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

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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Re: Validation of Serum Amyloid α as an Independent Biomarker for Progression-Free and Overall Survival in Metastatic Renal Cell Cancer Patients

The Journal of Urology ◽

10.1016/j.juro.2012.11.081 ◽

2013 ◽

Vol 189 (3) ◽

pp. 840-841

Author(s):

M. Pilar Laguna

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Serum Amyloid ◽

Metastatic Renal Cell Cancer

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Sunitinib (2 weeks on/1 week off schedule) in metastatic renal cell cancer patients. Progression free and overall survival

Annals of Oncology ◽

10.1093/annonc/mdw373.47 ◽

2016 ◽

Vol 27 ◽

pp. vi286

Author(s):

F. Gyergyay ◽

B. Budai ◽

K. Nagyivanyi ◽

K. Biró ◽

L. Géczi

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Metastatic Renal Cell Cancer

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Plasma MN (carbonic anhydrase IX) and outcome in sunitinib-treated metastatic renal cell cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.405 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 405-405

Author(s):

Nicholas E. Lamparella ◽

Suhail M. Ali ◽

Kim Leitzel ◽

Walter P. Carney ◽

Allan Lipton

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Carbonic Anhydrase ◽

Cancer Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Carbonic Anhydrase Ix ◽

Lower Plasma ◽

Metastatic Renal Cell Cancer

405 Background: The transmembrane protein MN (carbonic anhydrase IX)(CAIX) catalyzes the hydration of carbon dioxide to carbonic acid and decreases pH. In cancer, up-regulation of CAIX gene expression occurs under hypoxic conditions within tumors. Significant levels of CAIX protein have been detected in a variety of cancers including kidney, cervix, lung, bladder, colon, breast, liver, gall bladder, and pancreas. Methods: Pretreatment plasma CAIX and VEGF-A levels were determined from 52 metastatic renal cell cancer patients enrolled in a phase III first-line trial of sunitinib vs. interferon alpha (IF). The CAIX and VEGF-A ELISAs (WILEX/Oncogene Science, Cambridge MA) were used for determination of plasma biomarker levels. 51 of 52 patients had an MSKCC score of 0 or 1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) plasma CAIX and VEGF levels. Results: Pretreatment plasma CAIX levels averaged 371 pg/ml, with a median of 194 pg/ml and 25th and 75th percentile values of 125 and 298 pg/ml, respectively. In the whole population, higher plasma CAIX was significant on a continuous basis for predicting reduced PFS (p < 0.007) and shorter OS (p <0.0001). When analyzed using the median as cutpoint, the elevated plasma CAIX cohort trended for reduced PFS (p = 0. 13) and had a significantly reduced OS (HR 2.77, p = 0.026) (median 94 vs. 115 weeks). In univariate analysis plasma VEGF-A did not predict for PFS or OS when analyzed as a continuous or dichotomous variable. In multivariate analysis for PFS (including treatment arm, CAIX, and MSKCC score), treatment with sunitinib (vs. IF) (p = 0.006) and lower plasma CAIX (p = 0.04) resulted in a significantly longer PFS. In multivariate analysis for OS, again treatment with sunitinib (vs. IF) (p=0.037), and lower plasma CAIX (p < 0.0001) resulted in a significantly longer OS. Conclusions: Elevated pretreatment plasma CAIX predicted for reduced PFS and overall survival in metastatic renal cancer patients. In addition, sunitinib was superior to interferon, regardless of plasma CAIX status.

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