Two cases of delayed onset of immune‐related adverse events after discontinuation of nivolumab in patients with metastatic renal cell cancer

432 Background: A study was undertaken to investigate the association between treatment with vascular endothelial growth factor (VEGF)-targeted therapy for metastatic renal cell cancer (mRCC) and nephrotoxicity. Methods: Retrospective data were collected for mRCC patients received VEGF-targeted therapy between January 2005 and December 2010. We investigated renal adverse events and clinically significant increased serum creatinine level in patients who received VEGF target therapy. GFR was estimated with the Modification of Diet in Renal Disease (MDRD) formula. Results: Ninety one patients with mRCC who received sunitinib (n=46), sorafenib (n=38), axitnib (n=9) were included in this analysis. As for renal adverse events, acute renal failure occurred in 1 (2.2%) of 46 sunitinib recipients. Facial edema occurred 17 (37.0%) in sunitinib recipients, 2 (5.3%) of sorafenib recipients, 2 (22.2%) of axitinib recipients. In sunitinib recipients, all of these adverse events observed in ‘off’ period. During administration, gradual and significant increase of serum creatinine was observed in sunitinib recipients compared for sorafenib or axitinib recipients (p= 0.04). Significant decrease of GFR compared for baseline correlated with increase of serum creatinine level developed in ‘on’ period of 6 sunitinib administration cycle (p=0.013), but returned to baseline level after 2weeks cessation. No significant change was observed in serum creatinine level and GFR in patients received other VEGF-target agents. Conclusions: Our data suggest that nephrotoxicity developed in a high percentage of patients on sunitinib compared for sorafenib and axitinib in mRCC patients. Clinicians should observe renal function of sunitinib recipients more carefully in ‘off’ period as well as ‘on’ period.

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Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

Future Oncology ◽

10.2217/fon-2020-0900 ◽

2020 ◽

Author(s):

Annemarie Uhlig ◽

Johannes Uhlig ◽

Lutz Trojan ◽

Michael Woike ◽

Marianne Leitsmann ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Skin Reaction ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

Cox Models ◽

Metastatic Renal Cell Cancer ◽

Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

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An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the ‘Pamerit’ study

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa193 ◽

2020 ◽

Author(s):

Alessandra Mosca ◽

Ugo De Giorgi ◽

Giuseppe Procopio ◽

Umberto Basso ◽

Giacomo Cartenì ◽

...

Keyword(s):

Cancer Patients ◽

Renal Cell Cancer ◽

Real World ◽

Renal Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Metastatic Renal Cell Cancer ◽

Metastatic Rcc

Abstract Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P < 0.001), ECOG PS 0 (P < 0.001), age (<75 years, P = 0.005), surgery (P < 0.001) and response to pazopanib (P < 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium’s favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

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