Head & Neck/Thyroid Cancers

SEATTLE – Sentinel lymph node biopsy in patients with head or neck desmoplastic melanoma is positive only 6% of the time, and it doesn’t change the risk of recurrence.

Although sentinel lymph node biopsy (SLNB) is routine in more common forms of cutaneous melanoma, findings from a retrospective case-control study suggest that it’s “not really necessary” for desmoplastic melanoma (DM) of the head or neck, said lead investigator Dylan Roden, MD, of the department of otolaryngology, New York University. General surgeons have pretty much come to that conclusion for DM elsewhere on the body, but it hasn’t been shown before for neck and head lesions, he said.

DM, an invasive form of melanoma in which malignant cells are surrounded by fibrous tissue, accounts for maybe 2% of cutaneous melanomas, with half or so presenting on the head or neck. The reason SLNB is of less use than with other melanomas is that DM “doesn’t often spread through the lymphatics. It’s not that patients won’t ever have metastases, but maybe it will be through the blood. Removing a lymph node won’t necessarily” detect it, Dr. Roden said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Forgoing SLNB has the added benefit of shaving an hour and a half or more off surgery, which is important since DM patients tend to be older, he added.

The NYU team matched 32 of their cases with 60 controls with more common superficial spreading or nodular melanoma of the head and neck, based on age, gender, ulceration status, and tumor stage. Mean tumor thickness in both groups was more than 4 mm.

SLNB was performed in 16 DM patients (50%) and 36 control patients (60%); it was positive in one DM patient (6.3%) versus 8 of 28 controls with reported results (28.6%).

Eleven DM patients (34%) had a recurrence, which was less frequent then in controls, where 33 patients (55%) had a recurrence (P = .05). “SNLB did not change the risk of overall or regional recurrence” in DM, Dr. Roden said.

Recurrence was more than twice as likely in control patients (odds ratio, 2.33; P = .06). Meanwhile, recurrence in DM was linked to perineural invasion (P = .02), but not ulceration status (P = .12) or mitoses (P = .40).

DM patients also had better 5-year overall survival (79% versus 62%) and disease-free survival (70% versus 42%; P for both = .06). In general, DM “has a more favorable prognosis,” Dr. Roden said.

Cases and controls were in their mid-60s, on average, and most were men. Ulceration was present in about a quarter of patients. Mitosis was more common in superficial spreading and nodular patients (92% versus 53%; P less than .001), while perineural invasion was more common in DM (40% versus 7%; P less than.001).

Although outcomes were more favorable for DM, previous studies have found a higher rate of sentinel lymph node metastases – above 20% – for DM lesions with mixed, rather than pure, pathology. The 6.3% positive SLNB rate at NYU is more in line with what’s been reported before for pure lesions. The team plans to look into the matter.

There was no outside funding for the work, and Dr. Roden had no disclosures.

[email protected]

SEATTLE – Sentinel lymph node biopsy in patients with head or neck desmoplastic melanoma is positive only 6% of the time, and it doesn’t change the risk of recurrence.

Although sentinel lymph node biopsy (SLNB) is routine in more common forms of cutaneous melanoma, findings from a retrospective case-control study suggest that it’s “not really necessary” for desmoplastic melanoma (DM) of the head or neck, said lead investigator Dylan Roden, MD, of the department of otolaryngology, New York University. General surgeons have pretty much come to that conclusion for DM elsewhere on the body, but it hasn’t been shown before for neck and head lesions, he said.

DM, an invasive form of melanoma in which malignant cells are surrounded by fibrous tissue, accounts for maybe 2% of cutaneous melanomas, with half or so presenting on the head or neck. The reason SLNB is of less use than with other melanomas is that DM “doesn’t often spread through the lymphatics. It’s not that patients won’t ever have metastases, but maybe it will be through the blood. Removing a lymph node won’t necessarily” detect it, Dr. Roden said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Forgoing SLNB has the added benefit of shaving an hour and a half or more off surgery, which is important since DM patients tend to be older, he added.

The NYU team matched 32 of their cases with 60 controls with more common superficial spreading or nodular melanoma of the head and neck, based on age, gender, ulceration status, and tumor stage. Mean tumor thickness in both groups was more than 4 mm.

SLNB was performed in 16 DM patients (50%) and 36 control patients (60%); it was positive in one DM patient (6.3%) versus 8 of 28 controls with reported results (28.6%).

Eleven DM patients (34%) had a recurrence, which was less frequent then in controls, where 33 patients (55%) had a recurrence (P = .05). “SNLB did not change the risk of overall or regional recurrence” in DM, Dr. Roden said.

Recurrence was more than twice as likely in control patients (odds ratio, 2.33; P = .06). Meanwhile, recurrence in DM was linked to perineural invasion (P = .02), but not ulceration status (P = .12) or mitoses (P = .40).

DM patients also had better 5-year overall survival (79% versus 62%) and disease-free survival (70% versus 42%; P for both = .06). In general, DM “has a more favorable prognosis,” Dr. Roden said.

Cases and controls were in their mid-60s, on average, and most were men. Ulceration was present in about a quarter of patients. Mitosis was more common in superficial spreading and nodular patients (92% versus 53%; P less than .001), while perineural invasion was more common in DM (40% versus 7%; P less than.001).

Although outcomes were more favorable for DM, previous studies have found a higher rate of sentinel lymph node metastases – above 20% – for DM lesions with mixed, rather than pure, pathology. The 6.3% positive SLNB rate at NYU is more in line with what’s been reported before for pure lesions. The team plans to look into the matter.

There was no outside funding for the work, and Dr. Roden had no disclosures.

[email protected]

SEATTLE – Sentinel lymph node biopsy in patients with head or neck desmoplastic melanoma is positive only 6% of the time, and it doesn’t change the risk of recurrence.

Although sentinel lymph node biopsy (SLNB) is routine in more common forms of cutaneous melanoma, findings from a retrospective case-control study suggest that it’s “not really necessary” for desmoplastic melanoma (DM) of the head or neck, said lead investigator Dylan Roden, MD, of the department of otolaryngology, New York University. General surgeons have pretty much come to that conclusion for DM elsewhere on the body, but it hasn’t been shown before for neck and head lesions, he said.

DM, an invasive form of melanoma in which malignant cells are surrounded by fibrous tissue, accounts for maybe 2% of cutaneous melanomas, with half or so presenting on the head or neck. The reason SLNB is of less use than with other melanomas is that DM “doesn’t often spread through the lymphatics. It’s not that patients won’t ever have metastases, but maybe it will be through the blood. Removing a lymph node won’t necessarily” detect it, Dr. Roden said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Forgoing SLNB has the added benefit of shaving an hour and a half or more off surgery, which is important since DM patients tend to be older, he added.

The NYU team matched 32 of their cases with 60 controls with more common superficial spreading or nodular melanoma of the head and neck, based on age, gender, ulceration status, and tumor stage. Mean tumor thickness in both groups was more than 4 mm.

SLNB was performed in 16 DM patients (50%) and 36 control patients (60%); it was positive in one DM patient (6.3%) versus 8 of 28 controls with reported results (28.6%).

Eleven DM patients (34%) had a recurrence, which was less frequent then in controls, where 33 patients (55%) had a recurrence (P = .05). “SNLB did not change the risk of overall or regional recurrence” in DM, Dr. Roden said.

Recurrence was more than twice as likely in control patients (odds ratio, 2.33; P = .06). Meanwhile, recurrence in DM was linked to perineural invasion (P = .02), but not ulceration status (P = .12) or mitoses (P = .40).

DM patients also had better 5-year overall survival (79% versus 62%) and disease-free survival (70% versus 42%; P for both = .06). In general, DM “has a more favorable prognosis,” Dr. Roden said.

Cases and controls were in their mid-60s, on average, and most were men. Ulceration was present in about a quarter of patients. Mitosis was more common in superficial spreading and nodular patients (92% versus 53%; P less than .001), while perineural invasion was more common in DM (40% versus 7%; P less than.001).

Although outcomes were more favorable for DM, previous studies have found a higher rate of sentinel lymph node metastases – above 20% – for DM lesions with mixed, rather than pure, pathology. The 6.3% positive SLNB rate at NYU is more in line with what’s been reported before for pure lesions. The team plans to look into the matter.

There was no outside funding for the work, and Dr. Roden had no disclosures.

[email protected]

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

SEATTLE – Adjunct testosterone improved short-term cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial from the University of Texas Medical Branch, Galveston.

The finding suggests that testosterone might counteract the cardiotoxic effects of chemotherapy, reducing “the incidence of chemotherapy-induced remodeling. It might also have rehabilitation implications and make patients better surgical candidates. Further investigation is warranted,” said investigator Albert Chamberlain, MD, an endocrine research fellow at the university. Although the results were positive, follow-up was short; years-long data are needed to know if testosterone really protects the heart from chemotherapy damage.

Dr. Chamberlain’s team looked into the issue because “many current chemotherapy drug classes have cardiotoxicity that progresses subclinically for a long time” before problems emerge. “Testosterone is known to cause vasodilation in both large and resistance arteries,” which might help prevent damage. “With that in mind, we decided to” investigate testosterone’s impact on cardiac performance during chemotherapy, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

Five women and one man were randomized to weekly intramuscular 100 mg testosterone injections for 7 weeks; six men and four women were randomized to placebo injections. They were all recently diagnosed with stage IIIB, IV, or recurrent head and neck cancer, or cervical cancer, and were undergoing concomitant standard-of-care chemotherapy or chemoradiation. Cardiac function was measured blindly by transthoracic echocardiogram at baseline and the end of the study.

The testosterone group had significantly improved stroke volumes (+18.2% versus –2.6%, P = 0.01), ejection fractions (+6.2% versus –1.8%, P = 0.02), and cardiac output (+1402.2 mL/min versus –16.8mL/min, P = 0.011). Heart rate, arterial pressure, end-diastolic volume, and end-systolic volume remained unchanged in both groups, so the improved systolic function was attributed to reduced vascular resistance in the testosterone group (–26.5% versus +3.9% in the placebo group, P = 0.001).

Systolic improvements remained as cardiac index increased 27.6% in the testosterone group versus 2.8% in the placebo group. Testosterone didn’t seem to have any negative impacts on diastolic function. A placebo patient had a stroke, but there were no other adverse events in the study.

Although improved stroke volume is likely due to the reduced afterload, “increased contractility cannot be eliminated as a potential contributing factor. End diastolic volume remained unchanged in both groups, [suggesting] that preload is unlikely to be the mechanism for increased stroke volume,” Dr. Chamberlain said.

This study was funded by the National Cancer Institute. Dr. Chamberlain reported having no relevant disclosures.

[email protected]

The Food and Drug Administration has granted a priority review for expanded use of nivolumab for patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), based on results of Checkmate-141.

CheckMate-141 was stopped early in January 2016 after the study met its primary endpoint of improved overall survival in SCCHN patients receiving nivolumab after platinum-based therapy, compared to investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab).

The FDA is expected to act on the review by Nov. 11, 2016, according to a written statement from Bristol-Myers Squib, makers of nivolumab.

The PD-1 immune checkpoint inhibitor, marketed as Opdivo, was also granted breakthrough therapy designation by the FDA for the treatment of unresectable locally advanced or metastatic urothelial carcinoma that has progressed during or following a platinum-based regimen, according to another written statement from Bristol-Myers Squibb. This is the sixth breakthrough therapy designation for nivolumab.

The breakthrough therapy designation in bladder cancer is based on the results of the phase II CA209-275 trial and other supportive data.

[email protected]

On Twitter @jessnicolecraig

The Food and Drug Administration has granted a priority review for expanded use of nivolumab for patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), based on results of Checkmate-141.

CheckMate-141 was stopped early in January 2016 after the study met its primary endpoint of improved overall survival in SCCHN patients receiving nivolumab after platinum-based therapy, compared to investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab).

The FDA is expected to act on the review by Nov. 11, 2016, according to a written statement from Bristol-Myers Squib, makers of nivolumab.

The PD-1 immune checkpoint inhibitor, marketed as Opdivo, was also granted breakthrough therapy designation by the FDA for the treatment of unresectable locally advanced or metastatic urothelial carcinoma that has progressed during or following a platinum-based regimen, according to another written statement from Bristol-Myers Squibb. This is the sixth breakthrough therapy designation for nivolumab.

The breakthrough therapy designation in bladder cancer is based on the results of the phase II CA209-275 trial and other supportive data.

[email protected]

On Twitter @jessnicolecraig

The Food and Drug Administration has granted a priority review for expanded use of nivolumab for patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), based on results of Checkmate-141.

CheckMate-141 was stopped early in January 2016 after the study met its primary endpoint of improved overall survival in SCCHN patients receiving nivolumab after platinum-based therapy, compared to investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab).

The FDA is expected to act on the review by Nov. 11, 2016, according to a written statement from Bristol-Myers Squib, makers of nivolumab.

The PD-1 immune checkpoint inhibitor, marketed as Opdivo, was also granted breakthrough therapy designation by the FDA for the treatment of unresectable locally advanced or metastatic urothelial carcinoma that has progressed during or following a platinum-based regimen, according to another written statement from Bristol-Myers Squibb. This is the sixth breakthrough therapy designation for nivolumab.

The breakthrough therapy designation in bladder cancer is based on the results of the phase II CA209-275 trial and other supportive data.

[email protected]

On Twitter @jessnicolecraig

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

[email protected]

On Twitter @NikolaidesLaura

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

[email protected]

On Twitter @NikolaidesLaura

Stand Up To Cancer is calling for proposals to investigate additional uses for nivolumab, ipilimumab, elotuzumab, and urelumab, as part of a new researcher-industry collaborative program.

As many as four projects will be funded by Bristol-Myers Squibb, maker of the four agents, in the range of $1 million to $3 million each, according to a written statement from the American Association for Cancer Research (AACR).

The company will provide access to the three drugs already approved for the treatement of various cancers –nivolumab, ipilimumab, and elotuzumab– and to urelumab, an investigational agent that is currently in early clinical trials.

Proposals can include the study of one or more of the products, alone or in combination with other treatments, and may include products from other companies, as well as explore potential new uses for the drug(s), AACR said in the statement.

Nivolumab (Opdivo) is currently approved to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin lymphoma; Ipilimumab (Yervoy) is approved to treat melanoma; and elotuzumab (Empliciti) is approved to treat multiple myeloma, in conjunction with other drugs. Urelumab is being evaluated as a treatment for a range of cancers, including some hematological cancers, advanced colorectal cancer, and head and neck cancers.

The Stand Up To Cancer (SU2C) Catalyst program was launched in April to “use funding and materials from the pharmaceutical, biotechnology, diagnostic, and medical devices industries to accelerate research on cancer prevention, detection, and treatment,” according to a written statement from SU2C. Founding collaborators in addition to Bristol-Myers Squibb include Merck and Genentech.

The Catalyst projects must follow the SU2C model be carried out by a collaborative team, and be designed to accelerate the clinical use of therapeutic agents within the 3-year term of the grant, and to deliver near-term patient benefit.

The Request for Proposal for the Bristol-Myers Squibb agents is available at proposalCENTRAL, with proposals due by noon ET Monday, Aug. 15.

[email protected]

On Twitter @NikolaidesLaura

Up to 6% of patients with head and neck squamous cell carcinoma (SCC) also have synchronous second primary cancers (SPCs). However, the synchronous cancers may be missed in a usual examination that relies on CT and MRI scans.

Related: Complex Malignancies: A Diagnostic and Therapeutic Trilemma

Clinicians from Odense University Hospital in Denmark report on a patient who presented with only tongue pain as a symptom but was found to have 4 SPCs. The CT and MRI results were inconclusive due to artifacts from metal dental fillings. However, a positron emission tomography (PET)-CT scan “easily revealed” the 3 coinciding malignancies because of their increased metabolic activity, the authors say.

Their patient had 4 primary cancers: 1 SCC on the left side of the tongue, 1 in the fold between the tongue and the floor of the mouth (the 2 tumors were near each other but separate entities), a third SCC in the right aryepiglottic fold, and a grade 2 follicular lymphoma diagnosed “by coincidence” in the lymph nodes of the neck.

The 3 SCCs in the upper aerodigestive tract were in line with the concept of field cancerization, the clinicians note. Multiple adjacent but independent tumors in the mucosa may arise from exposure to carcinogens, which can induce dysplastic changes that lead to malignancy. Moreover, although synchronous cancer of the head and neck regions and follicular lymphoma are rare, one of the potential risk factors for follicular lymphoma is smoking, the authors say. Their patient had been a smoker for 56 years.

Related: Tracking a Tumor

The authors recommend a “more liberal approach” to examination and a “generous use” of PET-CT for patients with malignancies of the head and neck regions, particularly in patients with obvious risk factors, such as a long history of smoking or alcohol abuse. They add that PET-CT is also a useful tool in assessing tumor dissemination and prognosis of individual carcinomas—an important benefit in planning different treatments.

Source:
Heidemann LN, Johansen J, Larsen SR, Sørensen JA. BMJ Case Rep. 2016;pii: bcr2015214047.
doi: 10.1136/bcr-2015-214047.

Up to 6% of patients with head and neck squamous cell carcinoma (SCC) also have synchronous second primary cancers (SPCs). However, the synchronous cancers may be missed in a usual examination that relies on CT and MRI scans.

Related: Complex Malignancies: A Diagnostic and Therapeutic Trilemma

Clinicians from Odense University Hospital in Denmark report on a patient who presented with only tongue pain as a symptom but was found to have 4 SPCs. The CT and MRI results were inconclusive due to artifacts from metal dental fillings. However, a positron emission tomography (PET)-CT scan “easily revealed” the 3 coinciding malignancies because of their increased metabolic activity, the authors say.

Their patient had 4 primary cancers: 1 SCC on the left side of the tongue, 1 in the fold between the tongue and the floor of the mouth (the 2 tumors were near each other but separate entities), a third SCC in the right aryepiglottic fold, and a grade 2 follicular lymphoma diagnosed “by coincidence” in the lymph nodes of the neck.

The 3 SCCs in the upper aerodigestive tract were in line with the concept of field cancerization, the clinicians note. Multiple adjacent but independent tumors in the mucosa may arise from exposure to carcinogens, which can induce dysplastic changes that lead to malignancy. Moreover, although synchronous cancer of the head and neck regions and follicular lymphoma are rare, one of the potential risk factors for follicular lymphoma is smoking, the authors say. Their patient had been a smoker for 56 years.

Related: Tracking a Tumor

The authors recommend a “more liberal approach” to examination and a “generous use” of PET-CT for patients with malignancies of the head and neck regions, particularly in patients with obvious risk factors, such as a long history of smoking or alcohol abuse. They add that PET-CT is also a useful tool in assessing tumor dissemination and prognosis of individual carcinomas—an important benefit in planning different treatments.

Source:
Heidemann LN, Johansen J, Larsen SR, Sørensen JA. BMJ Case Rep. 2016;pii: bcr2015214047.
doi: 10.1136/bcr-2015-214047.

Up to 6% of patients with head and neck squamous cell carcinoma (SCC) also have synchronous second primary cancers (SPCs). However, the synchronous cancers may be missed in a usual examination that relies on CT and MRI scans.

Related: Complex Malignancies: A Diagnostic and Therapeutic Trilemma

Clinicians from Odense University Hospital in Denmark report on a patient who presented with only tongue pain as a symptom but was found to have 4 SPCs. The CT and MRI results were inconclusive due to artifacts from metal dental fillings. However, a positron emission tomography (PET)-CT scan “easily revealed” the 3 coinciding malignancies because of their increased metabolic activity, the authors say.

Their patient had 4 primary cancers: 1 SCC on the left side of the tongue, 1 in the fold between the tongue and the floor of the mouth (the 2 tumors were near each other but separate entities), a third SCC in the right aryepiglottic fold, and a grade 2 follicular lymphoma diagnosed “by coincidence” in the lymph nodes of the neck.

The 3 SCCs in the upper aerodigestive tract were in line with the concept of field cancerization, the clinicians note. Multiple adjacent but independent tumors in the mucosa may arise from exposure to carcinogens, which can induce dysplastic changes that lead to malignancy. Moreover, although synchronous cancer of the head and neck regions and follicular lymphoma are rare, one of the potential risk factors for follicular lymphoma is smoking, the authors say. Their patient had been a smoker for 56 years.

Related: Tracking a Tumor

The authors recommend a “more liberal approach” to examination and a “generous use” of PET-CT for patients with malignancies of the head and neck regions, particularly in patients with obvious risk factors, such as a long history of smoking or alcohol abuse. They add that PET-CT is also a useful tool in assessing tumor dissemination and prognosis of individual carcinomas—an important benefit in planning different treatments.

Source:
Heidemann LN, Johansen J, Larsen SR, Sørensen JA. BMJ Case Rep. 2016;pii: bcr2015214047.
doi: 10.1136/bcr-2015-214047.

CHICAGO – Combining an immunostimulatory agent with the PD-1 checkpoint inhibitor pembrolizumab appeared quite safe and very tolerable, in a small phase Ib study.

There were some signs of efficacy against a variety of solid tumors, as well as biomarker trends showing immune activity.

In the phase Ib trial, researchers combined escalating doses (0.45-5.0 mg/kg) of PF-2566, an investigative immunostimulatory agent, with the anti–PD-1 checkpoint inhibitor pembrolizumab at 2 mg/kg, with both drugs given intravenously once every 3 weeks for a maximum of 32 cycles. A primary objective of the trial was to determine a maximum tolerated dose. Secondary objectives were to assess safety and tolerability and to determine any antitumor responses.

PF-2566 (Utomilumab/PF-05082566) is a monoclonal agonist targeting 4-1BB, a “costimulatory molecule that’s induced upon T-cell receptor activation and ultimately enhances cytotoxic T-cell response and effector status,” said Dr. Anthony Tolcher of the START Center for Cancer Care, San Antonio, at the annual meeting of the American Society of Clinical Oncology.

Eligible patients were 18 years or older, had a performance status of 0-1, and had advanced or metastatic solid tumors that had progressed on standard therapy or for which no standard therapy was available. They could not have had any form of immunosuppressive therapy in the 2 weeks prior to registration, a monoclonal antibody in the 2 months before the first dose, or any symptomatic or progressing central nervous system primary malignancies. Prior pembrolizumab was permitted.

Twenty-three patients (14 males) were heavily pretreated with a median of three prior therapies (range 0-9) for a variety of cancers, including six non–small-cell lung, five renal cell, three head and neck, and two each pancreatic and thyroid cancers.

Good safety and tolerability profiles

The most prevalent treatment-emergent adverse events (AEs) were fatigue, rash, cough, nausea, and decreased appetite, affecting 7-10 patients each. All were grade 1/2 except for one grade 3/4 case of fatigue and three cases of grade 3/4 anemia among the 23 patients. Most treatment-related AE’s were grade 1/2, largely fatigue (n = 8) and rash (n = 9). There was one case each of grade 3 adrenal insufficiency and hypokalemia. No patient discontinued the trial because of a treatment-related toxicity. Dr. Tolcher noted that adrenal insufficiency has been reported previously with the use of PD-1 inhibitors. “There does not appear to be any evidence of synergistic or additive toxicity in this patient population,” he said.

Neither drug affected the pharmacokinetics of the other drug or the development of antibodies to the other drug. The maximum tolerated dose of PF-2566 was at least 5 mg/kg every 3 weeks when combined with pembrolizumab 2 mg/kg. No dose-limiting toxicity was observed across the PF-2566 dosing range. And there were no treatment-emergent AEs of clinical relevance.

Pharmacodynamics and efficacy

By day 1 of cycle 5, “there [was] a trend toward increasing numbers of activated CD8 [cytotoxic] T cells in patients who ultimately responded or had a complete response, compared to those that had stable disease or progressive disease. The same actually applies to the effector memory T cells,” Dr. Tolcher said but was careful to point out that the sample sizes were small and it was only a trend. Similarly, circulating levels of gamma-interferon, often used as a biomarker of activated T cells, were higher at 6 and 24 hours post dose in cycle 5 for those patients who ultimately had partial or complete responses, compared with those with progressive or stable disease.

Among the 23 patients, there were two confirmed complete responses and four partial responses as well as one unconfirmed partial response. If responses occurred, they often were durable past 1 year and even out close to 2 years.

The strengths of this study were that it enrolled heavily pretreated patients and there were no drug-drug interactions, no dose-limiting toxicities, and no treatment-related AE’s leading to discontinuation, “so in general a very well-tolerated immunotherapy combination,” said discussant Dr. David Spigel of the Sarah Cannon Research Institute in Nashville, Tenn. There were also some durable responses, and he said it was interesting to see that there were some blood biomarkers that correlated with responses.

“It was hard for me to find any weaknesses to this,” Dr. Spigel said, beside the fact that it was a small study. “So what does this change?” He said the combination of pembrolizumab and PF-2566 looks promising in light of some sustained responses in refractory tumors and its safety profile. For the future, expansion trial cohorts are still needed to confirm activity and safety, especially hepatic safety based on trial results with similar drugs, and PF-2566 is already being tested with rituximab in lymphoma and with an anti-CCR4 compound (mogamulizumab).

The study was sponsored by Pfizer and Merck. Dr. Tolcher has ties to several companies, including Pfizer and Merck. Dr. Spigel has ties to several companies, including Pfizer.

CHICAGO – Combining an immunostimulatory agent with the PD-1 checkpoint inhibitor pembrolizumab appeared quite safe and very tolerable, in a small phase Ib study.

There were some signs of efficacy against a variety of solid tumors, as well as biomarker trends showing immune activity.

In the phase Ib trial, researchers combined escalating doses (0.45-5.0 mg/kg) of PF-2566, an investigative immunostimulatory agent, with the anti–PD-1 checkpoint inhibitor pembrolizumab at 2 mg/kg, with both drugs given intravenously once every 3 weeks for a maximum of 32 cycles. A primary objective of the trial was to determine a maximum tolerated dose. Secondary objectives were to assess safety and tolerability and to determine any antitumor responses.

PF-2566 (Utomilumab/PF-05082566) is a monoclonal agonist targeting 4-1BB, a “costimulatory molecule that’s induced upon T-cell receptor activation and ultimately enhances cytotoxic T-cell response and effector status,” said Dr. Anthony Tolcher of the START Center for Cancer Care, San Antonio, at the annual meeting of the American Society of Clinical Oncology.

Eligible patients were 18 years or older, had a performance status of 0-1, and had advanced or metastatic solid tumors that had progressed on standard therapy or for which no standard therapy was available. They could not have had any form of immunosuppressive therapy in the 2 weeks prior to registration, a monoclonal antibody in the 2 months before the first dose, or any symptomatic or progressing central nervous system primary malignancies. Prior pembrolizumab was permitted.

Twenty-three patients (14 males) were heavily pretreated with a median of three prior therapies (range 0-9) for a variety of cancers, including six non–small-cell lung, five renal cell, three head and neck, and two each pancreatic and thyroid cancers.

Good safety and tolerability profiles

The most prevalent treatment-emergent adverse events (AEs) were fatigue, rash, cough, nausea, and decreased appetite, affecting 7-10 patients each. All were grade 1/2 except for one grade 3/4 case of fatigue and three cases of grade 3/4 anemia among the 23 patients. Most treatment-related AE’s were grade 1/2, largely fatigue (n = 8) and rash (n = 9). There was one case each of grade 3 adrenal insufficiency and hypokalemia. No patient discontinued the trial because of a treatment-related toxicity. Dr. Tolcher noted that adrenal insufficiency has been reported previously with the use of PD-1 inhibitors. “There does not appear to be any evidence of synergistic or additive toxicity in this patient population,” he said.

Neither drug affected the pharmacokinetics of the other drug or the development of antibodies to the other drug. The maximum tolerated dose of PF-2566 was at least 5 mg/kg every 3 weeks when combined with pembrolizumab 2 mg/kg. No dose-limiting toxicity was observed across the PF-2566 dosing range. And there were no treatment-emergent AEs of clinical relevance.

Pharmacodynamics and efficacy

By day 1 of cycle 5, “there [was] a trend toward increasing numbers of activated CD8 [cytotoxic] T cells in patients who ultimately responded or had a complete response, compared to those that had stable disease or progressive disease. The same actually applies to the effector memory T cells,” Dr. Tolcher said but was careful to point out that the sample sizes were small and it was only a trend. Similarly, circulating levels of gamma-interferon, often used as a biomarker of activated T cells, were higher at 6 and 24 hours post dose in cycle 5 for those patients who ultimately had partial or complete responses, compared with those with progressive or stable disease.

Among the 23 patients, there were two confirmed complete responses and four partial responses as well as one unconfirmed partial response. If responses occurred, they often were durable past 1 year and even out close to 2 years.

The strengths of this study were that it enrolled heavily pretreated patients and there were no drug-drug interactions, no dose-limiting toxicities, and no treatment-related AE’s leading to discontinuation, “so in general a very well-tolerated immunotherapy combination,” said discussant Dr. David Spigel of the Sarah Cannon Research Institute in Nashville, Tenn. There were also some durable responses, and he said it was interesting to see that there were some blood biomarkers that correlated with responses.

“It was hard for me to find any weaknesses to this,” Dr. Spigel said, beside the fact that it was a small study. “So what does this change?” He said the combination of pembrolizumab and PF-2566 looks promising in light of some sustained responses in refractory tumors and its safety profile. For the future, expansion trial cohorts are still needed to confirm activity and safety, especially hepatic safety based on trial results with similar drugs, and PF-2566 is already being tested with rituximab in lymphoma and with an anti-CCR4 compound (mogamulizumab).

The study was sponsored by Pfizer and Merck. Dr. Tolcher has ties to several companies, including Pfizer and Merck. Dr. Spigel has ties to several companies, including Pfizer.

CHICAGO – Combining an immunostimulatory agent with the PD-1 checkpoint inhibitor pembrolizumab appeared quite safe and very tolerable, in a small phase Ib study.

There were some signs of efficacy against a variety of solid tumors, as well as biomarker trends showing immune activity.

In the phase Ib trial, researchers combined escalating doses (0.45-5.0 mg/kg) of PF-2566, an investigative immunostimulatory agent, with the anti–PD-1 checkpoint inhibitor pembrolizumab at 2 mg/kg, with both drugs given intravenously once every 3 weeks for a maximum of 32 cycles. A primary objective of the trial was to determine a maximum tolerated dose. Secondary objectives were to assess safety and tolerability and to determine any antitumor responses.

PF-2566 (Utomilumab/PF-05082566) is a monoclonal agonist targeting 4-1BB, a “costimulatory molecule that’s induced upon T-cell receptor activation and ultimately enhances cytotoxic T-cell response and effector status,” said Dr. Anthony Tolcher of the START Center for Cancer Care, San Antonio, at the annual meeting of the American Society of Clinical Oncology.

Eligible patients were 18 years or older, had a performance status of 0-1, and had advanced or metastatic solid tumors that had progressed on standard therapy or for which no standard therapy was available. They could not have had any form of immunosuppressive therapy in the 2 weeks prior to registration, a monoclonal antibody in the 2 months before the first dose, or any symptomatic or progressing central nervous system primary malignancies. Prior pembrolizumab was permitted.

Twenty-three patients (14 males) were heavily pretreated with a median of three prior therapies (range 0-9) for a variety of cancers, including six non–small-cell lung, five renal cell, three head and neck, and two each pancreatic and thyroid cancers.

Good safety and tolerability profiles

The most prevalent treatment-emergent adverse events (AEs) were fatigue, rash, cough, nausea, and decreased appetite, affecting 7-10 patients each. All were grade 1/2 except for one grade 3/4 case of fatigue and three cases of grade 3/4 anemia among the 23 patients. Most treatment-related AE’s were grade 1/2, largely fatigue (n = 8) and rash (n = 9). There was one case each of grade 3 adrenal insufficiency and hypokalemia. No patient discontinued the trial because of a treatment-related toxicity. Dr. Tolcher noted that adrenal insufficiency has been reported previously with the use of PD-1 inhibitors. “There does not appear to be any evidence of synergistic or additive toxicity in this patient population,” he said.

Neither drug affected the pharmacokinetics of the other drug or the development of antibodies to the other drug. The maximum tolerated dose of PF-2566 was at least 5 mg/kg every 3 weeks when combined with pembrolizumab 2 mg/kg. No dose-limiting toxicity was observed across the PF-2566 dosing range. And there were no treatment-emergent AEs of clinical relevance.

Pharmacodynamics and efficacy

By day 1 of cycle 5, “there [was] a trend toward increasing numbers of activated CD8 [cytotoxic] T cells in patients who ultimately responded or had a complete response, compared to those that had stable disease or progressive disease. The same actually applies to the effector memory T cells,” Dr. Tolcher said but was careful to point out that the sample sizes were small and it was only a trend. Similarly, circulating levels of gamma-interferon, often used as a biomarker of activated T cells, were higher at 6 and 24 hours post dose in cycle 5 for those patients who ultimately had partial or complete responses, compared with those with progressive or stable disease.

Among the 23 patients, there were two confirmed complete responses and four partial responses as well as one unconfirmed partial response. If responses occurred, they often were durable past 1 year and even out close to 2 years.

The strengths of this study were that it enrolled heavily pretreated patients and there were no drug-drug interactions, no dose-limiting toxicities, and no treatment-related AE’s leading to discontinuation, “so in general a very well-tolerated immunotherapy combination,” said discussant Dr. David Spigel of the Sarah Cannon Research Institute in Nashville, Tenn. There were also some durable responses, and he said it was interesting to see that there were some blood biomarkers that correlated with responses.

“It was hard for me to find any weaknesses to this,” Dr. Spigel said, beside the fact that it was a small study. “So what does this change?” He said the combination of pembrolizumab and PF-2566 looks promising in light of some sustained responses in refractory tumors and its safety profile. For the future, expansion trial cohorts are still needed to confirm activity and safety, especially hepatic safety based on trial results with similar drugs, and PF-2566 is already being tested with rituximab in lymphoma and with an anti-CCR4 compound (mogamulizumab).

The study was sponsored by Pfizer and Merck. Dr. Tolcher has ties to several companies, including Pfizer and Merck. Dr. Spigel has ties to several companies, including Pfizer.

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

[email protected]

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.