Renal Cell Carcinoma

A novel, first-in-class, agonist anti-CD27 monoclonal antibody was found to be clinically and biologically active, according to early findings published in the Journal of Clinical Oncology.

In this phase I first-in-human study of varlilumab, doses at 0.1 to 10 mg/kg were well tolerated by patients with advanced solid tumors. In addition, antitumor activity was also observed. One heavily pretreated patient with stage IV disease renal cell carcinoma (RCC) experienced durable and significant tumor regression, with 78% tumor shrinkage and a partial response that persisted for 2.3 years without additional anticancer therapy, reported Howard A. Burris, MD, of the Sarah Cannon Research Institute, Tennessee Oncology, Nashville, and his colleagues (J Clin Oncol. 2017 May 2. doi: 10.1200/JCO.2016.70.1508).

A novel, first-in-class, agonist anti-CD27 monoclonal antibody was found to be clinically and biologically active, according to early findings published in the Journal of Clinical Oncology.

In this phase I first-in-human study of varlilumab, doses at 0.1 to 10 mg/kg were well tolerated by patients with advanced solid tumors. In addition, antitumor activity was also observed. One heavily pretreated patient with stage IV disease renal cell carcinoma (RCC) experienced durable and significant tumor regression, with 78% tumor shrinkage and a partial response that persisted for 2.3 years without additional anticancer therapy, reported Howard A. Burris, MD, of the Sarah Cannon Research Institute, Tennessee Oncology, Nashville, and his colleagues (J Clin Oncol. 2017 May 2. doi: 10.1200/JCO.2016.70.1508).

A novel, first-in-class, agonist anti-CD27 monoclonal antibody was found to be clinically and biologically active, according to early findings published in the Journal of Clinical Oncology.

In this phase I first-in-human study of varlilumab, doses at 0.1 to 10 mg/kg were well tolerated by patients with advanced solid tumors. In addition, antitumor activity was also observed. One heavily pretreated patient with stage IV disease renal cell carcinoma (RCC) experienced durable and significant tumor regression, with 78% tumor shrinkage and a partial response that persisted for 2.3 years without additional anticancer therapy, reported Howard A. Burris, MD, of the Sarah Cannon Research Institute, Tennessee Oncology, Nashville, and his colleagues (J Clin Oncol. 2017 May 2. doi: 10.1200/JCO.2016.70.1508).

MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.

Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.

“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”

Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.

The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.

“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.

“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”

Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).

“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.

“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”

MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.

Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.

“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”

Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.

The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.

“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.

“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”

Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).

“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.

“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”

MIAMI BEACH – Cytoreductive debulking surgery for neuroendocrine liver metastases provides a lower but “reasonable” long-term survival, compared with curative intent surgery, according to results of a study presented at the annual meeting of the Americas Hepatico-Pancreato-Biliary Association.

Liver debulking for patients with grossly unresectable disease is therefore an option that may extend survival, the study researchers said.

“Surgical resection offers the best chance for long-term survival but may not be technically feasible for all our patients,” said Fabio Bagante, MD, a resident at the University of Verona (Italy). “Debulking neuroendocrine liver metastases has been proposed as an alternative.”

Dr. Bagante and coinvestigators compared outcomes between 180 patients who had debulking surgery (defined as an R2 outcome) and 449 who underwent curative intent resection (R0 or R1). Patients had surgery between 1990 and 2015 at eight institutions, and the primary outcome was overall survival. The mean follow-up was 51 months; during that time, 174 patients died.

The 5-year overall survival was 72% in the debulking group and 89% in the curative intent group. The 10-year overall survival was 41% in the debulking group and 77% among the curative intent surgery patients.

“Debulking operations for neuroendocrine liver metastases provide lower but reasonable long-term survival, compared with patients who underwent curative intent,” Dr. Bagante said.

“Nearly 3 in 10 patients underwent debulking surgery,” Dr. Bagante said. “It was more common among the elderly, males with symptomatic disease, and patients with greater liver involvement.”

Patients in the liver-debulking groups were also significantly more likely to have high–tumor grade disease, 35%, versus 13% of the curative intent resection group (P less than .001). They were also more likely to have metastatic disease, with an N1 rate of 73% versus 52% (P less than .001).

“Great work. Thanks for presenting this topic. It’s quite a debated topic,” said study discussant Aaron Lee, DO, of the department of general surgery at Cleveland Clinic Florida in Weston. “I looked at your data on asymptomatic patients who had a 5-year survival of 60%; U.K. data show [the] same survival without any intervention.” He asked Dr. Bagante to comment on operating on patients without any symptoms.

“Regarding the role of symptoms as a predictor of survival, there are many papers in the literature debating what are the true predictors of survival,” Dr. Bagante noted. “We don’t think [symptoms have an] impact; our data do not demonstrate that. We think the biologic behavior of the disease, the impact of the progression of the disease, and the grade of the tumor, [indicated by] Ki-67, could have more of a role.”

Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.

Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).

However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).

In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.

The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.

The authors declared that they had no conflicts of interest.

Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.

Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).

However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).

In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.

The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.

The authors declared that they had no conflicts of interest.

Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.

Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).

However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).

In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.

The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.

The authors declared that they had no conflicts of interest.

Adjuvant sunitinib or sorafenib show no significant advantages in disease-free or overall survival over placebo in patients with high-risk clear cell renal cancer, according to secondary analysis of data from the ASSURE trial.

The primary analysis of data from the ASSURE trial, which included patients with all types of renal cell carcinoma, had failed to show a benefit in disease-free survival.

“Given recently published results of a 750-patient randomized trial, S-TRAC, (sunitinib 50 mg daily [4/2 schedule] vs placebo in clear cell predominant pT3-4 or node-positive disease) that show improved [disease-free survival], the appropriate adjuvant strategy for high-risk patients is unclear,” Naomi B. Haas, MD, and coauthors wrote (JAMA Oncol. 2017 Mar 9. doi: 10.1001/jamaoncol.2017.0076).

Therefore, the investigators focused on a subset of patients from the ASSURE trial with high-risk clear cell renal cancer to determine if there might be a benefit in this group.

The secondary analysis involved 1,069 participants with pT3 and higher or node-positive renal cancer with clear cell histology who were randomized to receive 54 weeks of sunitinib (50mg, oral daily for 28 of 42 days per cycle), sorafenib (400 mg, oral twice daily continuously), or placebo.

The 5-year disease-free survival rate was 47.7% for patients in the sunitinib arm, 49.9% for those taking sorafenib, and 50% for placebo, with no statistically significant difference between the three groups. The 5-year overall survival rate was 75.2% for the sunitinib arm, 80.2% in the sorafenib arm, and 76.5% for those on placebo, with no statistically significant differences between the groups, reported Dr. Haas of the Abramson Cancer Center of the University of Pennsylvania, Philadelphia, and colleagues.

“This high-risk population had a better 5-year recurrence-free rate (around 50%) than expected (41.9% for high-risk disease and 36.0% for node-positive disease), possibly a result of better surgical technique, more accurate staging, or unknown biologic factors,” the authors wrote.

When the researchers analyzed disease-free survival according to quartiles of total dose per 6-week cycle, they also found no differences between each quartile of average dose per cycle.

There was, however, a significantly higher rate of grade 3 or higher adverse events in the sunitinib arm (66%) and sorafenib group (72%), compared with placebo (22%).

“Based on this analysis, a rationale for adjuvant therapy in this high-risk population is not elucidated,” Dr. Haas and colleagues said.

The study was coordinated by the ECOG-ACRIN Cancer Research Group and supported by Public Health Service grants, the National Cancer Institute, National Institutes of Health, and the Department of Health & Human Services. The drugs and placebos were provided by Bayer and Pfizer through the National Cancer Institute.

Adjuvant sunitinib or sorafenib show no significant advantages in disease-free or overall survival over placebo in patients with high-risk clear cell renal cancer, according to secondary analysis of data from the ASSURE trial.

The primary analysis of data from the ASSURE trial, which included patients with all types of renal cell carcinoma, had failed to show a benefit in disease-free survival.

“Given recently published results of a 750-patient randomized trial, S-TRAC, (sunitinib 50 mg daily [4/2 schedule] vs placebo in clear cell predominant pT3-4 or node-positive disease) that show improved [disease-free survival], the appropriate adjuvant strategy for high-risk patients is unclear,” Naomi B. Haas, MD, and coauthors wrote (JAMA Oncol. 2017 Mar 9. doi: 10.1001/jamaoncol.2017.0076).

Therefore, the investigators focused on a subset of patients from the ASSURE trial with high-risk clear cell renal cancer to determine if there might be a benefit in this group.

The secondary analysis involved 1,069 participants with pT3 and higher or node-positive renal cancer with clear cell histology who were randomized to receive 54 weeks of sunitinib (50mg, oral daily for 28 of 42 days per cycle), sorafenib (400 mg, oral twice daily continuously), or placebo.

The 5-year disease-free survival rate was 47.7% for patients in the sunitinib arm, 49.9% for those taking sorafenib, and 50% for placebo, with no statistically significant difference between the three groups. The 5-year overall survival rate was 75.2% for the sunitinib arm, 80.2% in the sorafenib arm, and 76.5% for those on placebo, with no statistically significant differences between the groups, reported Dr. Haas of the Abramson Cancer Center of the University of Pennsylvania, Philadelphia, and colleagues.

“This high-risk population had a better 5-year recurrence-free rate (around 50%) than expected (41.9% for high-risk disease and 36.0% for node-positive disease), possibly a result of better surgical technique, more accurate staging, or unknown biologic factors,” the authors wrote.

When the researchers analyzed disease-free survival according to quartiles of total dose per 6-week cycle, they also found no differences between each quartile of average dose per cycle.

There was, however, a significantly higher rate of grade 3 or higher adverse events in the sunitinib arm (66%) and sorafenib group (72%), compared with placebo (22%).

“Based on this analysis, a rationale for adjuvant therapy in this high-risk population is not elucidated,” Dr. Haas and colleagues said.

The study was coordinated by the ECOG-ACRIN Cancer Research Group and supported by Public Health Service grants, the National Cancer Institute, National Institutes of Health, and the Department of Health & Human Services. The drugs and placebos were provided by Bayer and Pfizer through the National Cancer Institute.

Adjuvant sunitinib or sorafenib show no significant advantages in disease-free or overall survival over placebo in patients with high-risk clear cell renal cancer, according to secondary analysis of data from the ASSURE trial.

The primary analysis of data from the ASSURE trial, which included patients with all types of renal cell carcinoma, had failed to show a benefit in disease-free survival.

“Given recently published results of a 750-patient randomized trial, S-TRAC, (sunitinib 50 mg daily [4/2 schedule] vs placebo in clear cell predominant pT3-4 or node-positive disease) that show improved [disease-free survival], the appropriate adjuvant strategy for high-risk patients is unclear,” Naomi B. Haas, MD, and coauthors wrote (JAMA Oncol. 2017 Mar 9. doi: 10.1001/jamaoncol.2017.0076).

Therefore, the investigators focused on a subset of patients from the ASSURE trial with high-risk clear cell renal cancer to determine if there might be a benefit in this group.

The secondary analysis involved 1,069 participants with pT3 and higher or node-positive renal cancer with clear cell histology who were randomized to receive 54 weeks of sunitinib (50mg, oral daily for 28 of 42 days per cycle), sorafenib (400 mg, oral twice daily continuously), or placebo.

The 5-year disease-free survival rate was 47.7% for patients in the sunitinib arm, 49.9% for those taking sorafenib, and 50% for placebo, with no statistically significant difference between the three groups. The 5-year overall survival rate was 75.2% for the sunitinib arm, 80.2% in the sorafenib arm, and 76.5% for those on placebo, with no statistically significant differences between the groups, reported Dr. Haas of the Abramson Cancer Center of the University of Pennsylvania, Philadelphia, and colleagues.

“This high-risk population had a better 5-year recurrence-free rate (around 50%) than expected (41.9% for high-risk disease and 36.0% for node-positive disease), possibly a result of better surgical technique, more accurate staging, or unknown biologic factors,” the authors wrote.

When the researchers analyzed disease-free survival according to quartiles of total dose per 6-week cycle, they also found no differences between each quartile of average dose per cycle.

There was, however, a significantly higher rate of grade 3 or higher adverse events in the sunitinib arm (66%) and sorafenib group (72%), compared with placebo (22%).

“Based on this analysis, a rationale for adjuvant therapy in this high-risk population is not elucidated,” Dr. Haas and colleagues said.

The study was coordinated by the ECOG-ACRIN Cancer Research Group and supported by Public Health Service grants, the National Cancer Institute, National Institutes of Health, and the Department of Health & Human Services. The drugs and placebos were provided by Bayer and Pfizer through the National Cancer Institute.

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.

ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.

In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.

“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.

“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.

“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.

“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”

Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.

Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added

[email protected]

ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.

In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.

“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.

“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.

“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.

“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”

Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.

Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added

[email protected]

ORLANDO – Some people with advanced kidney cancer who respond to immune checkpoint inhibitor therapy and subsequently stop because of immune-related adverse events may continue to see a clinical benefit for 6 months or longer, a retrospective, multicenter study reveals.

In fact, investigators labeled 42% of 19 patients with metastatic renal cell carcinoma (mRCC) “durable responders” to checkpoint inhibitor blockade. “What we’ve demonstrated is that, despite patients stopping their treatment, there is a subset who continue to have disease in check and controlled despite [their] not being on any therapy,” Rana R. McKay, MD, of the University of California, San Diego, said.

“Our subset was small, only 19 patients, so the next step is to validate our findings in larger study, and actually conduct a prospective trial to assess if discontinuation of therapy is worthwhile to investigate in this population,” Dr. McKay said during a press briefing prior to the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

PD-1/PDL-1 inhibitors demonstrate efficacy against an expanding list of malignancies, Dr. McKay said. The current standard is to administer these agents on a continuous basis until cancer progression or toxicity occurs. However, the study raises the possibility of intentionally discontinuing their use in some patients in the future, primarily because PD-1/PD-L1 inhibitors are associated with a wide range of side effects. Most concerning are immune-related adverse events “which are thought to be due to immune system activation,” she said.

“These drugs work to reinvigorate the immune response, and one of the unintended consequences is … they may also elicit an autoimmune response against one or more organs in the body,” said Sumanta Pal, MD, of City of Hope Medical Center in Duarte, Calif. and moderator of the press briefing.

“There was a wide spectrum of adverse events affecting different organ systems,” Dr. McKay said, “including pneumonitis, myositis, nephritis, hepatitis, pericarditis, and myocarditis, just to name a few.” A total of 84% of patients required steroids to treat immune-related adverse events, 11% needed additional immunosuppressant agents to treat their symptoms, and 53% have ongoing toxicity.

“If a patient has immune-related side effects, the impact can be serious,” Dr. Pal said. “This [study] certainly supports the premise that those individuals who experience immune related side effects could have a tangible benefit from the drug nonetheless.”

Median patient age was 68 years, 74% were male and 26% had aggressive disease. In the durable responders group, the median time on treatment was 11 months and median time off treatment was 20 months. In contrast, the patients whose cancer worsened immediately after therapy cessation were treated a median 4 months and were off treatment a median of only 2 months. A total of 63% received either PD-1 or PD-L1 monotherapy and the remainder received one of these inhibitors in combination with other systemic therapies.

Prospective studies are warranted to determine approaches to customize immunotherapy based on response, Dr. McKay said. A phase II study is planned to assess optimized management of nivolumab therapy based on response in patients with mRCC, she added

[email protected]

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Patients with metastatic renal cell carcinoma (mRCC) who experience disease progression in one or more metastatic sites while on treatment with a targeted therapy may still benefit from staying on the same drug rather than switching to another following locoregional treatment, results of a retrospective study suggest.

Among 55 patients with RCC, those who continued on the same targeted therapy after locoregional treatment of a site of progression had significantly longer post–first oligoprogression overall survival (PFOPOS) than patients who had been switched to another targeted agent, reported Della De Lisi, MD, from the University of Rome and colleagues.

“Locoregional treatments represent an option for oligometastatic mRCC treated with targeted therapy. Continuing the same systemic treatment after radical locoregional treatment in one or more metastatic site[s] appear[s] to be an independent predictive factor of better outcome in this subset of patients. Bone oligoprogressive mRCC showed similar better outcome[s].” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

One option for patients with mRCC with slow or limited metastatic progression is locoregional therapy with radical intent, with the goal of achieving a complete response. When a patient’s disease progresses while on a targeted agent such as sorafenib (Nexavar) or sunitinib(Sutent), he or she may be switched to a different agent, but there is a lack of data on outcomes with this strategy, the authors said.

To see whether sticking with the same therapy or switching to another could be the wiser course, they took a retrospective look at outcomes for 55 patients with mRCC who had disease progression after at least 6 months of a first-line therapy in one or more sites treated radically with locoregional therapy.

The majority of patients (52 of 55; 94.5%) had clear-cell histology tumors. Slightly more than half (31 patients, 56.4%) had good risk disease according to the Memorial Sloan Kettering Cancer Center kidney cancer risk prediction tool, and 23 (41.8%) had intermediate risk. The risk category was not calculable for the one remaining patient.

In all, 36 patients (65.5%) did not have evidence of metastasis at diagnosis. All patients had oligoprogression in a single site. The most common metastatic sites were to lung in 15 patients, bone in 10, kidney in 8, brain in 4, and liver in 4 (other sites not listed).

Forty-eight patients received sunitinib in the first line, five received pazopanib (Votrient), and two received sorafenib. Locoregional therapy at the site of progression was radiotherapy in 25 patients (45.5%), surgery in 25, and cryoablation or thermoablation in 5.

The majority of patients (48; 83.6%) remained on the same tyrosine kinase inhibitor (TKI) after locoregional therapy, while 7 were switched to another agent. Of this latter group, four patients were switched to a different TKI, and three were started on a mammalian target of rapamycin (mTOR) inhibitor.

For all patients, the median PFOPOS was 37 months. However, comparing patients who continued the same therapy after locoregional treatment with those who switched, the investigators found a significant survival advantage to sticking with the same therapy, with a median PFOPOS of 39 months, compared with 11 months for patients who were switched to another agent (P = .014)

Other factors contributing to improved survival were good vs. intermediate risk score (39 vs. 29 months; P = .036), metastases to bone vs. viscera (median PFOPOS not reached, vs. 31 months; P = .045), and Fuhrman grade 1 and 2 vs. grade 3 and 4 (57 vs. 37 months; P = .021).

Switching therapies after first progression was an independent risk factor for poor prognosis in a multivariate analysis (hazard ratio 6.280, P = .007).

An analysis of progression-free survival (PFS) after first oligoprogression showed an overall PFS of 14 months. There were no statistically significant differences in terms of post-progression PFS between patients who stayed on the same therapy or were switched, however (15 vs. 7 months, P = .207).

The study was sponsored by participating institutions. The authors reported no conflicts of interest.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

AMSTERDAM – Among patients with advanced renal cell carcinoma (RCC) with metastases to bone, cabozantinib (Cabometyx) was associated with better survival compared with everolimus (Afinitor), according to a subanalysis of data from the METEOR trial.

After 2 years of follow-up, median progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were significantly better for patients with bone metastases who received cabozantinib compared with those who received everolimus, reported Sergio Bracarda, MD, of Presidio Ospedaliero San Donato, Italy, and his colleagues.

“Cabozantinib is a new treatment option for previously-treated patients with advanced RCC with benefits that are maintained in patients with bone metastases,” they wrote in a poster presented at an annual congress sponsored by the European Cancer Organisation.

Previous studies have shown that patients with advanced RCC with bone metastases have generally poor prognosis compared with patients without bone metastases, the authors noted.

As previously reported, the METEOR trial, a randomized phase III study of 658 patients with advanced RCC, showed a significant survival advantage for patients treated with cabozantinib, with a median OS of 21.4 months compared with 16.5 months for patients treated with everolimus, with a hazard ratio (HR) of 0.66 (P = .0003).

In the current sub-analysis, the investigators looked at a subgroup of 142 patients with bone metastases at baseline as seen on CT or MRI. They conducted an exploratory analysis of bone scan response among 162 patients evaluated for bone lesions at baseline by technetium bone scans, and compared the incidence of skeletal-related events (SREs) for 181 patients with a history of SREs, and 477 with no prior SREs. SREs included pathological fractures, spinal cord compression, surgery to bone, and external radiation therapy to bone.

Patients underwent CT or MRI screening every 8 weeks for the first 12 months post randomization, then every 12 weeks thereafter. All patients were screened with technetium bone scans every 18 weeks for the first years, and those patients with bone lesions at baseline were followed with additional scans every 24 weeks.

The authors also looked at serum bone biomarkers, including bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), and C-terminal cross-linked telopeptides of type I collagen.

The median PFS for patients with bone metastases treated with cabozantinib was 7.4 months, compared with 2.7 months for everolimus (HR 0.33, 95% confidence interval [CI] 0.21-0.51). For patients with both bone and visceral metastasis, median PFS was 5.6 months vs. 1.9 months, respectively (HR 0.26, 95% CI, 0.16-0.43).

Median OS for the cabozantinib group was 20.1 months compared with 12.1 months for everolimus (HR 0.54, 95% CI, 0.34-0.84) for patients with bone metastases alone. For patients with both bone and visceral metastases, median OS was 20.1 months with cabozantinib, and 10.7 months with everolimus (HR 0.45, 95% CI, 0.28-0.72).

The ORR with cabozantinib as rated by an independent radiology committee was 17% for patients with bone metastases alone, and 20% for patients with bone and visceral metastases. In contrast, there were no objective responses seen in patients treated with everolimus.

Bone scan responses, defined as a 30% or greater decrease from baseline in bone scan lesion area, were seen in 18% of patients on cabozantinib vs. 10% with everolimus (significance not shown).

Among patients with a history of SREs, 22% had an SRE on cabozantinib, compared with 31% on everolimus. Respective rates among patients without a prior history of SREs were 27% and 15%. At least one SRE occurred in 12% (cabo) and 14% (eve) of patients, including four (cabo) and eight (eve) cases of spinal cord compression. For patients with a history of SREs at randomization, the incidence of postrandomization SREs was 16% (cabo) and 34% (eve) and included zero (cabo) and five (eve) cases of spinal cord compression. Reductions in the bone markers P1NP and CTx were greater with cabo vs. eve. The most common adverse events in patients with bone metastases were consistent with those observed in the overall study population.

The investigators noted that “the safety profile of cabozantinib in the bone metastases subgroup was consistent with the safety profile in the overall population.”

Dr. Bracarda has served as a consultant to Exelixis, which supported the trial and subanalysis. Two coauthors are employees of the company.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.

The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.

decade3d/Thinkstock

Recommendations summarized

The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:

• All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
• For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
• For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
• Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
• Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
• If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m², or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.

The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.

“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.

They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.

The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.

All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.

The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.

decade3d/Thinkstock

Recommendations summarized

The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:

• All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
• For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
• For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
• Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
• Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
• If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m², or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.

The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.

“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.

They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.

The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.

All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.

The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.

decade3d/Thinkstock

Recommendations summarized

The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:

• All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
• For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
• For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
• Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
• Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
• If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m², or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.

The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.

“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.

They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.

The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.