Synergistic Survival: A New Phenomenon Connected to Adverse Events of First-Line Sunitinib Treatment in Advanced Renal Cell Carcinoma

Nagyiványi, Krisztián; Budai, Barna; Bíró, Krisztina; Gyergyay, Fruzsina; Noszek, László; Küronya, Zsófia; Németh, Hajnalka; Gergely, Lajos

doi:10.1016/j.clgc.2015.11.016

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…The conclusion of our previous publication [ 21 ] that patients presenting AEs had longer survival, was also observed in this study: dose reduction, a reflection of AEs, resulted in a longer PFS during the first sunitinib treatment.…”

Section: Discussionsupporting

confidence: 86%

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

et al. 2019

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Background Sunitinib is still one of the standard therapies in metastatic renal cell carcinoma (mRCC). Despite the benefit of sunitinib resistance will develop in the majority of patients. Most of them receive multiple sequential therapies during the course of disease. Objectives To retrospectively investigate the efficacy and safety of rechallenged sunitinib in third or later line settings. Patients and Methods Twenty-one mRCC patients were identified who received rechallenged sunitinib between March 2010 and April 2018. Patients received sunitinib in first or second line, then other tyrosine kinase and/or mTOR inhibitors were applied, then sunitinib was rechallenged. Patients’ characteristics, tolerability, treatment modalities, and treatment outcomes were recorded. The primary end-point was progression-free survival (PFS) of rechallenged sunitinib. Results Median age of patients was 62 years at the start of sunitinib rechallenge. Sixty-seven percent of patients were male. All patients had prior nephrectomy. Upon rechallenge 4 patients achieved partial response and 12 stable disease. The median PFS of first sunitinib treatment was 22 (95% CI 17–26) months and for rechallenged sunitinib 14 (95% CI 6–20) months. No increased severity of prior toxicity or new adverse events was reported during rechallenged sunitinib. The median overall survival (OS) from the start of first sunitinib was 67 (95% CI 46–76) months. Multivariate Cox regression analysis revealed that younger age (< 57 years) at start of first sunitinib (HR = 0.24; 95% CI 0.07–0.79; p = 0.019) and longer (> 2 years) first sunitinib treatment (HR = 0.28; 95% CI 0.09–0.93; p = 0.038) were independent markers of longer OS. Conclusion Sunitinib rechallenge is a feasible and tolerable option with clinical benefit in selected mRCC patients.

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Section: Discussionsupporting

confidence: 86%

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

et al. 2019

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“…Studies 12 demonstrated that mRCC patients with renal impairment (RI) at initial TKI treatment were tended to have a poor prognosis, while others 10 , 13 stated that mRCC patients with RI could equally benefit from TKIs treatment. The development of proteinuria, as well as deterioration of eGFR damage after targeted therapy, was reported to be a predictor for better survival outcomes in patients with TKIs treatment.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Renal Impairment on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors

Zhang

Zhu

et al. 2020

Cancer Control

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Purpose: It remained unclear whether tyrosine kinase inhibitors (TKIs) related renal impairment had impact on the survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinicopathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria and estimated glomerular filtration rate (eGFR) at baseline and during TKIs treatment were recorded. BUN > 7.1mol/L, eGFR <60 ml/min/1.73m2 and/or proteinuria level > 0.3 g/L were defined as renal impairment. eGFR and proteinuria were furtherly classified into different levels. Treatment outcomes were defined as progression-free survival (PFS) and overall survival (OS). Results: At baseline, the presence of abnormal BUN, eGFR and proteinuria level were observed in 25 (22.7%), 27 (25.5%) and 30 (27.3%) patients, which increased to 46 (41.8%), 55 (50.0%) and 64 (58.2%) respectively after TKIs treatment. In the whole cohort (N = 110), survival analysis suggested that only post-treatment renal impairment was related to survival outcomes. Interestingly, sub-analysis showed that post-treatment eGFR level (p = 0.004), proteinuria (p = 0.014) and eGFR decrease >10% (p = 0.012) and elevated proteinuria compared with baseline (p = 0.006) were statistically correlated with OS among patients without RI at baseline (N = 51). On the contrary, deterioration of renal impairment after TKIs treatment in patients with renal impairment at baseline (N = 59) had no relationship with either PFS or OS. Furthermore, eGFR (p = 0.020) and eGFR decrease >10% (p = 0.016) within 1 year after TKIs therapy were potential biomarkers for OS. Conclusion: Dynamic changes of TKI-induced RI during TKIs treatment, especially eGFR and proteinuria level, could be considered as potential biomarkers predicting survival outcomes of mRCC patients.

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“…Improved outcome was presented in our patients with complete or partial tumour response ( p = 0.007). Similarly to other TKI therapies [ 18 – 20 ], the presence of side effects was a strong predictive marker of significantly longer PFS: all side effects ( p = 0.0001), diarrhoea ( p = 0.016). Dose reductions were observed to result in improved PFS (p = 0.016), which also indicates the significance of side effects.…”

Section: Discussionmentioning

confidence: 74%

Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer

Küronya

Szőnyi

Nagyiványi

et al. 2020

Pathol. Oncol. Res.

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Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8-22.4); and 30.2 months (95% CI: 20.3-41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.

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Synergistic Survival: A New Phenomenon Connected to Adverse Events of First-Line Sunitinib Treatment in Advanced Renal Cell Carcinoma

Cited by 11 publications

References 28 publications

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

The Impact of Renal Impairment on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors

Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer

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