scholarly journals Efficacy and Safety of Axitinib as First-Line Therapy in Japanese Patients with Metastatic Renal Cell Carcinoma

2015 ◽  
Vol 06 (08) ◽  
pp. 670-678 ◽  
Author(s):  
Takeshi Namekawa ◽  
Satoshi Fukasawa ◽  
Atsushi Komaru ◽  
Masayuki Kobayashi ◽  
Takayuki Ohzeki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

Comparison of First-line Pazopanib and Sunitinib in Metastatic Renal Cell Carcinoma: Experiences of the Urologic Cancer Centre for Research and Innovation

2019 ◽  
Author(s):  
Emily C.L. Wong ◽  
Camilla Tajzler ◽  
Gaurav Vasisth ◽  
Amanda Zhu ◽  
Mathilda Chow ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Side Effects ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Background: Sunitinib and pazopanib are orally-administered tyrosine kinase receptor inhibitors (TKIs) approved as first-line therapy for the treatment of metastatic renal cell carcinoma (mRCC). The IMDC criteria are a predictive prognostic model for patients with mRCC when stratified into three prognosis groups: favourable, intermediate and poor. We retrospectively compared the efficacy and safety of sunitinib and pazopanib as first-line therapy for patients with mRCC in our single institution database. Methods: Retrospective analysis was done to compare progression-free survival (PFS) and side effects of sunitinib and pazopanib as first-line therapy in patients with mRCC. Patients were stratified into prognosis groups according to IMDC criteria. Disease assessment was performed on measurable aspects of disease based on computed tomography or magnetic resonance imaging reports. Survival analysis was performed using the Kaplan-Meier method and Cox regression, with disease progression as the endpoint.Results: Data was obtained from 228 patients with mRCC who were treated with either pazopanib (n=57) or sunitinib (n=171). No significant difference in PFS was found between sunitinib and pazopanib (HR for disease progression or all-cause death, 1.10; 95%CI: 0.76-1.57, p=0.62). Median PFS time for patients receiving sunitinib was 9.4 months and for pazopanib, 8.5 months. Median PFS for patients with intermediate-risk disease was similar between groups (9.4 months vs. 9.2 months, respectively, p=0.93). However, patients treated with sunitinib experienced a greater number of side effects compared to pazopanib. Conclusions: Sunitinib and pazopanib are similarly efficacious as first-line therapy for mRCC. However, adverse events are lower with pazopanib.

Avoidance of futile treatment and adverse events by using angiogenesis-specific imaging for early detection of disease progression in patients with first-line metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 134-134
Author(s):  
Stephen K. Gruschkus ◽  
Carolyn Bodnar ◽  
Amol Dhamane ◽  
Manan Shah
Keyword(s):  
Renal Cell Carcinoma ◽  
Early Detection ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
First Line ◽  
Early Detection Of Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patients Experience

134 Background: Although sunitinib is effective first-line therapy (1LT) for metastatic renal cell carcinoma (mRCC), ~20% of patients experience rapid progressive disease (PD). Traditional RECIST monitoring often does not detect PD until 90 days after 1LT initiation. Investigational angiogenesis-specific imaging (AI) may identify PD as early as 14 days post-1LT initiation, thus allowing a switch to a potentially more effective second-line therapy and avoiding unnecessary risk of AEs. This study’s goal was to quantify the potential reduction in futile 1LT length, AEs, and costs by using AI for early detection of PD. Methods: Decision modeling with a 90-day horizon evaluated a comparator arm using RECIST monitoring at 90 days and an intervention arm using AI at 14 days. Sunitinib costs were $21,250 for the comparator arm and $13,282 for the intervention arm. RECIST costs were $619 and AI costs were tested as a breakeven analysis. A literature review quantified AE rates associated with 1LT sunitinib and claims data were used to determine costs. Early PD detection was estimated based on a 20% rapid PD rate. Results: For AI sensitivity of 50% to predict rapid PD, a 38-day reduction in futile 1LT could be achieved per PD patient by using AI vs. RECIST (AI sensitivity of 75%/100% yielded 57/76 fewer days). The potential number of AEs avoided through early PD identification is shown below. Costs saved per 1,000 mRCC patients were $684,566 for AEs and $3,187,400 for futile 1LT. Based on these results, $3,872 per mRCC patient would be freed up for AI. Conclusions: Continuing 1LT after PD brings unnecessary risk of AEs and delays potentially effective 2nd-line therapy. Results of this study indicate that early PD identification using AI may improve quality of care by minimizing duration of futile 1LT and avoiding unnecessary AEs. [Table: see text]

Clinical and prognostic implications of delta-like ligand 4 and hypoxia-inducible factors in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib as first-line therapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Mian Xie ◽  
Chao sheng He ◽  
Zhao hui He ◽  
Qi zhan Lin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Treatment Schedule ◽  
Prognostic Impact ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Prognostic Implications

e15567 Background: Sunitinib is recommended as the first line treatment of patients with metastatic renal cell carcinoma (mRCC). Delta-like ligand 4 (DLL4) is a Notch ligand that is upregulated by hypoxia and has a role in tumor angiogenesis. The aim of this study was to evaluate clinical and prognostic implications of DLL4 and markers of hypoxia in mRCC patients treated with sunitinib as first-line therapy. Methods: Treated-naïve, clear cell mRCC patients were received sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2). We prospectively collected plasma samples before treatment and the expressions of DLL4, Notch1, HIF-1α, HIF-2α were measured using enzyme-linked immunosorbent (ELISA). Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. The log-rank test was used to assess the significance of univariate survival analysis. Multivariate analysis using Cox Regression model was performed to identify independent prognostic factors. Results: Between Aug 2008 and Sep 2010, consecutive 86 patients with mRCC were enrolled. Median follow up period was 35 months. The objective response rate (ORR) was 29.3% (95% confidence interval [CI], 13.5% to 37.7%), median PFS was 10.1 months (95% CI, 8.7 to 12.1 months), and median OS was 23.6 months (95% CI, 16.8 to 26.5 months). Most treatment-related side effect were mild to moderate, including hypertension, fatigue, thrombocytopenia and hand-foot syndrome. Both high DLL4 and low HIF-1α levels significantly correlated with lower ORR (DLL4: 19.8% versus 31.7%, P < 0.001; HIF-1α: 16.8% versus 33.5%, P = 0.002) and shorter PFS (DLL4: 8.6 versus 12.1 months, P = 0.01; HIF-1α: 8.3 versus 11.9 months, P = 0.01), but this was not predictive of OS. Neither survival nor ORR was associated with expressions of Notch1 and HIF-2α. Conclusions: Sunitinib has shown effective anti-tumor activity in treatment-naïve mRCC patients. High expression of DLL4 and low expression of HIF-1α may mediate resistance to sunitinib. Baseline levels of DLL4 and HIF-1α have prognostic impact on PFS for patients treated with sunitinib.

Improvement of Medical Treatment in Japanese Patients With Metastatic Renal Cell Carcinoma

2022 ◽  
Vol 2 (1) ◽  
pp. 25-30
Author(s):  
RYO FUJIWARA ◽  
YOSHINOBU KOMAI ◽  
TOMOHIKO OGUCHI ◽  
NOBORU NUMAO ◽  
SHINYA YAMAMOTO ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Treatment Period ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clinical Factors ◽  
First Line ◽  
Factors Associated ◽  
First Line Therapy ◽  
Line Therapy

Background/Aim: To evaluate the relationship between treatment period and overall survival (OS) and to identify clinical factors associated with OS in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Two hundred thirteen consecutive patients with mRCC receiving systemic therapy between 2008 and 2020 were divided into two groups: those starting first-line therapy in 2008-2015 (n=133) and those in 2016-2020 (n=80). Clinical factors associated with OS were retrospectively and statistically analyzed. Results: Median OS and one-, three- and five-year OS rates were not reached and 88.7%, 64.9%, and 64.9% in patients treated in 2016-2020; 31.4 months and 78.5%, 42.8% and 34.2% in 2008-2015 (p=0.0013). Multivariate analysis identified the period in which first-line therapy was started as the strongest predictor for OS (p=0.0002). Conclusion: OS was significantly better in mRCC patients treated in 2016-2020 than in 2008-2015. Treatment period was the strongest predictor for OS.

Combination of immunotherapy and tyrosine kinase inhibitor in first-line metastatic renal cell carcinoma: A real-world Indian experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16576-e16576
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
Nitin Yashas Murthy ◽  
SP Somashekhar ◽  
Shabber Zaveri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

e16576 Background: Immuno-oncology (IO) agents in combination with oral tyrosine kinase inhibitors (TKIs) has become a standard first line therapy in metastatic renal cell carcinoma (mRCC) patients. Various combinations such as pembrolizumab + axitinib, avelumab + axitinib, nivolumab + cabozantinib and pembrolizumab + lenvatinib have all shown better results than sunitinib. There is very limited data about this from India. Methods: This is a single center, retrospective study of mRCC patients, who received first line treatment was nivolumab or pembrolizumab with axitinib or lenvatinib. The endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AE). Results: Between Jan 2019 to Jan 2021, 22 patients were treated with IO + TKI combination. 12 patients received axitinib, and 10 lenvatinib. Age range was 35 to 78 years with 18 males and 4 females. IMDC risk stratification showed 3 favorable (13.6%), 13 intermediate (59%) and 6 poor risk (27.2%) patients. 2 patients (9%) achieved complete response(CR), 13 (59%) partial response (PR), 4 (18.2%) had stable disease and 3 (13.6%) progressed. The ORR was 68%. Median PFS was 22 months (1 month- 24 months). OS at 1 year was 92%, and median OS was not reached. Grade 3/4 immune related adverse events (AEs) were seen in 3 (14.2%) patients (1 colitis,1 pneumonitis,1 encephalitis), for whom the IO was discontinued. TKI related grade 3/4 AEs were seen in 8 patients (38%), and were managed with dose reductions. Conclusions: Combination IO + TKI is a very effective first line therapy in mRCC. An ORR of 68%, median PFS of 22 months and 1 year OS of 92% is the best we have seen in our patients. The efficacy of this combination is seen in all IMDC subgroups. The combination is well tolerated, and the TKI AEs are comfortably managed with dose reduction. IO combinations should be preferred over single agent TKIs (sunitinib or pazopanib) as first line therapy.

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