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OS similar among mRCC patients enrolled in clinical trials across different geographic regions
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.
Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.
“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”
This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.
SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
FROM journal of global oncology
Key clinical point: The potential differences in clinical outcomes may be contributed by differences in access to clinical trials, disease biology, reporting of adverse events, and quality of care.
Major finding: Patient characteristics differed according to geographic region. No statistically significant differences in OS were observed when the United States/Canada (USC) was compared with other regions: Latin America, Asia/Oceania/Africa, and Eastern Europe.
Study details: Pooled retrospective analysis of 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.
Disclosures: The study was funded by Pfizer and in part by the Dana Farber/Harvard Cancer Center. All of the study authors reported conflicts of interest involving the sponsor, Pfizer, or other pharmaceutical companies.
Source: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.
Refractory FGFR-altered cholangiocarcinoma responds to FGFR kinase inhibitor
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
BGJ398, a first-in class pan–fibroblast growth factor receptor (pan-FGFR) kinase inhibitor, had modest clinical activity and a manageable toxicity profile, according to results of a phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
FGFR-2 fusion mutations are found in 13% to 17% of patients with intrahepatic cholangiocarcinoma, a rare and highly aggressive cancer. Cholangiocarcinomas have a poor prognosis and are often diagnosed at an advanced unresectable stage with limited options after disease progression on gemcitabine-based therapy.
In the multicenter, open-label, single-arm study, single agent BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions. The disease control rate (complete response plus partial response plus stable disease rate) was 75.4% with a median progression-free survival of 5.8 months, Milind Javle, MD, and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, wrote in the Journal of Clinical Oncology (2017. doi: 10.1200/JCO.2017.75.5009).
BGJ398 was given orally once daily at a dose of 125 mg for 21 days followed by 7 days off the drug as part of a 28 day cycle that was based on findings from a phase 1 study. However, primarily because of treatment-related adverse events, 77% of patients required dose interruptions, and 62.3% required a median of two dose reductions to achieve a median drug exposure of about 4.7 months.
The most common all-grade treatment-related adverse event reported was hyperphosphatemia (72.1%), followed by fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Other toxicities, such as dry eyes (21.3%), blurred vision (14.8%), and onychomadesis (18%) were also reported. Serious adverse events (grade 3 or 4) were reported in 41% of patients, and 8.2% of patients discontinued treatment due to adverse events.
The toxicity profile was predictable, however, and was alleviated by intermittent (3-weeks-on/1-week-off) dosing, prophylaxis using phosphate-lowering agents, and dose reductions.
Although 100% of patients enrolled eventually acquired resistance to BGJ398 and experienced disease progression, a median progression-free survival of 5.8 months is encouraging, and this targeted therapy warrants further clinical evaluation, the authors concluded.
The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the study authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: of 61 patients with chemotherapy refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
Major finding: BGJ398 was associated with an overall response rate of 14.8% in 61 patients with predominant FGFR-2 fusions.
Data source: A phase 2 study of 61 patients with chemotherapy-refractory, advanced or metastatic cholangiocarcinoma with alterations in genes encoding FGFR.
Disclosures: The study was funded by Novartis Pharmaceuticals. Dr. Javle and two other authors reported having no disclosures. Four of the authors are Novartis employees, and several other authors reported conflicts of interest involving the sponsor or other pharmaceutical companies.