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

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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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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Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15615 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15615-e15615

Author(s):

Ugo De Giorgi ◽

Karim Rihawi ◽

Michele Aieta ◽

Giovanni Lo Re ◽

Teodoro Sava ◽

...

Keyword(s):

Clinical Outcome ◽

Elderly Patients ◽

Renal Cell Cancer ◽

Renal Cell ◽

Performance Status ◽

Cell Cancer ◽

Progression Free Survival ◽

First Line ◽

Metastatic Renal Cell Cancer ◽

Grade 3

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.

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Systemic immune-inflammation index to predict the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.547 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 547-547

Author(s):

Cristian Lolli ◽

Marco Maruzzo ◽

Lisa Derosa ◽

Teodoro Sava ◽

Matteo Santoni ◽

...

Keyword(s):

Renal Cell Cancer ◽

Renal Cell ◽

Cox Regression ◽

Cell Cancer ◽

Progression Free Survival ◽

Bioinformatic Analysis ◽

First Line ◽

Logrank Test ◽

Metastatic Renal Cell Cancer ◽

The Impact

547 Background: A systemic immune-inflammatory index (SII) based on lymphocyte (L), neutrophil (N), and platelet (P) counts has been recently developed. In this retrospective analysis, we explored its prognostic and predictive value at baseline and changes at week 6 during first-line sunitinib in patients (pts) with metastatic renal cell cancer (mRCC). Methods: We included 335 consecutive pts mRCC treated with first-line sunitinib for which P,N, and L data were available at start of therapy, and 6 weeks thereafter. The SII was defined as follows: SII = P x N/L. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the baseline data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion on PFS and OS was evaluated by Cox regression analyses. Results: An optimal cutoff point for the SII of 730 x 109stratified these pts into high (≥ 730) and low SII (<730) groups. Median age was 63 years (range, 27 to 88); histotype clear cell carcinoma was reported in 94% of cases; 29.6%, 59.4% and 11% were classified in the favorable, intermediate and poor Motzer prognostic groups, respectively. The median PFS was 6.2 months (mo) (95% CI=5.5-9.5) in pts with baseline SII ≥730 and 17.7 mo (14.3-21.8) in those with SII <730, P<0.0001. The median OS was 13.7 mo (95% CI=9.6-20.3) in pts with baseline SII ≥730 and 41.8 mo (95% CI=34.5-51.8) in those with baseline SII <730, P<0.0001. Data for SII at baseline and change in SII by week 6 using a cut-off of 730 are shown in the table. Conclusions: The SII is a powerful prognostic and predictive indicator of poor outcome in pts with mRCC. A validation study from prospective data is warranted. [Table: see text]

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275 GATA5 PROMOTER METHYLATION IS ASSOCIATED WITH METASTASIS AND PROGRESSION FREE SURVIVAL IN RENAL CELL CANCER PATIENTS

European Urology Supplements ◽

10.1016/s1569-9056(11)60273-x ◽

2011 ◽

Vol 10 (2) ◽

pp. 106-107 ◽

Cited By ~ 1

Author(s):

I. Peters ◽

H. Eggers ◽

S. Waalkes ◽

J. Hennenlotter ◽

A.S. Merseburger ◽

...

Keyword(s):

Cancer Patients ◽

Renal Cell Cancer ◽

Promoter Methylation ◽

Renal Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

Free Survival

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An individualized dose/schedule strategy for sunitinib in metastatic renal cell cancer (mRCC) on progression-free survival (PFS): Correlation with dynamic microbubble ultrasound (DCE-US) data.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e15149 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e15149-e15149 ◽

Cited By ~ 2

Author(s):

B. Khalil ◽

J. M. Hudson ◽

R. Williams ◽

B. Lloyd ◽

L. M. Milot ◽

...

Keyword(s):

Renal Cell Cancer ◽

Renal Cell ◽

Cell Cancer ◽

Progression Free Survival ◽

Dose Schedule ◽

Free Survival ◽

Schedule Strategy ◽

Metastatic Renal Cell Cancer

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Is there any prognostic importance of pretreatment serum M30 and serum M65 levels on progression-free survival of patients with metastatic renal cell carcinoma treated with first-line sunitinib?

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15569 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15569-e15569

Author(s):

Mert Basaran ◽

Ibrahim Yildiz ◽

Fatma Sen ◽

Leyla Kilic ◽

Serkan Keskin ◽

...

Keyword(s):

Cell Death ◽

Renal Cell ◽

Univariate Analysis ◽

Cell Cancer ◽

Progression Free Survival ◽

Tumor Cell Death ◽

First Line ◽

Free Survival ◽

Median Serum ◽

Metastatic Rcc

e15569 Background: Effective cancer biomarkers for early detection, prognosis, or prediction of therapy response are urgently need in metastatic renal cell cancer (RCC). Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during epitelial cell death. Specific enzyme-linked immunosorbent assays (ELISA) using related antibodies distinguish between apoptotic (M30) or apoptotic and necrotic (M65) tumor cell death in serum samples. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates of patients with metastatic RCC treated with first-line sunitinib. Methods: Thirty-nine patients with metastatic RCC and 39 healthy controls were included in this study. The patients’ samples were collected prior to the first cycle of sunitinib therapy and serum M30 and M65 levels were measured by ELISA. Results: The median ages of the patients and controls were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and controls (53.7 vs. 49.1 U/l, P = 0.31). The median serum M65 level was significantly higher in patients than in controls (334.0 vs. 179.1 U/l, P<0.001). Receiver operating characteristic (ROC) analysis revealed that the best cut-off value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/l. The median PFS of patients whose M65 levels were lower than or equal to 313.6 U/l was better than that of patients whose M65 levels were greater than 313.6 U/l (P = 0.03) in univariate analysis. But serum M65 levels in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions: Serum M65 levels were significantly elevated in patients with metastatic RCC compared to healthy individuals. Future prospective studies with large sample sizes are needed to address the possible impact of M30 and M65 levels on the treatment responses of patients and whether these markers may be prognostic factors for PFS or OS in patients with RCC.

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