Dirix of Sint-AugustinusHospital, Antwerp, Belgium.

Dr. Dirix reported that, with the additional 24 months of follow-up in the ERIVANCE BCC study, median progression-free survival now stands at 9.3 months in the group with metastatic BCC and 12.9 months in those with locally advanced disease. The objective response rate, which was 43% in patients with locally advanced BCC and 30% in those with metastatic disease in the primary analysis, hasn’t changed significantly with the additional follow-up, he said.

The median overall survival was 33 months. Twelve of the original 33 patients in the cohort with metastatic BCC have died of progressive disease, as have 4 of 63 with locally advanced BCC.

The ERIVANCE BCC trial is an open-label, phase II study in which participants were placed on vismodegib at 150 mg once daily until the occurrence of disease progression, intolerable toxicity, or patient request to withdraw. At the latest follow-up, only 13% of the original study population remained on the drug, Dr. Dirix said. Half of the patients with metastatic BCC who discontinued the drug did so because of disease progression, but only 16% of those with locally advanced BCC stopped treatment. Instead, side effects were the main reason locally advanced BCC patients discontinued therapy.

"The additional 24 months of follow-up didn’t result in any new safety signal, but there are numerous side effects, especially muscle spasms, alopecia, dysgeusia, and others, mostly mild or moderate," said Dr. Dirix.

An estimated 1.6 million new cases of BCC were diagnosed in the United States in 2006, making it the most common form of cancer in the country. Most BCCs are readily treated. However, some cases can progress to locally advanced or metastatic BCC, a disfiguring and potentially life-threatening condition that is not treatable surgically or via radiation therapy, and for which no effective therapy existed before. Vismodegib (Erivedge) provides an oral drug option that works as an inhibitor of the hedgehog pathway, which plays a key role in the pathogenesis of most BCCs.

With vismodegib intended as lifelong treatment in patients with advanced BCC, and considerable research interest in exploring the drug in other forms of BCC, reliable safety data are needed. Also at the EADV Congress, Dr. Rainer Kunstfeld presented new safety information in an interim analysis from an ongoing study known as STEVIE (Safety Events in Vismodegib), the largest study of the hedgehog pathway inhibitor. His report included the first 300 of a planned 1,200 patients with advanced BCC to be placed on vismodegib.

The data underscore the point that advanced BCC is primarily a disease of the elderly. The mean age of the 278 patients with locally advanced BCC is 70 years, and 65 years in the 22 with metastatic BCC. The median treatment duration as of the data cutoff for this analysis was 5.8 months.

Forty-five percent of patients in the locally advanced BCC group have discontinued treatment, as have 32% of those with metastatic disease, Dr. Kunstfeld said. The reasons differed for the two groups. Discontinuation due to disease progression or death was more than twice as common in patients with metastatic BCC. Patients with locally advanced disease were much more likely to halt treatment because of adverse events.

Ninety-three percent of STEVIE participants experienced at least one adverse event. Roughly two-thirds of these side effects were mild or moderate – that is, grade 1 or 2 – while the remainder were grade 3. The incidence of the most common adverse events were muscle spasms in 59% of participants, alopecia in 49%, distorted sense of taste in 41%, loss of the sense of taste in 26%, asthenia in 23%, and weight loss in 16%. These data were consistent with the safety profile seen in the ERIVANCE BCC study, observed Dr. Kunstfeld, a dermatologist at the Medical University of Vienna.

Of the 251 patients with tumor assessments available to date, more than 95% showed some degree of therapeutic benefit. A complete response was documented in 17.5% of patients, a partial response in 39.8%, and 39% had stable disease. Fewer than 3% have experienced disease progression during this early follow-up period.

The ERIVANCE BCC and STEVIE studies are funded by Genentech. Dr. Dirix and Dr. Kunstfeld reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ISTANBUL – Vismodegib-treated patients with locally advanced basal cell carcinoma showed triple the median response duration after 24 months’ follow-up beyond the primary analysis of the drug, Dr. Luc Dirix reported at the annual congress of the European Academy of Dermatology and Venereology.

Vismodegib, the first-in-class oral medication for treatment of advanced BCC, showed a greatly improved duration of response and no new safety signals in updated results from the ERIVANCE BCC trial, which earlier had earned the drug marketing approval from the Food and Drug Administration and European Medicines Agency.

After 24 months beyond what was included in the primary analysis of ERIVANCE BCC (N. Engl. J. Med. 2012;366:2171-9), the median duration of response by investigator assessment in patients with locally advanced BCC increased from 7.6 to 26.2 months, and increased from 7.6 to 12.9 months in those with metastatic BCC.

"The main new fact is that the median duration of response has increased importantly. That’s a very impressive improvement in disease control, especially in patients with locally advanced disease. It’s a major change from what you’ll find in the New England Journal of Medicine publication," observed Dr. Dirix of Sint-AugustinusHospital, Antwerp, Belgium.

Dr. Dirix reported that, with the additional 24 months of follow-up in the ERIVANCE BCC study, median progression-free survival now stands at 9.3 months in the group with metastatic BCC and 12.9 months in those with locally advanced disease. The objective response rate, which was 43% in patients with locally advanced BCC and 30% in those with metastatic disease in the primary analysis, hasn’t changed significantly with the additional follow-up, he said.

The median overall survival was 33 months. Twelve of the original 33 patients in the cohort with metastatic BCC have died of progressive disease, as have 4 of 63 with locally advanced BCC.

The ERIVANCE BCC trial is an open-label, phase II study in which participants were placed on vismodegib at 150 mg once daily until the occurrence of disease progression, intolerable toxicity, or patient request to withdraw. At the latest follow-up, only 13% of the original study population remained on the drug, Dr. Dirix said. Half of the patients with metastatic BCC who discontinued the drug did so because of disease progression, but only 16% of those with locally advanced BCC stopped treatment. Instead, side effects were the main reason locally advanced BCC patients discontinued therapy.

"The additional 24 months of follow-up didn’t result in any new safety signal, but there are numerous side effects, especially muscle spasms, alopecia, dysgeusia, and others, mostly mild or moderate," said Dr. Dirix.

An estimated 1.6 million new cases of BCC were diagnosed in the United States in 2006, making it the most common form of cancer in the country. Most BCCs are readily treated. However, some cases can progress to locally advanced or metastatic BCC, a disfiguring and potentially life-threatening condition that is not treatable surgically or via radiation therapy, and for which no effective therapy existed before. Vismodegib (Erivedge) provides an oral drug option that works as an inhibitor of the hedgehog pathway, which plays a key role in the pathogenesis of most BCCs.

With vismodegib intended as lifelong treatment in patients with advanced BCC, and considerable research interest in exploring the drug in other forms of BCC, reliable safety data are needed. Also at the EADV Congress, Dr. Rainer Kunstfeld presented new safety information in an interim analysis from an ongoing study known as STEVIE (Safety Events in Vismodegib), the largest study of the hedgehog pathway inhibitor. His report included the first 300 of a planned 1,200 patients with advanced BCC to be placed on vismodegib.

The data underscore the point that advanced BCC is primarily a disease of the elderly. The mean age of the 278 patients with locally advanced BCC is 70 years, and 65 years in the 22 with metastatic BCC. The median treatment duration as of the data cutoff for this analysis was 5.8 months.

Forty-five percent of patients in the locally advanced BCC group have discontinued treatment, as have 32% of those with metastatic disease, Dr. Kunstfeld said. The reasons differed for the two groups. Discontinuation due to disease progression or death was more than twice as common in patients with metastatic BCC. Patients with locally advanced disease were much more likely to halt treatment because of adverse events.

Ninety-three percent of STEVIE participants experienced at least one adverse event. Roughly two-thirds of these side effects were mild or moderate – that is, grade 1 or 2 – while the remainder were grade 3. The incidence of the most common adverse events were muscle spasms in 59% of participants, alopecia in 49%, distorted sense of taste in 41%, loss of the sense of taste in 26%, asthenia in 23%, and weight loss in 16%. These data were consistent with the safety profile seen in the ERIVANCE BCC study, observed Dr. Kunstfeld, a dermatologist at the Medical University of Vienna.

Of the 251 patients with tumor assessments available to date, more than 95% showed some degree of therapeutic benefit. A complete response was documented in 17.5% of patients, a partial response in 39.8%, and 39% had stable disease. Fewer than 3% have experienced disease progression during this early follow-up period.

The ERIVANCE BCC and STEVIE studies are funded by Genentech. Dr. Dirix and Dr. Kunstfeld reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ISTANBUL – Vismodegib-treated patients with locally advanced basal cell carcinoma showed triple the median response duration after 24 months’ follow-up beyond the primary analysis of the drug, Dr. Luc Dirix reported at the annual congress of the European Academy of Dermatology and Venereology.

Vismodegib, the first-in-class oral medication for treatment of advanced BCC, showed a greatly improved duration of response and no new safety signals in updated results from the ERIVANCE BCC trial, which earlier had earned the drug marketing approval from the Food and Drug Administration and European Medicines Agency.

After 24 months beyond what was included in the primary analysis of ERIVANCE BCC (N. Engl. J. Med. 2012;366:2171-9), the median duration of response by investigator assessment in patients with locally advanced BCC increased from 7.6 to 26.2 months, and increased from 7.6 to 12.9 months in those with metastatic BCC.

"The main new fact is that the median duration of response has increased importantly. That’s a very impressive improvement in disease control, especially in patients with locally advanced disease. It’s a major change from what you’ll find in the New England Journal of Medicine publication," observed Dr. Dirix of Sint-AugustinusHospital, Antwerp, Belgium.

Dr. Dirix reported that, with the additional 24 months of follow-up in the ERIVANCE BCC study, median progression-free survival now stands at 9.3 months in the group with metastatic BCC and 12.9 months in those with locally advanced disease. The objective response rate, which was 43% in patients with locally advanced BCC and 30% in those with metastatic disease in the primary analysis, hasn’t changed significantly with the additional follow-up, he said.

The median overall survival was 33 months. Twelve of the original 33 patients in the cohort with metastatic BCC have died of progressive disease, as have 4 of 63 with locally advanced BCC.

The ERIVANCE BCC trial is an open-label, phase II study in which participants were placed on vismodegib at 150 mg once daily until the occurrence of disease progression, intolerable toxicity, or patient request to withdraw. At the latest follow-up, only 13% of the original study population remained on the drug, Dr. Dirix said. Half of the patients with metastatic BCC who discontinued the drug did so because of disease progression, but only 16% of those with locally advanced BCC stopped treatment. Instead, side effects were the main reason locally advanced BCC patients discontinued therapy.

"The additional 24 months of follow-up didn’t result in any new safety signal, but there are numerous side effects, especially muscle spasms, alopecia, dysgeusia, and others, mostly mild or moderate," said Dr. Dirix.

An estimated 1.6 million new cases of BCC were diagnosed in the United States in 2006, making it the most common form of cancer in the country. Most BCCs are readily treated. However, some cases can progress to locally advanced or metastatic BCC, a disfiguring and potentially life-threatening condition that is not treatable surgically or via radiation therapy, and for which no effective therapy existed before. Vismodegib (Erivedge) provides an oral drug option that works as an inhibitor of the hedgehog pathway, which plays a key role in the pathogenesis of most BCCs.

With vismodegib intended as lifelong treatment in patients with advanced BCC, and considerable research interest in exploring the drug in other forms of BCC, reliable safety data are needed. Also at the EADV Congress, Dr. Rainer Kunstfeld presented new safety information in an interim analysis from an ongoing study known as STEVIE (Safety Events in Vismodegib), the largest study of the hedgehog pathway inhibitor. His report included the first 300 of a planned 1,200 patients with advanced BCC to be placed on vismodegib.

The data underscore the point that advanced BCC is primarily a disease of the elderly. The mean age of the 278 patients with locally advanced BCC is 70 years, and 65 years in the 22 with metastatic BCC. The median treatment duration as of the data cutoff for this analysis was 5.8 months.

Forty-five percent of patients in the locally advanced BCC group have discontinued treatment, as have 32% of those with metastatic disease, Dr. Kunstfeld said. The reasons differed for the two groups. Discontinuation due to disease progression or death was more than twice as common in patients with metastatic BCC. Patients with locally advanced disease were much more likely to halt treatment because of adverse events.

Ninety-three percent of STEVIE participants experienced at least one adverse event. Roughly two-thirds of these side effects were mild or moderate – that is, grade 1 or 2 – while the remainder were grade 3. The incidence of the most common adverse events were muscle spasms in 59% of participants, alopecia in 49%, distorted sense of taste in 41%, loss of the sense of taste in 26%, asthenia in 23%, and weight loss in 16%. These data were consistent with the safety profile seen in the ERIVANCE BCC study, observed Dr. Kunstfeld, a dermatologist at the Medical University of Vienna.

Of the 251 patients with tumor assessments available to date, more than 95% showed some degree of therapeutic benefit. A complete response was documented in 17.5% of patients, a partial response in 39.8%, and 39% had stable disease. Fewer than 3% have experienced disease progression during this early follow-up period.

The ERIVANCE BCC and STEVIE studies are funded by Genentech. Dr. Dirix and Dr. Kunstfeld reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com