Roxanne Nelson

Early data show that treatment with the immune checkpoint inhibitor nivolumab (Opdivo) resulted in a 5-year overall survival rate of 16% among patients with advanced non–small-cell lung cancer (NSCLC).

In comparison, the 5-year survival rate for patients with advanced lung and bronchus cancer, according to SEER data, is 4.3%, and for those with advanced NSCLC, 4.9%.

“This is the first report of the long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor,” said Julie Brahmer, MD, of the Bloomberg Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore.

For a small subset of patients, immunotherapy can work for a very long time, explained Dr. Brahmer, who discussed her findings during a presscast at the annual meeting of the American Association for Cancer Research.

The 5-year overall survival rate that was reported in this study was much higher than what has been seen for this patient population who receive the standard of care. Statistics show that the majority of patients with advanced disease will die within a year of their diagnosis, Dr. Brahmer pointed out.

The findings presented at the meeting are updated results from the phase Ib CA209-003 dose-escalation cohort expansion trial that comprised 129 patients with heavily pretreated, advanced NSCLC . The cohort was randomized to receive nivolumab once every 2 weeks for up to 2 years at one of three dose levels: 1 mg/kg, 3 mg/kg, or 10 mg/kg.

A previous analysis of the data showed promising activity, and findings from subsequent clinical trials led to the approval of nivolumab for use in the second line setting of advanced NSCLC.

Dr. Brahmer now reported findings based on 5-year results of this phase Ib trial. “This analysis is based on a minimum follow up of 58 months,” she said.

The overall 5-year survival rates for squamous NSCLC were 16%, and the rates for nonsquamous were 15%.

At 1 year, overall survival was 42%. At 2 years, it was 24%, and at 3 years, 18%.

“After 3 years, the survival curve has plateaued out, which is similar to what has been seen in the past in other diseases treated with immunotherapy,” Dr. Brahmer noted.

Within the cohort, there were 16 patients who had survived for at least 5 years. Of this group, 12 achieved a partial response, 2 patients had stable disease, and 2 had progressive disease.

Dr. Brahmer pointed out that there was nothing different or unusual among the 16 patients who survived for 5 years, compared with the rest of the cohort. Their characteristics were similar to others in the study, most of them were former smokers, and they had very similar rates of different histologies.

One interesting note was that within that group, there were two patients with EGFR mutations. “We usually don’t expect them to do well with immunotherapy,” she said.

Dr. Brahmer received research funding from, and is an adviser to, Bristol-Myers Squibb, which funded the study.

[email protected]

Early data show that treatment with the immune checkpoint inhibitor nivolumab (Opdivo) resulted in a 5-year overall survival rate of 16% among patients with advanced non–small-cell lung cancer (NSCLC).

In comparison, the 5-year survival rate for patients with advanced lung and bronchus cancer, according to SEER data, is 4.3%, and for those with advanced NSCLC, 4.9%.

“This is the first report of the long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor,” said Julie Brahmer, MD, of the Bloomberg Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore.

For a small subset of patients, immunotherapy can work for a very long time, explained Dr. Brahmer, who discussed her findings during a presscast at the annual meeting of the American Association for Cancer Research.

The 5-year overall survival rate that was reported in this study was much higher than what has been seen for this patient population who receive the standard of care. Statistics show that the majority of patients with advanced disease will die within a year of their diagnosis, Dr. Brahmer pointed out.

The findings presented at the meeting are updated results from the phase Ib CA209-003 dose-escalation cohort expansion trial that comprised 129 patients with heavily pretreated, advanced NSCLC . The cohort was randomized to receive nivolumab once every 2 weeks for up to 2 years at one of three dose levels: 1 mg/kg, 3 mg/kg, or 10 mg/kg.

A previous analysis of the data showed promising activity, and findings from subsequent clinical trials led to the approval of nivolumab for use in the second line setting of advanced NSCLC.

Dr. Brahmer now reported findings based on 5-year results of this phase Ib trial. “This analysis is based on a minimum follow up of 58 months,” she said.

The overall 5-year survival rates for squamous NSCLC were 16%, and the rates for nonsquamous were 15%.

At 1 year, overall survival was 42%. At 2 years, it was 24%, and at 3 years, 18%.

“After 3 years, the survival curve has plateaued out, which is similar to what has been seen in the past in other diseases treated with immunotherapy,” Dr. Brahmer noted.

Within the cohort, there were 16 patients who had survived for at least 5 years. Of this group, 12 achieved a partial response, 2 patients had stable disease, and 2 had progressive disease.

Dr. Brahmer pointed out that there was nothing different or unusual among the 16 patients who survived for 5 years, compared with the rest of the cohort. Their characteristics were similar to others in the study, most of them were former smokers, and they had very similar rates of different histologies.

One interesting note was that within that group, there were two patients with EGFR mutations. “We usually don’t expect them to do well with immunotherapy,” she said.

Dr. Brahmer received research funding from, and is an adviser to, Bristol-Myers Squibb, which funded the study.

[email protected]

Early data show that treatment with the immune checkpoint inhibitor nivolumab (Opdivo) resulted in a 5-year overall survival rate of 16% among patients with advanced non–small-cell lung cancer (NSCLC).

In comparison, the 5-year survival rate for patients with advanced lung and bronchus cancer, according to SEER data, is 4.3%, and for those with advanced NSCLC, 4.9%.

“This is the first report of the long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor,” said Julie Brahmer, MD, of the Bloomberg Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore.

For a small subset of patients, immunotherapy can work for a very long time, explained Dr. Brahmer, who discussed her findings during a presscast at the annual meeting of the American Association for Cancer Research.

The 5-year overall survival rate that was reported in this study was much higher than what has been seen for this patient population who receive the standard of care. Statistics show that the majority of patients with advanced disease will die within a year of their diagnosis, Dr. Brahmer pointed out.

The findings presented at the meeting are updated results from the phase Ib CA209-003 dose-escalation cohort expansion trial that comprised 129 patients with heavily pretreated, advanced NSCLC . The cohort was randomized to receive nivolumab once every 2 weeks for up to 2 years at one of three dose levels: 1 mg/kg, 3 mg/kg, or 10 mg/kg.

A previous analysis of the data showed promising activity, and findings from subsequent clinical trials led to the approval of nivolumab for use in the second line setting of advanced NSCLC.

Dr. Brahmer now reported findings based on 5-year results of this phase Ib trial. “This analysis is based on a minimum follow up of 58 months,” she said.

The overall 5-year survival rates for squamous NSCLC were 16%, and the rates for nonsquamous were 15%.

At 1 year, overall survival was 42%. At 2 years, it was 24%, and at 3 years, 18%.

“After 3 years, the survival curve has plateaued out, which is similar to what has been seen in the past in other diseases treated with immunotherapy,” Dr. Brahmer noted.

Within the cohort, there were 16 patients who had survived for at least 5 years. Of this group, 12 achieved a partial response, 2 patients had stable disease, and 2 had progressive disease.

Dr. Brahmer pointed out that there was nothing different or unusual among the 16 patients who survived for 5 years, compared with the rest of the cohort. Their characteristics were similar to others in the study, most of them were former smokers, and they had very similar rates of different histologies.

One interesting note was that within that group, there were two patients with EGFR mutations. “We usually don’t expect them to do well with immunotherapy,” she said.

Dr. Brahmer received research funding from, and is an adviser to, Bristol-Myers Squibb, which funded the study.

[email protected]

The combination of trastuzumab (Herceptin) and lapatinib (Tykerb) resulted in an overall objective response rate of 30% in heavily pretreated patients with HER2-positive metastatic colorectal cancer, according to findings presented at the annual meeting of the American Association for Cancer Research.

Of 33 patients, 2 patients achieved complete responses and 8 had partial responses, while 13 patients achieved stable disease. This brought the total clinical benefit rate to 70% at the time of data cutoff on Feb. 28.

“There is a large unmet need in colorectal cancer,” said study author, Silvia Marsoni, MD, director of the precision medicine unit at the Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia–IRCCS in Turin, Italy.

“The combination of drugs really had a great impact on the tumor,” said Dr. Marsoni, who discussed the findings at a presscast. “One of these complete responders is still alive without evidence of disease at almost 36 months from the beginning of his treatment. This was a very good duration of response.”

HER2 amplification is found in 5% of RAS wild-type metastatic colorectal cancer cases. Dual HER2 blockade with both trastuzumab and lapatinib had inhibited tumor growth in preliminary studies, but that has not been the case for either drug used alone.

The HERACLES trial was conducted at four centers in Italy and enrolled 33 patients with RAS wild-type, HER2-positive tumors that were refractory to standard of care treatments, including the epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab.

“These patients were heavily pretreated and 75% had four or more prior treatments,” explained Dr. Marsoni.

All participants received trastuzumab intravenously with a 4 mg/kg loading dose followed by 2 mg/kg weekly, and lapatinib was given orally at 1,000 mg daily. Treatment continued until disease progression.

The primary endpoint was the objective response rate, and secondary endpoints included progression-free survival and safety.

The two patients who achieved a complete response continue to be disease free, and both had tumors that were refractory to cetuximab and resistant to all standard treatment.

Historically, the response rate in metastatic colorectal cancer after second-line treatment is very low, at less than 5% with chemotherapy and about 10%-20% with anti-EGFR therapy.

“There was really no toxicity,” explained Dr. Marsoni. “We used a lapatinib dose that was about 20% less than what is used in breast cancer to avoid GI toxicity.”

Only six patients (18%) experienced grade 3 side effects, which included fatigue, skin rash, and elevated bilirubin.

“In conclusion, we can say that, even if HER2-positive patients in colon cancer are only 3% of the population, they are still a little and important piece of the cake that can be actively targeted with a new chemotherapy-free regimen,” said Dr. Marsoni. “We have a new potential treatment for this population.”

The combination of trastuzumab (Herceptin) and lapatinib (Tykerb) resulted in an overall objective response rate of 30% in heavily pretreated patients with HER2-positive metastatic colorectal cancer, according to findings presented at the annual meeting of the American Association for Cancer Research.

Of 33 patients, 2 patients achieved complete responses and 8 had partial responses, while 13 patients achieved stable disease. This brought the total clinical benefit rate to 70% at the time of data cutoff on Feb. 28.

“There is a large unmet need in colorectal cancer,” said study author, Silvia Marsoni, MD, director of the precision medicine unit at the Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia–IRCCS in Turin, Italy.

“The combination of drugs really had a great impact on the tumor,” said Dr. Marsoni, who discussed the findings at a presscast. “One of these complete responders is still alive without evidence of disease at almost 36 months from the beginning of his treatment. This was a very good duration of response.”

HER2 amplification is found in 5% of RAS wild-type metastatic colorectal cancer cases. Dual HER2 blockade with both trastuzumab and lapatinib had inhibited tumor growth in preliminary studies, but that has not been the case for either drug used alone.

The HERACLES trial was conducted at four centers in Italy and enrolled 33 patients with RAS wild-type, HER2-positive tumors that were refractory to standard of care treatments, including the epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab.

“These patients were heavily pretreated and 75% had four or more prior treatments,” explained Dr. Marsoni.

All participants received trastuzumab intravenously with a 4 mg/kg loading dose followed by 2 mg/kg weekly, and lapatinib was given orally at 1,000 mg daily. Treatment continued until disease progression.

The primary endpoint was the objective response rate, and secondary endpoints included progression-free survival and safety.

The two patients who achieved a complete response continue to be disease free, and both had tumors that were refractory to cetuximab and resistant to all standard treatment.

Historically, the response rate in metastatic colorectal cancer after second-line treatment is very low, at less than 5% with chemotherapy and about 10%-20% with anti-EGFR therapy.

“There was really no toxicity,” explained Dr. Marsoni. “We used a lapatinib dose that was about 20% less than what is used in breast cancer to avoid GI toxicity.”

Only six patients (18%) experienced grade 3 side effects, which included fatigue, skin rash, and elevated bilirubin.

“In conclusion, we can say that, even if HER2-positive patients in colon cancer are only 3% of the population, they are still a little and important piece of the cake that can be actively targeted with a new chemotherapy-free regimen,” said Dr. Marsoni. “We have a new potential treatment for this population.”

The combination of trastuzumab (Herceptin) and lapatinib (Tykerb) resulted in an overall objective response rate of 30% in heavily pretreated patients with HER2-positive metastatic colorectal cancer, according to findings presented at the annual meeting of the American Association for Cancer Research.

Of 33 patients, 2 patients achieved complete responses and 8 had partial responses, while 13 patients achieved stable disease. This brought the total clinical benefit rate to 70% at the time of data cutoff on Feb. 28.

“There is a large unmet need in colorectal cancer,” said study author, Silvia Marsoni, MD, director of the precision medicine unit at the Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia–IRCCS in Turin, Italy.

“The combination of drugs really had a great impact on the tumor,” said Dr. Marsoni, who discussed the findings at a presscast. “One of these complete responders is still alive without evidence of disease at almost 36 months from the beginning of his treatment. This was a very good duration of response.”

HER2 amplification is found in 5% of RAS wild-type metastatic colorectal cancer cases. Dual HER2 blockade with both trastuzumab and lapatinib had inhibited tumor growth in preliminary studies, but that has not been the case for either drug used alone.

The HERACLES trial was conducted at four centers in Italy and enrolled 33 patients with RAS wild-type, HER2-positive tumors that were refractory to standard of care treatments, including the epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab.

“These patients were heavily pretreated and 75% had four or more prior treatments,” explained Dr. Marsoni.

All participants received trastuzumab intravenously with a 4 mg/kg loading dose followed by 2 mg/kg weekly, and lapatinib was given orally at 1,000 mg daily. Treatment continued until disease progression.

The primary endpoint was the objective response rate, and secondary endpoints included progression-free survival and safety.

The two patients who achieved a complete response continue to be disease free, and both had tumors that were refractory to cetuximab and resistant to all standard treatment.

Historically, the response rate in metastatic colorectal cancer after second-line treatment is very low, at less than 5% with chemotherapy and about 10%-20% with anti-EGFR therapy.

“There was really no toxicity,” explained Dr. Marsoni. “We used a lapatinib dose that was about 20% less than what is used in breast cancer to avoid GI toxicity.”

Only six patients (18%) experienced grade 3 side effects, which included fatigue, skin rash, and elevated bilirubin.

“In conclusion, we can say that, even if HER2-positive patients in colon cancer are only 3% of the population, they are still a little and important piece of the cake that can be actively targeted with a new chemotherapy-free regimen,” said Dr. Marsoni. “We have a new potential treatment for this population.”

SEATTLE – Sentinel lymph node biopsy is widely used in patients with early-stage breast cancer for staging the axilla, but it can be safely omitted in some patients, according to new research presented at the annual Society of Surgical Oncology Cancer Symposium.

In women aged 70 years and older with hormone receptor (HR)–positive invasive breast cancer, the risk of nodal involvement is 14%-15%, which adds support to the premise that sentinel lymph node surgery could be avoided in many of the women deemed to be low risk.

The Choosing Wisely campaign was initiated to reduce excess cost and expenditures in health care. The Society of Surgical Oncology recently released five Choosing Wisely guidelines that included specific tests or procedures commonly ordered but not always necessary in surgical oncology, explained study author Jessemae Welsh, MD, of the Mayo Clinic, Rochester, Minn. One of the recommendations was to avoid routine sentinel node biopsy in clinically node-negative women over age 70 years with hormone receptor–positive invasive breast cancer.

“Their rationale is that hormone therapy is the standard of care in these women and sentinel node surgery has shown no impact on local regional recurrence or breast cancer mortality,” said Dr. Welsh. “Therefore it would be safe to treat this population without any axillary node staging.”

She noted that the average 70-year-old woman may live another 14-16 years. “So the question is, how should we be applying the Choosing Wisely guidelines?”

Dr. Welsh and her colleagues evaluated the factors that might be impacting nodal positivity in this population, and in particular, they looked at T stage and tumor grade.

They used two large databases to identify all women over the age of 70 years with HR+ cN0 invasive disease in the institutional breast surgery database (IBSD, 2008-2016) from the Mayo Clinic and the National Cancer Database (NCDB, 2004-2013).

The rates of patients who were node positive (pN+) were based on those who had undergone axillary surgery.

The researchers then stratified patients by clinical T stage and tumor grade to compare risk of pN+ across strata.

Of 705 selected patients in the IBSD, 191 or 14.3% were pN+ and a similar rate was observed in the NCDB; 15.2% (19,607/129,216). Tumor grade and clinical T stage were associated with pN+.

“The overall rates were about 14% for both databases, and when we stratified this by T stage, we could see increasing node positivity with increasing T stage,” said Dr. Welsh.

In similar fashion, the researchers observed comparable increases when they stratified it by grade. “Increasing grades were associated with increasing rates, especially for grade 2 and higher,” said Dr. Welsh.

When the two factors were combined, the researchers were able to define low-risk criteria as clinical T1a-b, grade 1-2 or clinical T1c, grade 1. The low-risk group accounted for 54.3% (IBSD) and 43.2% (NCDB) of patients, and pN+ rates within this group were 7.6% (IBSD) and 7.4% (NCDB).

Patients outside of this subcohort had pN+ rates of 22.4% (IBSD) and 23.0% (NCDB), which extrapolated to a relative risk of 2.95 (95% CI: 1.97-4.42) and 3.11 (95% CI: 2.99-3.23), respectively (each P less than .001).

“Women in the high-risk group had three times the risk of node positivity as the low-risk group,” she said. “Based on our data, we can say that for grade 1 T1a-c we can omit sentinel node surgery, and also for grade 2 T1 a-b.”

But for grade 3, T2 or higher, or any grade 2 Tc tumors, clinicians should continue to consider sentinel node surgery, taking into account individual patient factors.

The investigator had no disclosures.

SEATTLE – Sentinel lymph node biopsy is widely used in patients with early-stage breast cancer for staging the axilla, but it can be safely omitted in some patients, according to new research presented at the annual Society of Surgical Oncology Cancer Symposium.

In women aged 70 years and older with hormone receptor (HR)–positive invasive breast cancer, the risk of nodal involvement is 14%-15%, which adds support to the premise that sentinel lymph node surgery could be avoided in many of the women deemed to be low risk.

The Choosing Wisely campaign was initiated to reduce excess cost and expenditures in health care. The Society of Surgical Oncology recently released five Choosing Wisely guidelines that included specific tests or procedures commonly ordered but not always necessary in surgical oncology, explained study author Jessemae Welsh, MD, of the Mayo Clinic, Rochester, Minn. One of the recommendations was to avoid routine sentinel node biopsy in clinically node-negative women over age 70 years with hormone receptor–positive invasive breast cancer.

“Their rationale is that hormone therapy is the standard of care in these women and sentinel node surgery has shown no impact on local regional recurrence or breast cancer mortality,” said Dr. Welsh. “Therefore it would be safe to treat this population without any axillary node staging.”

She noted that the average 70-year-old woman may live another 14-16 years. “So the question is, how should we be applying the Choosing Wisely guidelines?”

Dr. Welsh and her colleagues evaluated the factors that might be impacting nodal positivity in this population, and in particular, they looked at T stage and tumor grade.

They used two large databases to identify all women over the age of 70 years with HR+ cN0 invasive disease in the institutional breast surgery database (IBSD, 2008-2016) from the Mayo Clinic and the National Cancer Database (NCDB, 2004-2013).

The rates of patients who were node positive (pN+) were based on those who had undergone axillary surgery.

The researchers then stratified patients by clinical T stage and tumor grade to compare risk of pN+ across strata.

Of 705 selected patients in the IBSD, 191 or 14.3% were pN+ and a similar rate was observed in the NCDB; 15.2% (19,607/129,216). Tumor grade and clinical T stage were associated with pN+.

“The overall rates were about 14% for both databases, and when we stratified this by T stage, we could see increasing node positivity with increasing T stage,” said Dr. Welsh.

In similar fashion, the researchers observed comparable increases when they stratified it by grade. “Increasing grades were associated with increasing rates, especially for grade 2 and higher,” said Dr. Welsh.

When the two factors were combined, the researchers were able to define low-risk criteria as clinical T1a-b, grade 1-2 or clinical T1c, grade 1. The low-risk group accounted for 54.3% (IBSD) and 43.2% (NCDB) of patients, and pN+ rates within this group were 7.6% (IBSD) and 7.4% (NCDB).

Patients outside of this subcohort had pN+ rates of 22.4% (IBSD) and 23.0% (NCDB), which extrapolated to a relative risk of 2.95 (95% CI: 1.97-4.42) and 3.11 (95% CI: 2.99-3.23), respectively (each P less than .001).

“Women in the high-risk group had three times the risk of node positivity as the low-risk group,” she said. “Based on our data, we can say that for grade 1 T1a-c we can omit sentinel node surgery, and also for grade 2 T1 a-b.”

But for grade 3, T2 or higher, or any grade 2 Tc tumors, clinicians should continue to consider sentinel node surgery, taking into account individual patient factors.

The investigator had no disclosures.

SEATTLE – Sentinel lymph node biopsy is widely used in patients with early-stage breast cancer for staging the axilla, but it can be safely omitted in some patients, according to new research presented at the annual Society of Surgical Oncology Cancer Symposium.

In women aged 70 years and older with hormone receptor (HR)–positive invasive breast cancer, the risk of nodal involvement is 14%-15%, which adds support to the premise that sentinel lymph node surgery could be avoided in many of the women deemed to be low risk.

The Choosing Wisely campaign was initiated to reduce excess cost and expenditures in health care. The Society of Surgical Oncology recently released five Choosing Wisely guidelines that included specific tests or procedures commonly ordered but not always necessary in surgical oncology, explained study author Jessemae Welsh, MD, of the Mayo Clinic, Rochester, Minn. One of the recommendations was to avoid routine sentinel node biopsy in clinically node-negative women over age 70 years with hormone receptor–positive invasive breast cancer.

“Their rationale is that hormone therapy is the standard of care in these women and sentinel node surgery has shown no impact on local regional recurrence or breast cancer mortality,” said Dr. Welsh. “Therefore it would be safe to treat this population without any axillary node staging.”

She noted that the average 70-year-old woman may live another 14-16 years. “So the question is, how should we be applying the Choosing Wisely guidelines?”

Dr. Welsh and her colleagues evaluated the factors that might be impacting nodal positivity in this population, and in particular, they looked at T stage and tumor grade.

They used two large databases to identify all women over the age of 70 years with HR+ cN0 invasive disease in the institutional breast surgery database (IBSD, 2008-2016) from the Mayo Clinic and the National Cancer Database (NCDB, 2004-2013).

The rates of patients who were node positive (pN+) were based on those who had undergone axillary surgery.

The researchers then stratified patients by clinical T stage and tumor grade to compare risk of pN+ across strata.

Of 705 selected patients in the IBSD, 191 or 14.3% were pN+ and a similar rate was observed in the NCDB; 15.2% (19,607/129,216). Tumor grade and clinical T stage were associated with pN+.

“The overall rates were about 14% for both databases, and when we stratified this by T stage, we could see increasing node positivity with increasing T stage,” said Dr. Welsh.

In similar fashion, the researchers observed comparable increases when they stratified it by grade. “Increasing grades were associated with increasing rates, especially for grade 2 and higher,” said Dr. Welsh.

When the two factors were combined, the researchers were able to define low-risk criteria as clinical T1a-b, grade 1-2 or clinical T1c, grade 1. The low-risk group accounted for 54.3% (IBSD) and 43.2% (NCDB) of patients, and pN+ rates within this group were 7.6% (IBSD) and 7.4% (NCDB).

Patients outside of this subcohort had pN+ rates of 22.4% (IBSD) and 23.0% (NCDB), which extrapolated to a relative risk of 2.95 (95% CI: 1.97-4.42) and 3.11 (95% CI: 2.99-3.23), respectively (each P less than .001).

“Women in the high-risk group had three times the risk of node positivity as the low-risk group,” she said. “Based on our data, we can say that for grade 1 T1a-c we can omit sentinel node surgery, and also for grade 2 T1 a-b.”

But for grade 3, T2 or higher, or any grade 2 Tc tumors, clinicians should continue to consider sentinel node surgery, taking into account individual patient factors.

The investigator had no disclosures.

SEATTLE – Venous thromboembolism (VTE) is common in cancer, but 10% of asymptomatic patients undergoing major oncologic surgery have a preoperative VTE, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

The incidence of preoperative VTE was associated with increasing age, a history of previous VTE, and a diagnosis of sepsis 1 month prior to undergoing oncologic surgery.

Surprisingly, noted study author Dr. Melanie Gainsbury of Cedar’s Sinai Medical Center, Los Angeles, it was not associated with oncologic factors such as locally recurrent disease, metastatic disease, or the receipt of neoadjuvant therapy.

“One may argue that patients undergoing oncologic surgery should receive preoperative lower-extremity duplex screening,” especially those who appear to be at high risk, she said.

About one in five cases of VTE is cancer related, and postoperative VTE is a leading cause of morbidity in cancer patients. However, Dr. Gainsbury noted, the incidence of preoperative VTE has not been well established or studied.

In this study, she and her colleagues evaluated the prevalence and risk factors associated with preoperative VTE in asymptomatic patients who were undergoing major oncologic surgery at an academic medical center.

In their retrospective analysis, the investigators identified 412 patients from the hospital’s database who underwent open abdominopelvic oncologic surgery between 2009 to 2016. All patients in the cohort had received a preoperative lower-extremity venous duplex scan (VDS).

The authors found that the overall incidence of preoperative VTE detected on VDS in this asymptomatic population was 10.1%. Of this group, 48.6% of the VTEs were acute, 42.9% were chronic, and a small subset (8.5%) was classified as subacute.

The majority of VTEs (62.9%) were located below the knee, and all of those patients with above-the-knee VTEs (37.1%) received inferior vena cava filters prior to surgery.

None of the patients in this cohort experienced a postoperative pulmonary embolism.

The investigators also looked at various risk factors that could predispose patients to a higher risk of developing a VTE. They did not find any statistically significant differences between those with a preoperative VTE and those without one when looking at gender, body mass index, or cancer type.

There was, however, a statistically significant difference in age, with older age being significantly associated with preoperative VTE. Further analysis showed that patients were 1.3 times more likely to have a preoperative DVT for every 5-year increase in age (odds ratio, 1.3; 95% confidence interval, 1.1-1.6).

In addition, patients with preoperative VTEs were significantly more likely to experience postoperative complications, with an almost twofold increased incidence (25.7% vs. 13.2%, P = .046).

“Patients with preoperative VTE were 1.95 times more likely to develop a postoperative complication than patients without a preoperative VTE,” Dr. Gainsbury said.

In terms of comorbidities, there was no statistically significant difference in regards to history of a known lung disease, varicose veins, a known coagulation mutation, congestive heart failure, and inflammatory bowel disease.

There were also no statistical differences between hormone use or anticoagulants in patients with and without VTEs.

Of note, a recent history of sepsis appeared to be an important factor that put patients at risk for a subsequent VTE. “The preoperative VTE group had a higher rate of diagnosed sepsis during the month prior to surgery,” she said. “We believe that the preoperative diagnosis of sepsis represents a prior hospitalization and perhaps a sicker population at risk for VTEs.”

There was no funding source disclosed in the abstract. Dr. Gainsbury and her coauthors had no disclosures.

[email protected]

SEATTLE – Venous thromboembolism (VTE) is common in cancer, but 10% of asymptomatic patients undergoing major oncologic surgery have a preoperative VTE, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

The incidence of preoperative VTE was associated with increasing age, a history of previous VTE, and a diagnosis of sepsis 1 month prior to undergoing oncologic surgery.

Surprisingly, noted study author Dr. Melanie Gainsbury of Cedar’s Sinai Medical Center, Los Angeles, it was not associated with oncologic factors such as locally recurrent disease, metastatic disease, or the receipt of neoadjuvant therapy.

“One may argue that patients undergoing oncologic surgery should receive preoperative lower-extremity duplex screening,” especially those who appear to be at high risk, she said.

About one in five cases of VTE is cancer related, and postoperative VTE is a leading cause of morbidity in cancer patients. However, Dr. Gainsbury noted, the incidence of preoperative VTE has not been well established or studied.

In this study, she and her colleagues evaluated the prevalence and risk factors associated with preoperative VTE in asymptomatic patients who were undergoing major oncologic surgery at an academic medical center.

In their retrospective analysis, the investigators identified 412 patients from the hospital’s database who underwent open abdominopelvic oncologic surgery between 2009 to 2016. All patients in the cohort had received a preoperative lower-extremity venous duplex scan (VDS).

The authors found that the overall incidence of preoperative VTE detected on VDS in this asymptomatic population was 10.1%. Of this group, 48.6% of the VTEs were acute, 42.9% were chronic, and a small subset (8.5%) was classified as subacute.

The majority of VTEs (62.9%) were located below the knee, and all of those patients with above-the-knee VTEs (37.1%) received inferior vena cava filters prior to surgery.

None of the patients in this cohort experienced a postoperative pulmonary embolism.

The investigators also looked at various risk factors that could predispose patients to a higher risk of developing a VTE. They did not find any statistically significant differences between those with a preoperative VTE and those without one when looking at gender, body mass index, or cancer type.

There was, however, a statistically significant difference in age, with older age being significantly associated with preoperative VTE. Further analysis showed that patients were 1.3 times more likely to have a preoperative DVT for every 5-year increase in age (odds ratio, 1.3; 95% confidence interval, 1.1-1.6).

In addition, patients with preoperative VTEs were significantly more likely to experience postoperative complications, with an almost twofold increased incidence (25.7% vs. 13.2%, P = .046).

“Patients with preoperative VTE were 1.95 times more likely to develop a postoperative complication than patients without a preoperative VTE,” Dr. Gainsbury said.

In terms of comorbidities, there was no statistically significant difference in regards to history of a known lung disease, varicose veins, a known coagulation mutation, congestive heart failure, and inflammatory bowel disease.

There were also no statistical differences between hormone use or anticoagulants in patients with and without VTEs.

Of note, a recent history of sepsis appeared to be an important factor that put patients at risk for a subsequent VTE. “The preoperative VTE group had a higher rate of diagnosed sepsis during the month prior to surgery,” she said. “We believe that the preoperative diagnosis of sepsis represents a prior hospitalization and perhaps a sicker population at risk for VTEs.”

There was no funding source disclosed in the abstract. Dr. Gainsbury and her coauthors had no disclosures.

[email protected]

SEATTLE – Venous thromboembolism (VTE) is common in cancer, but 10% of asymptomatic patients undergoing major oncologic surgery have a preoperative VTE, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

The incidence of preoperative VTE was associated with increasing age, a history of previous VTE, and a diagnosis of sepsis 1 month prior to undergoing oncologic surgery.

Surprisingly, noted study author Dr. Melanie Gainsbury of Cedar’s Sinai Medical Center, Los Angeles, it was not associated with oncologic factors such as locally recurrent disease, metastatic disease, or the receipt of neoadjuvant therapy.

“One may argue that patients undergoing oncologic surgery should receive preoperative lower-extremity duplex screening,” especially those who appear to be at high risk, she said.

About one in five cases of VTE is cancer related, and postoperative VTE is a leading cause of morbidity in cancer patients. However, Dr. Gainsbury noted, the incidence of preoperative VTE has not been well established or studied.

In this study, she and her colleagues evaluated the prevalence and risk factors associated with preoperative VTE in asymptomatic patients who were undergoing major oncologic surgery at an academic medical center.

In their retrospective analysis, the investigators identified 412 patients from the hospital’s database who underwent open abdominopelvic oncologic surgery between 2009 to 2016. All patients in the cohort had received a preoperative lower-extremity venous duplex scan (VDS).

The authors found that the overall incidence of preoperative VTE detected on VDS in this asymptomatic population was 10.1%. Of this group, 48.6% of the VTEs were acute, 42.9% were chronic, and a small subset (8.5%) was classified as subacute.

The majority of VTEs (62.9%) were located below the knee, and all of those patients with above-the-knee VTEs (37.1%) received inferior vena cava filters prior to surgery.

None of the patients in this cohort experienced a postoperative pulmonary embolism.

The investigators also looked at various risk factors that could predispose patients to a higher risk of developing a VTE. They did not find any statistically significant differences between those with a preoperative VTE and those without one when looking at gender, body mass index, or cancer type.

There was, however, a statistically significant difference in age, with older age being significantly associated with preoperative VTE. Further analysis showed that patients were 1.3 times more likely to have a preoperative DVT for every 5-year increase in age (odds ratio, 1.3; 95% confidence interval, 1.1-1.6).

In addition, patients with preoperative VTEs were significantly more likely to experience postoperative complications, with an almost twofold increased incidence (25.7% vs. 13.2%, P = .046).

“Patients with preoperative VTE were 1.95 times more likely to develop a postoperative complication than patients without a preoperative VTE,” Dr. Gainsbury said.

In terms of comorbidities, there was no statistically significant difference in regards to history of a known lung disease, varicose veins, a known coagulation mutation, congestive heart failure, and inflammatory bowel disease.

There were also no statistical differences between hormone use or anticoagulants in patients with and without VTEs.

Of note, a recent history of sepsis appeared to be an important factor that put patients at risk for a subsequent VTE. “The preoperative VTE group had a higher rate of diagnosed sepsis during the month prior to surgery,” she said. “We believe that the preoperative diagnosis of sepsis represents a prior hospitalization and perhaps a sicker population at risk for VTEs.”

There was no funding source disclosed in the abstract. Dr. Gainsbury and her coauthors had no disclosures.

[email protected]

SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.

According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.

Courtesy Wikimedia Commons/nephron/Creative Commons License

SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.

According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.

Courtesy Wikimedia Commons/nephron/Creative Commons License

SEATTLE – Improvements in diagnosis and treatment have lengthened the survival time of patients with colorectal cancer, but the majority of deaths from CRC occur within the first 5 years.

According to new findings presented at the annual Society of Surgical Oncology Cancer Symposium, CRC as a cause of death is surpassed by cardiovascular disease (CVD) and second primary cancers as time goes on.

Courtesy Wikimedia Commons/nephron/Creative Commons License

Clinical outcomes for neoadjuvant chemotherapy (NAC) vary by molecular subtype in muscle-invasive bladder cancer, investigators report.

Researchers classified the subtypes in 223 patients with muscle-invasive bladder cancer (luminal, basal, claudin-low, and luminal-infiltrated) and found response to neoadjuvant cisplatin-based chemotherapy varied by subtype (P = .0001).

“Neoadjuvant chemotherapy improves outcomes in muscle-invasive bladder cancer, but only at 5%-7% for overall survival at 5 years,” study author Roland Seiler, MD, of the University of British Columbia, Vancouver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “About 60% of patients still have invasive disease at cystectomy so they are therefore nonresponders, but they still suffer from unnecessary side effects.”

Dr. Seiler explained that molecular subtypes of muscle-invasive bladder cancers had been identified that were based on gene expression. They decided to investigate the impact of different subtyping methods on patient response to NAC with the goal of developing a single sample model for subtyping.

A transcriptome-wide microarray analysis was conducted, using bladder tumor transurethral resection specimens that were obtained from 223 patients prior to receipt of NAC and cystectomy. The specimens were then classified according to four published methods for molecular subtype: University of North Carolina (UNC) dataset, MD Anderson (MDA) dataset, The Cancer Genome Atlas (TCGA) dataset, and the Lund dataset.

A validation set of 82 pre-NAC specimens also was done, with the results compared to non-NAC cohorts in the public domain including 179 cases from TCGA dataset, 107 from the MDA dataset, and 190 from the Lund dataset.

Finally, a genomic classifier was trained to predict the different subtypes in a single sample model and was then validated in both independent NAC and non-NAC datasets.

Investigators found that patients with luminal tumors had the best overall survival and it was independent of NAC. Patients with tumors classified as UNC basal, MDA basal, and TCGA cluster III achieved the greatest improvement in overall survival following NAC as compared with cystectomy alone.

Patients with tumors that were classified as UNC basal, MDA basal and TCGA cluster III achieved the greatest survival benefit following NAC, compared to surgery alone. Tumors that were assigned as UNC claudin-low had the worst overall survival regardless of the type of treatment regimen (P = .005).

“Basal tumors showed the most improvement with neoadjuvant therapy and should be prioritized with this treatment,” said Dr. Seiler. “Whereas for other subtypes we may need novel therapies.”

As discussant for the presentation, Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York, said that cisplatin “is a toxic therapy and we would love to have a great biomarker to select the right group of patients. Currently using present data, anywhere from 10 to 20 patients need to be treated to save one life.”

He reiterated that these findings confirm that basal tumors appear to benefit significantly from platinum-based chemotherapy and this benefit appears to exist regardless of downstaging.

“However it does not automatically follow that other subtypes do not benefit, and we are not ready to change clinical practice just yet,” Dr. Rosenberg said. “We need to prospectively validate these findings before we implement them into clinical practice.”

Clinical outcomes for neoadjuvant chemotherapy (NAC) vary by molecular subtype in muscle-invasive bladder cancer, investigators report.

Researchers classified the subtypes in 223 patients with muscle-invasive bladder cancer (luminal, basal, claudin-low, and luminal-infiltrated) and found response to neoadjuvant cisplatin-based chemotherapy varied by subtype (P = .0001).

“Neoadjuvant chemotherapy improves outcomes in muscle-invasive bladder cancer, but only at 5%-7% for overall survival at 5 years,” study author Roland Seiler, MD, of the University of British Columbia, Vancouver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “About 60% of patients still have invasive disease at cystectomy so they are therefore nonresponders, but they still suffer from unnecessary side effects.”

Dr. Seiler explained that molecular subtypes of muscle-invasive bladder cancers had been identified that were based on gene expression. They decided to investigate the impact of different subtyping methods on patient response to NAC with the goal of developing a single sample model for subtyping.

A transcriptome-wide microarray analysis was conducted, using bladder tumor transurethral resection specimens that were obtained from 223 patients prior to receipt of NAC and cystectomy. The specimens were then classified according to four published methods for molecular subtype: University of North Carolina (UNC) dataset, MD Anderson (MDA) dataset, The Cancer Genome Atlas (TCGA) dataset, and the Lund dataset.

A validation set of 82 pre-NAC specimens also was done, with the results compared to non-NAC cohorts in the public domain including 179 cases from TCGA dataset, 107 from the MDA dataset, and 190 from the Lund dataset.

Finally, a genomic classifier was trained to predict the different subtypes in a single sample model and was then validated in both independent NAC and non-NAC datasets.

Investigators found that patients with luminal tumors had the best overall survival and it was independent of NAC. Patients with tumors classified as UNC basal, MDA basal, and TCGA cluster III achieved the greatest improvement in overall survival following NAC as compared with cystectomy alone.

Patients with tumors that were classified as UNC basal, MDA basal and TCGA cluster III achieved the greatest survival benefit following NAC, compared to surgery alone. Tumors that were assigned as UNC claudin-low had the worst overall survival regardless of the type of treatment regimen (P = .005).

“Basal tumors showed the most improvement with neoadjuvant therapy and should be prioritized with this treatment,” said Dr. Seiler. “Whereas for other subtypes we may need novel therapies.”

As discussant for the presentation, Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York, said that cisplatin “is a toxic therapy and we would love to have a great biomarker to select the right group of patients. Currently using present data, anywhere from 10 to 20 patients need to be treated to save one life.”

He reiterated that these findings confirm that basal tumors appear to benefit significantly from platinum-based chemotherapy and this benefit appears to exist regardless of downstaging.

“However it does not automatically follow that other subtypes do not benefit, and we are not ready to change clinical practice just yet,” Dr. Rosenberg said. “We need to prospectively validate these findings before we implement them into clinical practice.”

Clinical outcomes for neoadjuvant chemotherapy (NAC) vary by molecular subtype in muscle-invasive bladder cancer, investigators report.

Researchers classified the subtypes in 223 patients with muscle-invasive bladder cancer (luminal, basal, claudin-low, and luminal-infiltrated) and found response to neoadjuvant cisplatin-based chemotherapy varied by subtype (P = .0001).

“Neoadjuvant chemotherapy improves outcomes in muscle-invasive bladder cancer, but only at 5%-7% for overall survival at 5 years,” study author Roland Seiler, MD, of the University of British Columbia, Vancouver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “About 60% of patients still have invasive disease at cystectomy so they are therefore nonresponders, but they still suffer from unnecessary side effects.”

Dr. Seiler explained that molecular subtypes of muscle-invasive bladder cancers had been identified that were based on gene expression. They decided to investigate the impact of different subtyping methods on patient response to NAC with the goal of developing a single sample model for subtyping.

A transcriptome-wide microarray analysis was conducted, using bladder tumor transurethral resection specimens that were obtained from 223 patients prior to receipt of NAC and cystectomy. The specimens were then classified according to four published methods for molecular subtype: University of North Carolina (UNC) dataset, MD Anderson (MDA) dataset, The Cancer Genome Atlas (TCGA) dataset, and the Lund dataset.

A validation set of 82 pre-NAC specimens also was done, with the results compared to non-NAC cohorts in the public domain including 179 cases from TCGA dataset, 107 from the MDA dataset, and 190 from the Lund dataset.

Finally, a genomic classifier was trained to predict the different subtypes in a single sample model and was then validated in both independent NAC and non-NAC datasets.

Investigators found that patients with luminal tumors had the best overall survival and it was independent of NAC. Patients with tumors classified as UNC basal, MDA basal, and TCGA cluster III achieved the greatest improvement in overall survival following NAC as compared with cystectomy alone.

Patients with tumors that were classified as UNC basal, MDA basal and TCGA cluster III achieved the greatest survival benefit following NAC, compared to surgery alone. Tumors that were assigned as UNC claudin-low had the worst overall survival regardless of the type of treatment regimen (P = .005).

“Basal tumors showed the most improvement with neoadjuvant therapy and should be prioritized with this treatment,” said Dr. Seiler. “Whereas for other subtypes we may need novel therapies.”

As discussant for the presentation, Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York, said that cisplatin “is a toxic therapy and we would love to have a great biomarker to select the right group of patients. Currently using present data, anywhere from 10 to 20 patients need to be treated to save one life.”

He reiterated that these findings confirm that basal tumors appear to benefit significantly from platinum-based chemotherapy and this benefit appears to exist regardless of downstaging.

“However it does not automatically follow that other subtypes do not benefit, and we are not ready to change clinical practice just yet,” Dr. Rosenberg said. “We need to prospectively validate these findings before we implement them into clinical practice.”

For the first time, new-onset connective tissue disease has been reported in patients who were treated with anti-PD1/PDL-1 agents, according to findings published in the Annals of the Rheumatic Diseases.

In a cohort of 447 cancer patients who received therapy with immune checkpoint inhibitors (ICIs), Sébastien Le Burel, MD, of the Bicêtre Hospital in Le Kremlin-Bicêtre, France, and his colleagues described four patients who developed a connective tissue disease (CTD). There were two cases of Sjögren’s syndrome in patients taking an anti–programmed cell death 1 (anti-PD1) drug, one case of cryoglobulinemic vasculitis as a complication of suspected Sjögren’s syndrome in a patient taking an anti–programmed cell death ligand 1 (PDL-1) agent, and a case of a patient with antinuclear antibody positive myositis who was taking an anti-PDL-1 drug (Ann Rheum Dis. 2017 Feb 27. doi: 10.1136/annrheumdis-2016-210820).

“While the onset of systemic autoimmune disease after ICI treatment remains uncommon, greater awareness of these conditions should enable physicians to provide more effective patient care,” the investigators wrote. “This underlines the need for close collaboration within a network of oncologists and other specialist physicians in the new era of immunotherapy.”

The investigators discovered the cases by screening the French prospective, multicenter, academic REISAMIC registry for reports of CTD among patients being treated with anti-PD1 or anti-PDL-1 agents.

All four of the patients who developed a CTD had metastatic cancer, and their mean age was 62 years. Two patients had been treated with anti-PD1 agents and two with anti-PDL-1 agents. None of the four patients had presented with symptoms of CTD before they began treatment.

The mean time interval between the first treatment dose and the first symptom of CTD was 60 days (range, 24-72), and the mean time interval between the first symptom and subsequent diagnosis of CTD was 40 days (range, 10-74).

Three patients discontinued the ICI agent, and two patients were treated with steroids (1 mg/kg/day).

The estimated prevalence of CTD was 0.7% in the REISAMIC registry, and the authors emphasize that the high proportion of cases of Sjögren’s syndrome is noteworthy, with two of the patients fulfilling the recent American College of Rheumatology/European League Against Rheumatism criteria for Sjögren’s syndrome.

A limitation of the study is that some patients presenting with milder symptoms might not have been investigated by their oncologist.

The findings raise the question of whether asymptomatic patients taking ICIs who are at risk for immune-related adverse events should be screened and monitored closely, the authors explained.

One of the study authors received research funding from Novartis and Pfizer for the current paper. Several authors report relationships with industry.

[email protected]

For the first time, new-onset connective tissue disease has been reported in patients who were treated with anti-PD1/PDL-1 agents, according to findings published in the Annals of the Rheumatic Diseases.

In a cohort of 447 cancer patients who received therapy with immune checkpoint inhibitors (ICIs), Sébastien Le Burel, MD, of the Bicêtre Hospital in Le Kremlin-Bicêtre, France, and his colleagues described four patients who developed a connective tissue disease (CTD). There were two cases of Sjögren’s syndrome in patients taking an anti–programmed cell death 1 (anti-PD1) drug, one case of cryoglobulinemic vasculitis as a complication of suspected Sjögren’s syndrome in a patient taking an anti–programmed cell death ligand 1 (PDL-1) agent, and a case of a patient with antinuclear antibody positive myositis who was taking an anti-PDL-1 drug (Ann Rheum Dis. 2017 Feb 27. doi: 10.1136/annrheumdis-2016-210820).

“While the onset of systemic autoimmune disease after ICI treatment remains uncommon, greater awareness of these conditions should enable physicians to provide more effective patient care,” the investigators wrote. “This underlines the need for close collaboration within a network of oncologists and other specialist physicians in the new era of immunotherapy.”

The investigators discovered the cases by screening the French prospective, multicenter, academic REISAMIC registry for reports of CTD among patients being treated with anti-PD1 or anti-PDL-1 agents.

All four of the patients who developed a CTD had metastatic cancer, and their mean age was 62 years. Two patients had been treated with anti-PD1 agents and two with anti-PDL-1 agents. None of the four patients had presented with symptoms of CTD before they began treatment.

The mean time interval between the first treatment dose and the first symptom of CTD was 60 days (range, 24-72), and the mean time interval between the first symptom and subsequent diagnosis of CTD was 40 days (range, 10-74).

Three patients discontinued the ICI agent, and two patients were treated with steroids (1 mg/kg/day).

The estimated prevalence of CTD was 0.7% in the REISAMIC registry, and the authors emphasize that the high proportion of cases of Sjögren’s syndrome is noteworthy, with two of the patients fulfilling the recent American College of Rheumatology/European League Against Rheumatism criteria for Sjögren’s syndrome.

A limitation of the study is that some patients presenting with milder symptoms might not have been investigated by their oncologist.

The findings raise the question of whether asymptomatic patients taking ICIs who are at risk for immune-related adverse events should be screened and monitored closely, the authors explained.

One of the study authors received research funding from Novartis and Pfizer for the current paper. Several authors report relationships with industry.

[email protected]

For the first time, new-onset connective tissue disease has been reported in patients who were treated with anti-PD1/PDL-1 agents, according to findings published in the Annals of the Rheumatic Diseases.

In a cohort of 447 cancer patients who received therapy with immune checkpoint inhibitors (ICIs), Sébastien Le Burel, MD, of the Bicêtre Hospital in Le Kremlin-Bicêtre, France, and his colleagues described four patients who developed a connective tissue disease (CTD). There were two cases of Sjögren’s syndrome in patients taking an anti–programmed cell death 1 (anti-PD1) drug, one case of cryoglobulinemic vasculitis as a complication of suspected Sjögren’s syndrome in a patient taking an anti–programmed cell death ligand 1 (PDL-1) agent, and a case of a patient with antinuclear antibody positive myositis who was taking an anti-PDL-1 drug (Ann Rheum Dis. 2017 Feb 27. doi: 10.1136/annrheumdis-2016-210820).

“While the onset of systemic autoimmune disease after ICI treatment remains uncommon, greater awareness of these conditions should enable physicians to provide more effective patient care,” the investigators wrote. “This underlines the need for close collaboration within a network of oncologists and other specialist physicians in the new era of immunotherapy.”

The investigators discovered the cases by screening the French prospective, multicenter, academic REISAMIC registry for reports of CTD among patients being treated with anti-PD1 or anti-PDL-1 agents.

All four of the patients who developed a CTD had metastatic cancer, and their mean age was 62 years. Two patients had been treated with anti-PD1 agents and two with anti-PDL-1 agents. None of the four patients had presented with symptoms of CTD before they began treatment.

The mean time interval between the first treatment dose and the first symptom of CTD was 60 days (range, 24-72), and the mean time interval between the first symptom and subsequent diagnosis of CTD was 40 days (range, 10-74).

Three patients discontinued the ICI agent, and two patients were treated with steroids (1 mg/kg/day).

The estimated prevalence of CTD was 0.7% in the REISAMIC registry, and the authors emphasize that the high proportion of cases of Sjögren’s syndrome is noteworthy, with two of the patients fulfilling the recent American College of Rheumatology/European League Against Rheumatism criteria for Sjögren’s syndrome.

A limitation of the study is that some patients presenting with milder symptoms might not have been investigated by their oncologist.

The findings raise the question of whether asymptomatic patients taking ICIs who are at risk for immune-related adverse events should be screened and monitored closely, the authors explained.

One of the study authors received research funding from Novartis and Pfizer for the current paper. Several authors report relationships with industry.

[email protected]

Mitoxantrone plus prednisone (MP) added to androgen deprivation therapy (ADT) does not improve outcomes in patients with clinically localized prostate cancer, according to the results of a large long-term multicenter clinical trial.

At a follow-up time of almost 11 years, outcomes were nearly the same whether patients had received chemotherapy and ADT or just ADT.

Overall survival was 87% in the cohort that received ADT only and 86% in the study arm that received ADT plus MP (HR 1.05 (CI 0.78, 1.42), P = .74). Recurrence-free survival was 84% in both groups (HR 0.98 (CI 0.78, 1.23), P = .83).

Disease free survival was 72% in both arms, and there was no statistical difference. Similarly, death without recurrence were also similar in both arms.

“Survival was greater than anticipated in both arms,” lead author L. Michael Glode, MD, of the University of Colorado, Denver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “There is no evidence that MP improves prostate cancer specific survival when added to 2 years of adjuvant ADT.”

There were 85 deaths in the ADT arm compared to 91 in the chemotherapy arm. Prostate cancer accounted for 18% of deaths among the patients receiving ADT only and 22% in the chemotherapy arm, but the incidence of other cancers was twice as common in the chemotherapy arm as in the ADT only arm.

“The predominant cancers were GI and lung,” said Dr. Glode, “And noncancer deaths were variable.”

Of note, MP increased the incidence of leukemia (one case in the ADT group vs. five in the chemotherapy group).

“This trial demonstrates the feasibility of doing adjuvant trials in prostate cancer post radical prostatectomy,” said Dr. Glode. “Survival was greater than anticipated in both arms.”

The assumptions of this trial were that 2 years of adjuvant ADT would improve overall survival and progression-free survival although definitive data were unavailable.

The rationale for doing a study using adjuvant therapy was based on published literature, in which findings had showed that while short-term neoadjuvant ADT prior to prostatectomy reduced positive margins, it had no effect on disease-free survival. In addition, research had shown that longer-term ADT improved outcomes for patients undergoing curative radiation therapy.

For chemotherapy, Dr. Glode pointed to data showing that adjuvant chemotherapy improved progression-free survival in patients who had undergone both prostatectomy and radiation therapy.

“We hypothesized that the addition of modestly active chemotherapy earlier in disease might improve overall survival and progression-free survival,” he said.

The primary objective was overall survival and the secondary endpoint was disease-free survival.

The S9921 trial enrolled 983 patients from October 1999 to January 2007 with clinically localized prostate cancer, before enrollment ceased because of the increased incidence of leukemia in the ADT plus MP arm.

Of this group, 22 patients were ineligible, and the remaining patients were assigned to goserelin acetate 10.8 mg plus bicalutamide 50 mg (n = 481) or the same ADT plus MP (n = 480).

The patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation, and the presurgical PSA was 7.6 ng/mL. Radiation therapy was allowed in both arms at physician discretion, and 26% intended to receive radiation therapy.

In the ADT only arm, 402 completed the treatment, and 390 completed treatment in the ADT plus chemotherapy arm.

Grade 3 or higher adverse events were more common in the chemotherapy group (56%/30%, P less than .0001). “As for toxicities, the main difference was the presence of leukopenia in the chemotherapy arm,” said Dr. Glode.

The study was funded by Southwest Oncology Group’s Urologic Cancer Outreach Program, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Clinical Trials Support Unit, and National Cancer Institute. None of the authors had disclosures.

Mitoxantrone plus prednisone (MP) added to androgen deprivation therapy (ADT) does not improve outcomes in patients with clinically localized prostate cancer, according to the results of a large long-term multicenter clinical trial.

At a follow-up time of almost 11 years, outcomes were nearly the same whether patients had received chemotherapy and ADT or just ADT.

Overall survival was 87% in the cohort that received ADT only and 86% in the study arm that received ADT plus MP (HR 1.05 (CI 0.78, 1.42), P = .74). Recurrence-free survival was 84% in both groups (HR 0.98 (CI 0.78, 1.23), P = .83).

Disease free survival was 72% in both arms, and there was no statistical difference. Similarly, death without recurrence were also similar in both arms.

“Survival was greater than anticipated in both arms,” lead author L. Michael Glode, MD, of the University of Colorado, Denver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “There is no evidence that MP improves prostate cancer specific survival when added to 2 years of adjuvant ADT.”

There were 85 deaths in the ADT arm compared to 91 in the chemotherapy arm. Prostate cancer accounted for 18% of deaths among the patients receiving ADT only and 22% in the chemotherapy arm, but the incidence of other cancers was twice as common in the chemotherapy arm as in the ADT only arm.

“The predominant cancers were GI and lung,” said Dr. Glode, “And noncancer deaths were variable.”

Of note, MP increased the incidence of leukemia (one case in the ADT group vs. five in the chemotherapy group).

“This trial demonstrates the feasibility of doing adjuvant trials in prostate cancer post radical prostatectomy,” said Dr. Glode. “Survival was greater than anticipated in both arms.”

The assumptions of this trial were that 2 years of adjuvant ADT would improve overall survival and progression-free survival although definitive data were unavailable.

The rationale for doing a study using adjuvant therapy was based on published literature, in which findings had showed that while short-term neoadjuvant ADT prior to prostatectomy reduced positive margins, it had no effect on disease-free survival. In addition, research had shown that longer-term ADT improved outcomes for patients undergoing curative radiation therapy.

For chemotherapy, Dr. Glode pointed to data showing that adjuvant chemotherapy improved progression-free survival in patients who had undergone both prostatectomy and radiation therapy.

“We hypothesized that the addition of modestly active chemotherapy earlier in disease might improve overall survival and progression-free survival,” he said.

The primary objective was overall survival and the secondary endpoint was disease-free survival.

The S9921 trial enrolled 983 patients from October 1999 to January 2007 with clinically localized prostate cancer, before enrollment ceased because of the increased incidence of leukemia in the ADT plus MP arm.

Of this group, 22 patients were ineligible, and the remaining patients were assigned to goserelin acetate 10.8 mg plus bicalutamide 50 mg (n = 481) or the same ADT plus MP (n = 480).

The patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation, and the presurgical PSA was 7.6 ng/mL. Radiation therapy was allowed in both arms at physician discretion, and 26% intended to receive radiation therapy.

In the ADT only arm, 402 completed the treatment, and 390 completed treatment in the ADT plus chemotherapy arm.

Grade 3 or higher adverse events were more common in the chemotherapy group (56%/30%, P less than .0001). “As for toxicities, the main difference was the presence of leukopenia in the chemotherapy arm,” said Dr. Glode.

The study was funded by Southwest Oncology Group’s Urologic Cancer Outreach Program, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Clinical Trials Support Unit, and National Cancer Institute. None of the authors had disclosures.

Mitoxantrone plus prednisone (MP) added to androgen deprivation therapy (ADT) does not improve outcomes in patients with clinically localized prostate cancer, according to the results of a large long-term multicenter clinical trial.

At a follow-up time of almost 11 years, outcomes were nearly the same whether patients had received chemotherapy and ADT or just ADT.

Overall survival was 87% in the cohort that received ADT only and 86% in the study arm that received ADT plus MP (HR 1.05 (CI 0.78, 1.42), P = .74). Recurrence-free survival was 84% in both groups (HR 0.98 (CI 0.78, 1.23), P = .83).

Disease free survival was 72% in both arms, and there was no statistical difference. Similarly, death without recurrence were also similar in both arms.

“Survival was greater than anticipated in both arms,” lead author L. Michael Glode, MD, of the University of Colorado, Denver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “There is no evidence that MP improves prostate cancer specific survival when added to 2 years of adjuvant ADT.”

There were 85 deaths in the ADT arm compared to 91 in the chemotherapy arm. Prostate cancer accounted for 18% of deaths among the patients receiving ADT only and 22% in the chemotherapy arm, but the incidence of other cancers was twice as common in the chemotherapy arm as in the ADT only arm.

“The predominant cancers were GI and lung,” said Dr. Glode, “And noncancer deaths were variable.”

Of note, MP increased the incidence of leukemia (one case in the ADT group vs. five in the chemotherapy group).

“This trial demonstrates the feasibility of doing adjuvant trials in prostate cancer post radical prostatectomy,” said Dr. Glode. “Survival was greater than anticipated in both arms.”

The assumptions of this trial were that 2 years of adjuvant ADT would improve overall survival and progression-free survival although definitive data were unavailable.

The rationale for doing a study using adjuvant therapy was based on published literature, in which findings had showed that while short-term neoadjuvant ADT prior to prostatectomy reduced positive margins, it had no effect on disease-free survival. In addition, research had shown that longer-term ADT improved outcomes for patients undergoing curative radiation therapy.

For chemotherapy, Dr. Glode pointed to data showing that adjuvant chemotherapy improved progression-free survival in patients who had undergone both prostatectomy and radiation therapy.

“We hypothesized that the addition of modestly active chemotherapy earlier in disease might improve overall survival and progression-free survival,” he said.

The primary objective was overall survival and the secondary endpoint was disease-free survival.

The S9921 trial enrolled 983 patients from October 1999 to January 2007 with clinically localized prostate cancer, before enrollment ceased because of the increased incidence of leukemia in the ADT plus MP arm.

Of this group, 22 patients were ineligible, and the remaining patients were assigned to goserelin acetate 10.8 mg plus bicalutamide 50 mg (n = 481) or the same ADT plus MP (n = 480).

The patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation, and the presurgical PSA was 7.6 ng/mL. Radiation therapy was allowed in both arms at physician discretion, and 26% intended to receive radiation therapy.

In the ADT only arm, 402 completed the treatment, and 390 completed treatment in the ADT plus chemotherapy arm.

Grade 3 or higher adverse events were more common in the chemotherapy group (56%/30%, P less than .0001). “As for toxicities, the main difference was the presence of leukopenia in the chemotherapy arm,” said Dr. Glode.

The study was funded by Southwest Oncology Group’s Urologic Cancer Outreach Program, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Clinical Trials Support Unit, and National Cancer Institute. None of the authors had disclosures.

ORLANDO – In the largest assessment to date of circulating tumor DNA (ctDNA) in patients with metastatic renal cell carcinoma (mRCC), the majority of patients were found to have clinically relevant genomic alterations.

The most frequently occurring alterations for the entire cohort were TP53, VHL, NF1, EGFR, and ARID1A, but, importantly, the genetic profiles differed between patients receiving first-line therapy and those receiving second-line treatments.

“Compared to patients receiving first-line therapy, patients receiving post–first-line agents had increased genomic alterations in TP53, NF1, EGFR, and PIK3CA,” said lead study author Sumanta K. Pal, MD, a urologic oncologist at City of Hope, Duarte, Calif.

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal, who presented the findings of his study in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology..

Several targeted therapies have been approved for mRCC, including vascular endothelial growth factor–targeted therapies, mammalian target of rapamycin inhibitors, and checkpoint inhibitors. However, treatment of mRCC is generally distinctly different for the first- and second-line settings.

Dr. Pal noted that, while “efforts such as the TCGA [The Cancer Genome Atlas] have shed some light on the tumor biology, it is important to keep in mind that these datasets reflect earlier stages of disease. Certainly, there may be an evolution of tumor biology as patients progress toward metastasis.”

Circulating tumor markers represent a practical means of serially assessing tumor biology, and ctDNA can account for tumor heterogeneity. In this study, the authors sought to determine the mutational landscape of mRCC as well as to assess changes across patients receiving first-line and subsequent therapies by using ctDNA.

Data were obtained from 224 patients who received ctDNA profiling at progression as part of routine clinical care using Guardant360, a CLIA-certified comprehensive plasma assay that evaluated 70 genes. Of this group, 64 and 56 patients were coded as receiving frontline and post–first-line agents, respectively.

Genomic alterations were pooled for the entire group, and first and second (subsequent) therapies were compared, based on conventional practice patterns (first-line regimens included sunitinib, pazopanib and bevacizumab, and second line included everolimus, axitinib, cabozantinib, and nivolumab).

Genomic alterations were found in 78.6% of patients, with an average of 3.3 genomic alterations per patient. For patients receiving first-line therapy, the average number of ctDNA alterations was 2.9, compared with 3.7 for those in the cohort who were receiving second-line therapy. The median (range) ctDNA variant allele fractions were 0.23 (0.05-9.92) in the first-line group and 0.24 (0.04-47.14) in second line.

The authors observed that there were disparities in genomic alterations between both patient cohorts, with the highest disparity seen in (second vs. first line) TP53 (49% vs. 25%), VHL (29% vs. 25%), NF1 (20% vs. 15%), EGFR (17% vs. 21%), and PIK3CA (17% vs. 8%).

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal.

He also pointed out that there were significant differences between the current dataset and other published reports, which may reflect the advanced state of the disease of the patients in this study.

Efforts are also ongoing to add detailed data on demographics and clinical outcomes to the current dataset, Dr. Pal added.

Acting as the paper’s discussant, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center pointed out that as there are no validated biomarkers of drug resistance or tumor evolution and that liquid biopsy offers a potential platform.

The use of ctDNA is a “convenient technology that offers new means to assess RCC biology,” said Dr. Lara, but the caveat is that it is “still in its infancy and has no immediate clinical application.”

The current study is “hypothesis generating only.” ctDNA changes need to be related to outcome following treatment, and the functional role of genomic alterations in RCC biology must be validated, he said.

ORLANDO – In the largest assessment to date of circulating tumor DNA (ctDNA) in patients with metastatic renal cell carcinoma (mRCC), the majority of patients were found to have clinically relevant genomic alterations.

The most frequently occurring alterations for the entire cohort were TP53, VHL, NF1, EGFR, and ARID1A, but, importantly, the genetic profiles differed between patients receiving first-line therapy and those receiving second-line treatments.

“Compared to patients receiving first-line therapy, patients receiving post–first-line agents had increased genomic alterations in TP53, NF1, EGFR, and PIK3CA,” said lead study author Sumanta K. Pal, MD, a urologic oncologist at City of Hope, Duarte, Calif.

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal, who presented the findings of his study in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology..

Several targeted therapies have been approved for mRCC, including vascular endothelial growth factor–targeted therapies, mammalian target of rapamycin inhibitors, and checkpoint inhibitors. However, treatment of mRCC is generally distinctly different for the first- and second-line settings.

Dr. Pal noted that, while “efforts such as the TCGA [The Cancer Genome Atlas] have shed some light on the tumor biology, it is important to keep in mind that these datasets reflect earlier stages of disease. Certainly, there may be an evolution of tumor biology as patients progress toward metastasis.”

Circulating tumor markers represent a practical means of serially assessing tumor biology, and ctDNA can account for tumor heterogeneity. In this study, the authors sought to determine the mutational landscape of mRCC as well as to assess changes across patients receiving first-line and subsequent therapies by using ctDNA.

Data were obtained from 224 patients who received ctDNA profiling at progression as part of routine clinical care using Guardant360, a CLIA-certified comprehensive plasma assay that evaluated 70 genes. Of this group, 64 and 56 patients were coded as receiving frontline and post–first-line agents, respectively.

Genomic alterations were pooled for the entire group, and first and second (subsequent) therapies were compared, based on conventional practice patterns (first-line regimens included sunitinib, pazopanib and bevacizumab, and second line included everolimus, axitinib, cabozantinib, and nivolumab).

Genomic alterations were found in 78.6% of patients, with an average of 3.3 genomic alterations per patient. For patients receiving first-line therapy, the average number of ctDNA alterations was 2.9, compared with 3.7 for those in the cohort who were receiving second-line therapy. The median (range) ctDNA variant allele fractions were 0.23 (0.05-9.92) in the first-line group and 0.24 (0.04-47.14) in second line.

The authors observed that there were disparities in genomic alterations between both patient cohorts, with the highest disparity seen in (second vs. first line) TP53 (49% vs. 25%), VHL (29% vs. 25%), NF1 (20% vs. 15%), EGFR (17% vs. 21%), and PIK3CA (17% vs. 8%).

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal.

He also pointed out that there were significant differences between the current dataset and other published reports, which may reflect the advanced state of the disease of the patients in this study.

Efforts are also ongoing to add detailed data on demographics and clinical outcomes to the current dataset, Dr. Pal added.

Acting as the paper’s discussant, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center pointed out that as there are no validated biomarkers of drug resistance or tumor evolution and that liquid biopsy offers a potential platform.

The use of ctDNA is a “convenient technology that offers new means to assess RCC biology,” said Dr. Lara, but the caveat is that it is “still in its infancy and has no immediate clinical application.”

The current study is “hypothesis generating only.” ctDNA changes need to be related to outcome following treatment, and the functional role of genomic alterations in RCC biology must be validated, he said.

ORLANDO – In the largest assessment to date of circulating tumor DNA (ctDNA) in patients with metastatic renal cell carcinoma (mRCC), the majority of patients were found to have clinically relevant genomic alterations.

The most frequently occurring alterations for the entire cohort were TP53, VHL, NF1, EGFR, and ARID1A, but, importantly, the genetic profiles differed between patients receiving first-line therapy and those receiving second-line treatments.

“Compared to patients receiving first-line therapy, patients receiving post–first-line agents had increased genomic alterations in TP53, NF1, EGFR, and PIK3CA,” said lead study author Sumanta K. Pal, MD, a urologic oncologist at City of Hope, Duarte, Calif.

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal, who presented the findings of his study in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology..

Several targeted therapies have been approved for mRCC, including vascular endothelial growth factor–targeted therapies, mammalian target of rapamycin inhibitors, and checkpoint inhibitors. However, treatment of mRCC is generally distinctly different for the first- and second-line settings.

Dr. Pal noted that, while “efforts such as the TCGA [The Cancer Genome Atlas] have shed some light on the tumor biology, it is important to keep in mind that these datasets reflect earlier stages of disease. Certainly, there may be an evolution of tumor biology as patients progress toward metastasis.”

Circulating tumor markers represent a practical means of serially assessing tumor biology, and ctDNA can account for tumor heterogeneity. In this study, the authors sought to determine the mutational landscape of mRCC as well as to assess changes across patients receiving first-line and subsequent therapies by using ctDNA.

Data were obtained from 224 patients who received ctDNA profiling at progression as part of routine clinical care using Guardant360, a CLIA-certified comprehensive plasma assay that evaluated 70 genes. Of this group, 64 and 56 patients were coded as receiving frontline and post–first-line agents, respectively.

Genomic alterations were pooled for the entire group, and first and second (subsequent) therapies were compared, based on conventional practice patterns (first-line regimens included sunitinib, pazopanib and bevacizumab, and second line included everolimus, axitinib, cabozantinib, and nivolumab).

Genomic alterations were found in 78.6% of patients, with an average of 3.3 genomic alterations per patient. For patients receiving first-line therapy, the average number of ctDNA alterations was 2.9, compared with 3.7 for those in the cohort who were receiving second-line therapy. The median (range) ctDNA variant allele fractions were 0.23 (0.05-9.92) in the first-line group and 0.24 (0.04-47.14) in second line.

The authors observed that there were disparities in genomic alterations between both patient cohorts, with the highest disparity seen in (second vs. first line) TP53 (49% vs. 25%), VHL (29% vs. 25%), NF1 (20% vs. 15%), EGFR (17% vs. 21%), and PIK3CA (17% vs. 8%).

“These alterations underscore potential mechanisms of resistance,” said Dr. Pal.

He also pointed out that there were significant differences between the current dataset and other published reports, which may reflect the advanced state of the disease of the patients in this study.

Efforts are also ongoing to add detailed data on demographics and clinical outcomes to the current dataset, Dr. Pal added.

Acting as the paper’s discussant, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center pointed out that as there are no validated biomarkers of drug resistance or tumor evolution and that liquid biopsy offers a potential platform.

The use of ctDNA is a “convenient technology that offers new means to assess RCC biology,” said Dr. Lara, but the caveat is that it is “still in its infancy and has no immediate clinical application.”

The current study is “hypothesis generating only.” ctDNA changes need to be related to outcome following treatment, and the functional role of genomic alterations in RCC biology must be validated, he said.