What Survival Benefits are Needed to Make Adjuvant Sorafenib Worthwhile After Resection of Intermediate- or High-Risk Renal Cell Carcinoma? Clinical Investigators’ Preferences in the SORCE Trial

Lawrence, Nicola; Martin, Andrew; Davis, Ian D.; Troon, Simon; Sengupta, Shamik; Hovey, Elizabeth; Coskinas, Xanthi; Kaplan, Richard; Smith, Benjamin; Ritchie, A. W. S.; Meade, Angela; Eisen, Tim; Blinman, Prunella; Stockler, Martin R.

doi:10.3233/kca-180038

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…Further, patients randomised to sorafenib judged larger benefits necessary than those allocated to placebo and clinicians also judged larger benefits necessary. 50 These studies highlight importance of toxicity and quality of life considerations when weighing up benefits and harms of adjuvant treatment.…”

Section: Novel Approaches To Adjuvant Treatment: Tkismentioning

confidence: 99%

<p>Review of Adjuvant Therapies in Renal Cell Carcinoma: Evidence to Date</p>

Tacconi¹,

Tuthill²,

Protheroe³

2020

OTT

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In 2018, there were 400,000 new cases of renal cell carcinoma (RCC) globally, with 175,000 deaths attributable to the disease. Three quarters of patients have potentially curable localised disease at diagnosis; however, recurrence rates are as high as 40% following surgery. There are currently no adjuvant therapies in routine clinical use which reliably improve outcomes. Effective adjuvant therapy is an urgent unmet need to reduce recurrence risk and improve outcomes. Early efforts explored chemotherapy, radiotherapy, cytokine therapy, hormonal treatments and tumour cell vaccines as adjuvant therapies, however, have yielded disappointing results. More recently, interest shifted to evaluating tyrosine kinase inhibitors (TKIs) in the adjuvant setting, as they improve outcomes in metastatic disease. Five phase III clinical trials testing adjuvant use of a range of TKIs have been performed, with the results of a sixth trial awaited. Unfortunately, these studies have thus far yielded conflicting and disappointing results, and there is currently no strong evidence for routine adjuvant TKI therapy. In parallel, novel immunotherapy treatment approaches have recently been developed, transforming the management of a range of malignancies, particularly through immune checkpoint inhibitors (ICIs). These approaches are well established in the metastatic context in RCC, as well as in the adjuvant treatment of melanoma. On this basis, five phase III trials are currently ongoing to test the efficacy of a range of ICIs in adjuvant RCC patients, with initial results expected over the next few years. In this article, we review the current evidence for adjuvant therapies in RCC, discuss ongoing clinical trials and suggest directions for future work to address this unmet need.

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Section: Novel Approaches To Adjuvant Treatment: Tkismentioning

confidence: 99%

<p>Review of Adjuvant Therapies in Renal Cell Carcinoma: Evidence to Date</p>

Tacconi¹,

Tuthill²,

Protheroe³

2020

OTT

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“…Historically, cytokines, known for their limited activity and poor tolerability (8), were the only option available for aRCC. Notably, the management of RCC has been revolutionized in recent years, with the availability of drugs that improve survival for patients with advanced disease dramatically broadening (9,10).…”

Section: Introductionmentioning

confidence: 99%

“…Each of the treatments is associated with different clinical outcomes, administration modes, treatment-related adverse events, and costs (22), so decisions about therapy involve tradeoffs between the possible benefits and harms (9). The European Medicines Agency has indicated that in order to improve the management of treatment toxicities, it is important to better understand the extent to which patients are willing to tolerate AEs and, therefore, the relative importance patients give them (23).…”

Section: Introductionmentioning

confidence: 99%

Preferences for Renal Cell Carcinoma Pharmacological Treatment: A Discrete Choice Experiment in Patients and Oncologists

et al. 2022

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IntroductionThe purpose of this investigation was to explore patients’ and oncologists’ preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC).Material and MethodsCross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference.ResultsA total of 105 patients with aRCC (77.1% male, mean age 65.9 years [SD: 10.4], mean time since RCC diagnosis 6.3 years [SD: 6.1]) and 67 oncologists (52.2% male, mean age 41.9 years [SD: 8.4], mean duration of experience in RCC 10.2 years [SD: 7.5]) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists).ConclusionPatients’ and oncologists’ preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.

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“…Antiangiogenic multi-kinase inhibitors have demonstrated significant efficacy in the metastatic setting, but have not fulfilled expectations in the adjuvant setting. Sorafenib (SORCE trial), pazopanib (PROTECT trial) and axitinib (ATLAS trial) failed to improve disease-free survival when compared with placebo, whereas sunitinib improved disease-free survival but did not impact in overall survival (STRAC trial) [4][5][6][7]. As a consequence, sunitinib has been approved for adjuvant therapy by the Food and Drug Administration, but not by the European Medicines Agency and observation remains the standard of care after resection.…”

Section: Introductionmentioning

confidence: 99%

miRNA profiling in renal carcinoma suggest the existence of a group of pro-angionenic tumors in localized clear cell renal carcinoma

Trilla-Fuertes¹,

Miranda

Castellano

et al. 2020

PLoS ONE

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Renal cell carcinoma comprises a variety of entities, the most common being the clear-cell, papillary and chromophobe subtypes. These subtypes are related to different clinical evolution; however, most therapies have been developed for clear-cell carcinoma and there is not a specific treatment based on different subtypes. In this study, one hundred and sixty-four paraffin samples from primary nephrectomies for localized tumors were analyzed. MiRNAs were isolated and measured by microRNA arrays. Significance Analysis of Microarrays and Consensus Cluster algorithm were used to characterize different renal subtypes. The analyses showed that chromophobe renal tumors are a homogeneous group characterized by an overexpression of miR 1229, miR 10a, miR 182, miR 1208, miR 222, miR 221, miR 891b, miR 629-5p and miR 221-5p. On the other hand, clear cell renal carcinomas presented two different groups inside this histological subtype, with differences in miRNAs that regulate focal adhesion, transcription, apoptosis and angiogenesis processes. Specifically, one of the defined groups had an overexpression of proangiogenic microRNAs miR185, miR126 and miR130a. In conclusion, differences in miRNA expression profiles between histological renal subtypes were established. In addition, clear cell renal carcinomas had different expression of proangiogenic miRNAs. With the emergence of antiangiogenic drugs, these differences could be used as therapeutic targets in the future or as a selection method for tailoring personalized treatments.

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What Survival Benefits are Needed to Make Adjuvant Sorafenib Worthwhile After Resection of Intermediate- or High-Risk Renal Cell Carcinoma? Clinical Investigators’ Preferences in the SORCE Trial

Cited by 5 publications

References 21 publications

<p>Review of Adjuvant Therapies in Renal Cell Carcinoma: Evidence to Date</p>

<p>Review of Adjuvant Therapies in Renal Cell Carcinoma: Evidence to Date</p>

Preferences for Renal Cell Carcinoma Pharmacological Treatment: A Discrete Choice Experiment in Patients and Oncologists

miRNA profiling in renal carcinoma suggest the existence of a group of pro-angionenic tumors in localized clear cell renal carcinoma

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