Renal Cell Carcinoma

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.

Radiofrequency ablation (RFA) of small renal tumors is safe and effective, and is associated with high rates of disease-free survival, according to a study that followed patients for up to 10 years.

In 106 patients who had a total of 112 tumors and who were followed for a median 79 months, 10 recurrences were seen, after an initial procedural success rate of 97%.

Over a 6-year period, Kaplan-Meier disease-free survival (DFS) was 89%, and cancer-specific survival (CSS) was 96%. In the subgroup followed for 10 years, DFS was 82%, CSS was 94%, and overall survival (OS) was 49%.

Tumors were, on average, small (mean 2.5 cm), but for patients whose tumors were larger than 3 cm, the DFS rate fell to 68%. Patients were included in the study if they had a solitary renal mass; those who had metastatic renal cell carcinoma (RCC) or a hereditary kidney cancer syndrome were excluded.

Brett Johnson, MD, and his collaborators from the University of Texas Southwestern, Dallas, noted that an additional 29 patients received RFA but also had partial nephrectomy; these patients were excluded. “Healthier patients with larger tumors may have been advised to undergo partial nephrectomy, thereby selecting for more comorbid patients for RFA,” they noted in discussing their findings. The report was published in The Journal of Urology

Within these parameters, Dr. Johnson and his colleagues conducted a retrospective review of clinic patients whose renal tumors were successfully treated with RFA between the years 2000 and 2007. Patients were followed with yearly imaging, and were considered to have a recurrence if contrast enhancement was seen within the ablation zone at any point after a negative imaging study.

Of the 10 recurrences that were seen, eight were local and two were local and metastatic. An additional patient developed metastatic RCC without evidence of local recurrence; all patients with metastases died of their disease, said Dr. Johnson and his coauthors.

For patients whose tumors recurred, the mean initial tumor size was 3.2 cm, compared with 2.4 cm in those whose tumors didn’t recur (P = .005). Looking at the tumor size data another way, tumor size “was an independent risk factor for cancer recurrence,” with an odds ratio of 3.01 (P = .025), wrote Dr. Johnson and his collaborators.

They noted that it was not routine practice for biopsies to be performed during the initial study period; the seven patients with recurrences who had biopsy data all had clear cell RCC. Median time to local recurrence was 26 months, with no recurrences seen after 5 years.

At the time of the initial procedure, patients were a mean 63.1 years old. The relatively low OS in the subgroup with 10 years of follow-up was likely related to advancing age.

In the subgroup analysis of patients for whom 10-year data were available, the investigators used only data from patients whose initial tumors were biopsied when calculating CSS and metastasis-free survival; these rates were both 94% for those analyzed.

“Age, gender, and time of follow-up had no statistically significant effect on disease-free recurrence” in a univariate analysis, said Dr. Johnson and his colleagues.

“Nephron sparing surgery is the gold standard for treatment of small renal masses,” and the study bolsters the safety and durable efficacy of RFA by using actual survival data rather than actuarial disease survival, said the investigators.

The current study is unique in having such a long duration of follow-up and a subgroup of individuals with 10 years of annual imaging data. In addition, experienced urologists at a single site all used a uniform technique to perform thermal ablation on solitary tumors, noted Dr. Johnson and his coauthors. Successful ablations were followed only by surveillance, in keeping with current American Urological Association recommendations.

However, the study’s retrospective, nonrandomized nature introduces the possibility of selection bias, and variations in follow-up protocols may be a source of ascertainment bias, they said.

The authors reported no conflicts of interest and no outside sources of funding.

SOURCE: Johnson B et al. J Urol. 2018. doi:10.1016/j.juro.2018.08.045.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

SOURCE: AUA Annual Meeting, Abstract PD07-04.

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.

Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.

“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in Clinical Genitourinary Cancer.

The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.

To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.

They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).

They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).

CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).

Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).

The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.

The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.

SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment option for patients with oligometastatic renal cell carcinoma (RCC), according to investigators.

Patients with clear cell RCC who had previously received systemic therapy were more likely to achieve local control, reported Ciro Franzese, MD of Humanitas Clinical and Research Center in Milan, and his coauthors.

These findings contribute to a shifting landscape in RCC; modern techniques are opening doors once closed by disappointing historical results. Several recent SBRT studies have demonstrated local control rates of approximately 90%, compared with conventional RT rates of 20%.

“While the outcomes from conventional RT were quite poor, with SBRT, different biological mechanisms occur due to the use of higher doses per fraction,” the authors wrote in The Journal of Urology.

The present retrospective study involved 58 patients with oligometastatic RCC who were treated with SBRT between 2004 and 2006. Patients previously underwent primary tumor excision, had no greater than three distant extracranial metastases, and were not surgical candidates. Study endpoints included median overall survival (OS), progression-free survival (PFS), and in-field local control (LC). Stratified analysis was also performed in patients with clear cell RCC.

Just over 90% of patients achieved LC at 18 months. Slightly less than half (46.2%) were progression-free at 1 year, and this number dropped to one-third (35%) by 18 months. Median OS was just over 2 years (28 months). Although all patients (100%) were alive at 2 years, this rate dropped to 83% by the 5-year mark.

In patients with clear cell RCC, those treated with systemic therapy prior to SBRT were more likely to achieve LC compared with patients who did not receive systemic therapy (HR 0.15; P = .032).

Overall, SBRT was well tolerated. No grade 3 or higher adverse events occurred. The most common adverse events were pain, fatigue, nausea, and vomiting.

The authors concluded that SBRT is a safe and effective option for patients with oligometastatic RCC. They called for future research to address “the radiobiology of RCC” in order to “understand the role of SBRT and, particularly, its possible interaction with medical therapies.”

The authors reported no conflicts of interest.

SOURCE: Franzese et al. J Urol. 2018 Sep 1. doi: 10.1016/j.juro.2018.08.049.

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment option for patients with oligometastatic renal cell carcinoma (RCC), according to investigators.

Patients with clear cell RCC who had previously received systemic therapy were more likely to achieve local control, reported Ciro Franzese, MD of Humanitas Clinical and Research Center in Milan, and his coauthors.

These findings contribute to a shifting landscape in RCC; modern techniques are opening doors once closed by disappointing historical results. Several recent SBRT studies have demonstrated local control rates of approximately 90%, compared with conventional RT rates of 20%.

“While the outcomes from conventional RT were quite poor, with SBRT, different biological mechanisms occur due to the use of higher doses per fraction,” the authors wrote in The Journal of Urology.

The present retrospective study involved 58 patients with oligometastatic RCC who were treated with SBRT between 2004 and 2006. Patients previously underwent primary tumor excision, had no greater than three distant extracranial metastases, and were not surgical candidates. Study endpoints included median overall survival (OS), progression-free survival (PFS), and in-field local control (LC). Stratified analysis was also performed in patients with clear cell RCC.

Just over 90% of patients achieved LC at 18 months. Slightly less than half (46.2%) were progression-free at 1 year, and this number dropped to one-third (35%) by 18 months. Median OS was just over 2 years (28 months). Although all patients (100%) were alive at 2 years, this rate dropped to 83% by the 5-year mark.

In patients with clear cell RCC, those treated with systemic therapy prior to SBRT were more likely to achieve LC compared with patients who did not receive systemic therapy (HR 0.15; P = .032).

Overall, SBRT was well tolerated. No grade 3 or higher adverse events occurred. The most common adverse events were pain, fatigue, nausea, and vomiting.

The authors concluded that SBRT is a safe and effective option for patients with oligometastatic RCC. They called for future research to address “the radiobiology of RCC” in order to “understand the role of SBRT and, particularly, its possible interaction with medical therapies.”

The authors reported no conflicts of interest.

SOURCE: Franzese et al. J Urol. 2018 Sep 1. doi: 10.1016/j.juro.2018.08.049.

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment option for patients with oligometastatic renal cell carcinoma (RCC), according to investigators.

Patients with clear cell RCC who had previously received systemic therapy were more likely to achieve local control, reported Ciro Franzese, MD of Humanitas Clinical and Research Center in Milan, and his coauthors.

These findings contribute to a shifting landscape in RCC; modern techniques are opening doors once closed by disappointing historical results. Several recent SBRT studies have demonstrated local control rates of approximately 90%, compared with conventional RT rates of 20%.

“While the outcomes from conventional RT were quite poor, with SBRT, different biological mechanisms occur due to the use of higher doses per fraction,” the authors wrote in The Journal of Urology.

The present retrospective study involved 58 patients with oligometastatic RCC who were treated with SBRT between 2004 and 2006. Patients previously underwent primary tumor excision, had no greater than three distant extracranial metastases, and were not surgical candidates. Study endpoints included median overall survival (OS), progression-free survival (PFS), and in-field local control (LC). Stratified analysis was also performed in patients with clear cell RCC.

Just over 90% of patients achieved LC at 18 months. Slightly less than half (46.2%) were progression-free at 1 year, and this number dropped to one-third (35%) by 18 months. Median OS was just over 2 years (28 months). Although all patients (100%) were alive at 2 years, this rate dropped to 83% by the 5-year mark.

In patients with clear cell RCC, those treated with systemic therapy prior to SBRT were more likely to achieve LC compared with patients who did not receive systemic therapy (HR 0.15; P = .032).

Overall, SBRT was well tolerated. No grade 3 or higher adverse events occurred. The most common adverse events were pain, fatigue, nausea, and vomiting.

The authors concluded that SBRT is a safe and effective option for patients with oligometastatic RCC. They called for future research to address “the radiobiology of RCC” in order to “understand the role of SBRT and, particularly, its possible interaction with medical therapies.”

The authors reported no conflicts of interest.

SOURCE: Franzese et al. J Urol. 2018 Sep 1. doi: 10.1016/j.juro.2018.08.049.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The use of tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib to treat metastatic clear cell renal cell carcinoma (RCC) is feasible and effective in Brazil, even though limitations of the public health system mean not all patients have access to these or other therapies, researchers wrote.

In a retrospective analysis of 222 patients with advanced clear cell RCC who were treated with either sunitinib (n = 109) or pazopanib (n = 113), overall survival was 15.2 months with sunitinib and 14.2 months with pazopanib, investigators reported in the Journal of Global Oncology.

Overall survival rates, based on Memorial Sloan Kettering Cancer Center risk categories, were 32.9 months for patients with low risk disease, 15.9 months for intermediate risk patients, and 8.1 months for patient with poor risk – which constituted 29% of the patient population.

Pedro I. Velho, MD, of Johns Hopkins University, Baltimore, and his coauthors noted that these survival rates were lower than those seen in phase 3 trials in the same population.

They suggested this could be caused by the fact that the patients in this real-world study had worse baseline prognoses than those seen in previous clinical trials.

However, they also pointed out that, in the Brazilian public health system, there was no standard systemic treatment option outside clinical trials for patients who have progressed on a TKI as a first-line treatment. Only around half the patients in this study (101) would have been eligible for participation in a clinical trial.

“In our opinion, it is crucial to extend the access to these TKIs for the Brazilian population and also patients in other countries with limited access to targeted therapies,” the authors wrote.

However, the 14 patients who were eligible for treatment with nivolumab under a compassionate use program showed a significantly better overall survival rate, compared with patients who did not have access to a second-line therapy (36.7 months vs. 13.6 months; P less than .001).

“Also, it is imperative to provide systemic sequential treatment options for this population as an attempt to improve survival and offer the best outcomes for patients with metastatic RCC.”

The median duration of treatment with sunitinib was 6.4 months, and with pazopanib, it was 6.7 months. Adverse events were responsible for discontinuation of treatment in 28.4% of patients on sunitinib and 22.1% of patients on pazopanib, with fatigue, diarrhea, nausea and vomiting as the most common toxicities in both groups.

Six authors declared honoraria, funding, expenses or consultancies with the pharmaceutical industry. Two authors had no conflicts of interest to declare.

SOURCE: Velho PI et al. J Glob Oncol. 2018 Sep 10. doi: 10.1200/JGO.18.00073.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.

The combination of a targeted antiangiogenic agent and denosumab (Xgeva) appears to significantly increase the risk for osteonecrosis of the jaw in patients with metastatic renal cell carcinoma (mRCC), French investigators cautioned.

Among 41 patients with RCC metastatic to bone treated with an antiangiogenic agent and denosumab, 7 (17%) developed osteonecrosis of the jaw (ONJ). All seven received the combination in the first line, reported Aline Guillot, MD, from the Institut de cancérologie Lucien Neuwirth in Saint-Priest-en-Jarez, France, and her colleagues.

“The incidence of ONJ was high in this real-life population of patients with mRCC treated with antiangiogenic therapies combined with denosumab. This toxicity signal should warn physicians about this combination in the mRCC population,” they wrote in Clinical Genitourinary Cancer.

Previous studies have shown that the combination of another bone-targeted therapy – zoledronic acid – with antiangiogenic tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent) is associated with increased risk for ONJ. In addition, ONJ with the combination of denosumab and antiangiogenic therapies “has been noticed but never estimated,” the authors noted.

To evaluate the incidence of hypocalcemia and ONJ in patients with RCC metastatic to bone treated with denosumab and a TKI or mammalian target of rapamycin inhibitor, the investigators gathered data retrospectively from 10 French centers.

They identified 25 men and 16 women with a median age of 62 years (range, 54-68 years). Of this group, 40 received denosumab in the first line in combination with either sunitinib (31 patients), pazopanib (6), everolimus (Afinitor and generics; 2), and temsirolimus (Torisel and generics; 1). The median duration of first-line therapy was 12 months.

Denosumab was given in the second line with axitinib (Inlyta) to nine patients, with everolimus to nine, and with sunitinib to three patients. The median duration of second-line therapy was 3 months.

Skeletal-related events occurred in 41% of patients prior to receiving denosumab and in 61% (25 patients) after denosumab. The events included clinical fracture, bone pain requiring radiation, and spinal compression.

Of the seven patients who developed ONJ, six received denosumab and sunitinib in the first line and one received denosumab plus temsirolimus, with a median duration of treatment of 11.8 months. Three of these patients also received denosumab in the second line with either axitinib, everolimus, or sunitinib, with a median duration of 9.8 months. Data on second-line therapy for the remaining four patients with ONJ were not available.

The investigators noted that the 17% incidence of ONJ was higher than the 10% rate seen in a study of patients with mRCC treated with a TKI and a bisphosphonate (Acta Clin Belg. 2018 Apr;73(2):100-9), and the 1.8% incidence seen in an analysis of three phase 3 trials in cancer patients with bone metastases (Ann Oncol. 2012 May;23(5):1341-7).

Although the etiology of ONJ is unknown, patient education and oral hygiene may reduce the risk in patients treated with denosumab and a TKI.

“The benefit of denosumab in this setting in regard [to] toxicity needs to be demonstrated in a prospective trial,” they wrote.

No conflicts of interest or disclosures were reported.

SOURCE: Guillot A et al. Clin Genitourin Cancer. 2018 Sep 6. doi: 10.1016/j.clgc.2018.08.006.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.