Does the time before starting first-line treatment influences the survival of patients with metastatic renal cell cancer in favorable-risk groups?

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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Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib

OncoTargets and Therapy ◽

10.2147/ott.s141260 ◽

2017 ◽

Vol Volume 10 ◽

pp. 4885-4893 ◽

Cited By ~ 1

Author(s):

Konstantinos Koutsoukos ◽

Aristotelis Bamias ◽

Kimon Tzannis ◽

Marta Espinosa Montaño ◽

Vasiliki Bozionelou ◽

...

Keyword(s):

Renal Cell Cancer ◽

Real World ◽

Renal Cell ◽

Cell Cancer ◽

Line Treatment ◽

Second Line ◽

Metastatic Renal Cell Cancer

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Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma

Cancers ◽

10.3390/cancers12123750 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3750

Author(s):

Yasir Khan ◽

Timothy D. Slattery ◽

Lisa M. Pickering

Keyword(s):

Renal Cell ◽

Checkpoint Inhibitors ◽

Cell Cancer ◽

Predictive Biomarkers ◽

Therapeutic Options ◽

Current Status ◽

Vegf Receptor ◽

Line Treatment ◽

First Line ◽

First Line Treatment

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.

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Phase II study of individualized sunitinib (SUN) as first-line therapy for metastatic renal cell cancer: Pharmacokinetic data

Annals of Oncology ◽

10.1093/annonc/mdx371.054 ◽

2017 ◽

Vol 28 ◽

pp. v319

Author(s):

G.A. Bjarnason ◽

J. Knox ◽

C.K. Kollmannsberger ◽

D. Soulieres ◽

D.S. Ernst ◽

...

Keyword(s):

Phase Ii ◽

Renal Cell Cancer ◽

Renal Cell ◽

Phase Ii Study ◽

Cell Cancer ◽

Pharmacokinetic Data ◽

First Line ◽

Metastatic Renal Cell Cancer ◽

First Line Therapy ◽

Line Therapy

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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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Phase II study of individualized sunitinib as first-line therapy for metastatic renal cell cancer (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.4555 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 4555-4555 ◽

Cited By ~ 3

Author(s):

Georg A. Bjarnason ◽

Jennifer J. Knox ◽

Christian K. Kollmannsberger ◽

Denis Soulieres ◽

D. Scott Ernst ◽

...

Keyword(s):

Phase Ii ◽

Renal Cell Cancer ◽

Renal Cell ◽

Phase Ii Study ◽

Cell Cancer ◽

First Line ◽

Metastatic Renal Cell Cancer ◽

First Line Therapy ◽

Line Therapy

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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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7107 A randomized, prospective, Phase 2 study, with Sorafenib (So) and Interleukin-2 (IL-2) versus So alone as first line treatment in advanced Renal Cell Cancer (RCC): ROSORC Trial

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)71440-5 ◽

2009 ◽

Vol 7 (2) ◽

pp. 425 ◽

Cited By ~ 3

Author(s):

G. Procopio ◽

E. Verzoni ◽

S. Bracarda ◽

S. Ricci ◽

R. Miceli ◽

...

Keyword(s):

Renal Cell ◽

Cell Cancer ◽

Interleukin 2 ◽

Line Treatment ◽

Phase 2 ◽

First Line ◽

Phase 2 Study ◽

Prospective Phase ◽

Advanced Renal Cell Cancer ◽

First Line Treatment

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Transition to Targeted Therapies Improved the Prognosis and Increased the Utilization of Medical Treatments among Patients with Synchronous Metastatic Renal Cell Cancer

International Journal of Surgical Oncology ◽

10.1155/2021/5237695 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Lauri Laru ◽

Hanna Ronkainen ◽

Markku H. Vaarala

Keyword(s):

Drug Therapy ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Renal Cell Cancer ◽

Targeted Therapies ◽

Renal Cell ◽

Kinase Inhibitors ◽

Cell Cancer ◽

First Line ◽

Metastatic Renal Cell Cancer

Since the introduction of targeted therapies (TTs) for metastatic renal cell cancer (mRCC) in 2005, a limited amount of epidemiological data on efficacy of modern drug therapies for synchronous mRCC has been published. We present a comprehensive nationwide cohort including all cases of primarily metastasized renal cell cancer among adults diagnosed between 2005 and 2010, based on data from the Finnish Cancer Registry and patient records from treating hospitals. Applied treatment protocols and survival outcomes were analyzed. A total of 977 patients were included in the analysis; 499 patients were diagnosed between 2005 and 2007 and 478 patients were diagnosed between 2008 and 2010. The median overall survival (OS) was 8.80 months (95% confidence interval (CI): 7.60–10.02). The median OS of the patients diagnosed at the latter era was significantly better (11.1; 95% CI: 8.8–13.4 vs. 7.0; 95% CI: 5.7–8.3 months, p ≤ 0.001 ). A total number of 524 (53.8%) patients received drug therapy. Altogether, TTs including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTORi), and vascular endothelial growth factor inhibitor covered 331 (63.2%) of first-line treatments, whereas interferon and its combinations with chemotherapy were used for 186 (35.5%) patients. The median OS rates for TT and interferon as first-line therapy groups were 19.9 (16.9–22.8) and 14.9 (12.3–17.4) months, respectively. The OS for patients who did not receive drug therapy after cytoreductive nephrectomy was dismal. We found that the OS estimate of mRCC patients in Finland has improved since the introduction of tyrosine kinase inhibitors. However, the prognosis remains poor for frail, elderly patients with an impaired performance status.

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