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Preop G-tubes save money in head and neck cancer resections
SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.
The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.
Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.
“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.
That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).
Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.
Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m2 and 26 kg/m2 in the postop group (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.
There was no outside funding for the work, and Dr. Waltonen had no disclosures.
SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.
The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.
Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.
“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.
That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).
Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.
Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m2 and 26 kg/m2 in the postop group (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.
There was no outside funding for the work, and Dr. Waltonen had no disclosures.
SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.
The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.
Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.
“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.
That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).
Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.
Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m2 and 26 kg/m2 in the postop group (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.
There was no outside funding for the work, and Dr. Waltonen had no disclosures.
AT AHNS 2016
Key clinical point: It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after.
Major finding: At 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postop group, a savings of $9,248 per patient.
Data source: Review of 184 patients.
Disclosures: There was no outside funding for the work, and the presenter had no disclosures.
Intraoperative nerve stimulation reduces risk of shoulder pain from neck dissection
SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.
Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.
After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.
At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.
The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.
Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.
The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.
There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.
SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.
Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.
After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.
At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.
The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.
Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.
The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.
There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.
SEATTLE – Direct, intraoperative electrical stimulation of the spinal accessory nerve reduced shoulder pain and dysfunction from oncologic neck dissection in a small, randomized trial.
Shoulder problems are common after neck dissection because of traction and compression of the spinal accessory nerve. Although brief electrical stimulation (BES) has been shown before to improve regeneration and recovery of injured peripheral nerves, it hasn’t been shown until now to help patients recover from neck surgery, said investigator Brittany Barber, MD, a fifth-year resident at the University of Alberta, Edmonton.
After neck dissection in 21 patients, the investigators wrapped a small electrode (Automatic Periodic Stimulation [APS] electrode, Medtronic) around the spinal accessory nerve at the base of the skull on the side of the neck with the most extensive nodal burden; the electrode delivered 100-msec pulses at 20 Hz and 3-5 V for an hour, and then the neck was closed. The team compared outcomes with 20 controls who had neck dissections without BES.
At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Outcome Score, while the controls lost a mean of 29.4 points. The Murley score measures shoulder pain, performance of daily tasks, range of motion, and strength; higher scores are better. Similarly, BES patients lost a mean of 16.2 points on the 50-point Neck Dissection Impairment Index, while controls lost 30.1 points, and controls performed markedly worse on nerve conduction studies. In short, BES patients “were less likely to have clinically significant shoulder dysfunction” after surgery, Dr. Barber said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.
The APS electrode is a tiny silicone cuff with a metal conductor. The device was originally designed to monitor recurrent laryngeal nerve function during thyroid surgery. “We had [Medtronic] write a software patch” so it could be used for stimulation, she said.
The team is planning a larger, multicenter trial to shore up their findings, and also plans to test the device for hypoglossal nerve preservation after resection.
Transcutaneous nerve stimulation is another option, but it’s a bit uncomfortable and patients often don’t complete their sessions. “Compliance is not as good as with a single intraoperative procedure,” and the results aren’t that great. “We thought this might be a better alternative,” Dr. Barber said.
The two groups were well matched: Mean age was about 60 years and most patients had advanced-stage tumors. There was no difference in preop shoulder problems or risks for poor postop shoulder outcomes, and no difference in the number of level 5 neck dissections or mean number of lymph nodes removed during surgery.
There was no outside funding for the work. Dr. Barber had no disclosures; a coinvestigator was a Medtronic consultant.
AT AHNS 2016
Key clinical point: Direct, intraoperative electrical stimulation of the spinal accessory nerve reduces shoulder pain and dysfunction from oncologic neck dissection.
Major finding: At 12 months, the BES group had an 8.4 point drop from baseline on the 100-point Constant Murley Shoulder Score, while the controls lost a mean of 29.4 points.
Data source: Randomized trial with 41 patients.
Disclosures: There was no outside funding for the work. The presenter had no disclosures; a co-investigator was a Medtronic consultant.
FDA grants accelerated approval to pembrolizumab for advanced HNSCC
The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.
The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.
The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.
Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.
The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.
On Twitter @NikolaidesLaura
The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.
The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.
The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.
Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.
The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.
On Twitter @NikolaidesLaura
The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.
The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.
The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.
Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.
The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.
On Twitter @NikolaidesLaura
Skip SNL biopsy for desmoplastic melanoma
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.
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.
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.
AT AHNS 2016
Key clinical point: 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.
Major finding: 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%).
Data source: Retrospective case-control study with 92 patients
Disclosures: There was no outside funding for the work, and the presenter had no disclosures.
Testosterone might counteract chemotherapy heart damage
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.
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Dr. Benjamin Judson |
The data are promising but preliminary for a problem we see a lot, chemotherapy-induced cardiotoxicity that presents years after treatment. We have to be really careful before we give testosterone to anyone who is under active treatment for cancer, because I don’t think we really know if it’s safe.
Benjamin Judson, MD, is an associate professor of otolaryngologic surgery at Yale Medical School in New Haven, Conn. He moderated Dr. Chamberlain’s talk and was not involved in the study.
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Dr. Benjamin Judson |
The data are promising but preliminary for a problem we see a lot, chemotherapy-induced cardiotoxicity that presents years after treatment. We have to be really careful before we give testosterone to anyone who is under active treatment for cancer, because I don’t think we really know if it’s safe.
Benjamin Judson, MD, is an associate professor of otolaryngologic surgery at Yale Medical School in New Haven, Conn. He moderated Dr. Chamberlain’s talk and was not involved in the study.
|
|
Dr. Benjamin Judson |
The data are promising but preliminary for a problem we see a lot, chemotherapy-induced cardiotoxicity that presents years after treatment. We have to be really careful before we give testosterone to anyone who is under active treatment for cancer, because I don’t think we really know if it’s safe.
Benjamin Judson, MD, is an associate professor of otolaryngologic surgery at Yale Medical School in New Haven, Conn. He moderated Dr. Chamberlain’s talk and was not involved in the study.
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.
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.
AT AHNS 2016
Key clinical point: Adjunct testosterone improved cardiac function in head, neck, and cervical cancer patients undergoing standard treatment in a small randomized trial.
Major finding: 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), but there was no years-long follow-up to show lasting cardiac benefit.
Data source: Randomized trial with 16 patients.
Disclosures: The National Cancer Institute funded the work. The lead investigator had no disclosures.
FDA grants priority review to nivolumab for head and neck cancer
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.
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.
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.
On Twitter @jessnicolecraig
SU2C announces researcher-industry collaboration on immunotherapy
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.
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.
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.
On Twitter @NikolaidesLaura
Finding Synchronous Cancers
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.
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.
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.
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.
Pembrolizumab paired with immunostimulator is safe and tolerable
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.
AT THE 2016 ASCO ANNUAL MEETING
Key clinical point: Combining an immunostimulator with pembrolizumab had good tolerability and safety.
Major finding: Two complete and four partial responses occurred among 23 patients.
Data source: Phase Ib trial of 23 patients with a variety of solid tumors.
Disclosures: 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.
MyPathway: Targeted therapies show promise in nonindicated tumors
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.
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.
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.
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.
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.
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.
AT THE 2016 ASCO ANNUAL MEETING
Key clinical point: 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.
Major finding: Twenty-nine patients had a major response, and an additional 40 remained stable on treatment.
Data source: The ongoing open-label, phase IIa MyPathway study, including results from the first 129 patients.
Disclosures: 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.
