Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma

2021 ◽  
pp. 107815522110055
Author(s):  
Ruggero Lasala ◽  
Fiorenzo Santoleri ◽  
Alessia Romagnoli ◽  
Felice Musicco ◽  
Paolo Abrate ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Relevant Literature ◽  
Real Life ◽  
Ecog Performance Status ◽  
Target Therapies ◽  
Baseline Characteristics

Introduction Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. Materials and Methods Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. Results We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS. Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

First-line phase II trial of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma unsuitable for cytokine treatment

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15640-15640 ◽  
Author(s):  
P. Maroto-Rey ◽  
J. Bellmunt ◽  
J. M. Trigo ◽  
V. Guillem ◽  
J. A. López-Martín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Antiangiogenic Agents ◽  
First Line ◽  
Ecog Performance Status ◽  
Cytokine Treatment

15640 Background: Sorafenib (BAY 43–9006) is a serine/threonine and receptor tyrosine kinase inhibitor that prevents tumor cell proliferation and angiogenesis. The objective of this open-label, phase II trial was to determine median progression-free survival (PFS) following sorafenib therapy in patients with renal cell carcinoma (RCC) unsuitable for cytokine treatment. Methods: Eligible patients had cytologically or histologically confirmed clear cell RCC; Eastern Cooperative Oncology Group (ECOG) Performance Status 0–1; adequate renal, liver and medullar function; no active central nervous system metastases; had received no previous treatment with antiangiogenic agents; and had at least one evaluable lesion. Sorafenib was given as first-line treatment in patients unsuitable for cytokine therapy, defined as being intolerant to or ineligible for immunotherapy. Treatment consisted of oral sorafenib 400mg twice daily continuously until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints were response rate according to Response Evaluation Criteria in Solid Tumors, tolerability and overall survival. Results: Twenty-six patients were enrolled between March and July 2006 (median age: 68.5 years [48–82]; male/female: 17/9, ECOG Performance Status 0: 11 patients; prior nephrectomy: 19 patients). The main metastatic locations were lung and bone, 14 patients had = 2 metastatic lesions, and 2 patients had abnormal lactate dehydrogenase levels. As of 31 December 2006, with a median follow-up of 6.4 months, the median PFS had not been reached. In 19 patients evaluable for response, the overall clinical benefit rate was 68.4% (1 complete response; 1 partial response; 11 stable disease). Six patients experienced serious adverse events, only one of which was related to treatment. Conclusions: Sorafenib first-line therapy is a tolerable alternative for patients unsuitable for cytokine treatment. Final PFS data will be available in June 2007. No significant financial relationships to disclose.

Overall and progression-free survival with everolimus, temsirolimus, or sorafenib as second targeted therapies for metastatic renal cell carcinoma: A retrospective U.S. chart review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4612-4612 ◽  
Author(s):  
Hongbo Yang ◽  
Michael K.K. Wong ◽  
James E. Signorovitch ◽  
Xufang Wang ◽  
Zhimei Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Chart Review ◽  
Performance Status ◽  
Progression Free Survival ◽  
Free Survival ◽  
Baseline Characteristics

4612 Background: Tyrosine kinase inhibitors (TKIs) (sorafenib, sunitinib, pazopanib) and inhibitors of the mammalian target of rapamycin (mTORs) (everolimus, temsirolimus) are used for treating metastatic renal cell carcinoma (mRCC) following initial treatment with a TKI. This study’s objective was to establish the effectiveness of the most commonly used 2nd line treatments based on real-use data. Methods: mRCC patients who received a TKI as their 1st targeted therapy and everolimus, temsirolimus or sorafenib as their 2nd therapy were identified by oncologists (85% in community practice) throughout the US as part of an online chart review study. Baseline characteristics were assessed prior to 2nd targeted therapy, including type and duration of initial TKI, response, histological subtype, performance status, and sites of metastasis. Overall survival (OS) and progression free-survival (PFS) were assessed after initiating 2nd targeted therapy. OS and PFS were compared between treatment groups using Cox proportional hazards models adjusted for baseline characteristics. Results: Charts were reviewed for 233, 178, and 123 mRCC patients receiving everolimus, temsirolimus, and sorafenib after an initial TKI, respectively. Median age was 64 years and 70.4% were male. Prior to initiating a 2nd targeted therapy, 86.0% used sunitinib and 85.9% had disease progression. After adjusting for baseline characteristics, everolimus was associated with significantly prolonged OS compared to temsirolimus (hazard ratio [HR] 0.56; CI 0.40-0.78; p<0.001) and sorafenib (HR 0.65; CI 0.42-0.99; p=0.047). Everolimus was associated with significantly longer PFS compared to temsirolimus (HR 0.73; CI 0.55-0.96; p=0.025), and non-statistically significant longer PFS compared to sorafenib (HR 0.75; CI 0.53-1.07; p=0.110). Results were similar in the subgroup with sunitinib as 1st targeted therapy and the subgroup with progression on 1st TKI. Conclusions: Among mRCC patients with prior TKI treatment, everolimus was associated with significantly prolonged OS and PFS compared to temsirolimus and significantly prolonged OS compared to sorafenib.

ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival

2007 ◽  
Vol 43 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Pierre I. Karakiewicz ◽  
Quoc-Dien Trinh ◽  
Alexandre de la Taille ◽  
Claude C. Abbou ◽  
Laurent Salomon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Ecog Performance Status

The role of metastasectomy in patients with renal cell carcinoma with sarcomatoid dedifferentiation: A matched controlled analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 565-565
Author(s):  
Arun Z. Thomas ◽  
Mehrad Adibi ◽  
Rebecca Slack ◽  
Leonardo Daniel Borregales ◽  
Megan M. Merrill ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Surgical Patients ◽  
Ecog Performance Status ◽  
Risk Of Death ◽  
Increased Risk

565 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive tumor generally associated with a poor clinical course. Management of metastatic sRCC remains a therapeutic challenge with no standard treatment strategies. Our objective was to evaluate whether metastasectomy has any survival benefit in patients with synchronous or asynchronous metastatic sRCC treated with radical nephrectomy (RN). Methods: From an institutional database of 273 patients with sRCC treated with nephrectomy, we matched 80 patients with synchronous and asynchronous metastasis for age, ECOG performance status, histology and nodal status. Matched pairs were then retained only if patients who did not undergo metastasectomy were comparably alive at the time of metastasectomy in matched surgical patients to reduce the bias in survival outcomes. Overall survival (OS) from nephrectomy was studied using univariable and multivariable proportional hazards regression. Results: Median OS was 8.3 months (95%CI 6.5-10.5 months) and 18.5 months (95%CI 11.5-42.9 months) for patients with synchronous and asynchronous metastases, respectively. OS for patients undergoing metastasectomy for synchronous metastasis was comparable to non-surgical patients (8.4 and 8.0 months, respectively, p=0.35). Similarly, within the asynchronous cohort, median OS was 36.2 months (95%CI 7.6-Not Reached) in the metastasectomy group and 13.7 months (95%CI 8.8-41.6) in the non-metastasectomy group (p=0.29). On multivariable analysis, positive lymph node (LN) at nephrectomy was associated with increased risk of death in both synchronous and asynchronous patients groups; (HR=2.1 [95%CI 1.1-4.0] p=0.03) and (HR=3.3 [95%CI 1.2-9.2] p=0.02), respectively. Conclusions: Metastasectomy in patients with synchronous or asynchronous metastases after nephrectomy does not appear to confer significant survival benefit in patients with sRCC, particularly in patients with pathological LN positive disease at nephrectomy.

Efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
Ki Hyang Kim ◽  
Sun Young Rha ◽  
Ho Young Kim ◽  
Hye Ryun Kim ◽  
Jong-Mu Sun ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Impairment ◽  
Renal Insufficiency ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Ecog Performance Status

e15573 Background: We investigated the efficacy and toxicity of sunitinib in renal insufficiency patients with metastatic renal cell carcinoma (mRCC). Methods: From Korean Renal Cell Cancer Registry (KRCCR, http://kcsg-rcc.or.kr), we searched renal insufficiency patients with mRCC treated with sunitinib as a first-line treatment between January 2008 and May 2012. The Crockcroft-Gault formula was used for calculation of glomerular filtration rate and selected patients with chronic renal failure not requiring dialysis. Patients characteristics, clinical outcomes, toxicities were evaluated. The patients were divided by 2 groups based on the National Kidney Foundation definition of renal impairment and overall survival (OS) and progression-free survival (PFS) were obtained. Results: From total 997 enrolled from KRCCR, 34 patients were evaluated. Patients characteristics included: median age 66 years, ECOG performance status of 0 and 1 were 90%, and median GFR 46.5 ml/min/1.73m2 (range, 21.1-59.5). The starting dose of sunitinib was 50 mg for 22 patients and 37.5 mg for 12 patients. A schedule of sunitinib was 4 weeks on-2 weeks off for 31 patients, 2 weeks on-2 weeks off for 1 patient and daily for 2 patients. Best response was partial response (N=8) or stable disease (N=12). The median OS and PFS was 26.3 (95% CI: 17.1-35.3) and 12.2 (95% CI: 10.2-13.2) months, respectively. Log rank analysis revealed that severity of renal impairment was significantly associated with PFS but not with OS. Most common adverse events (AEs) of non-hematologic toxicities were stomatitis, rash, general edema and fatigue. The most common grade ≥3 AEs were fatigue, neutropenia and thrombocytopenia. Conclusions: Renal insufficiency patients with metastatic RCC did not impact on the efficacy of sunitinib and did not increased toxicities. Clinicians should not hesitate to treat renal insufficiency patients with metastatic renal cell carcinoma.

Nephrectomy Followed by Interferon Alfa-2b Compared With Interferon Alfa-2b Alone for Metastatic Renal Cell Cancer

2021 ◽  
pp. 113-118
Author(s):  
Christopher Weight
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Interferon Alfa ◽  
Cytoreductive Nephrectomy

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.

Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up.

1993 ◽  
Vol 11 (7) ◽  
pp. 1368-1375 ◽  
Author(s):  
L M Minasian ◽  
R J Motzer ◽  
L Gluck ◽  
M Mazumdar ◽  
V Vlamis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Interferon Alfa ◽  
Advanced Renal Cell Carcinoma ◽  
Survival Duration

PURPOSE Three trials were conducted to define the efficacy and toxicity of interferon alfa-2a in the treatment of metastatic renal cell cancer. Univariate and multivariate analyses were performed to identify prognostic factors for survival. PATIENTS AND METHODS Prospectively, 159 patients were treated with interferon alfa-2a. In the first trial, 42 patients received 50 x 10(6) U/m2 intramuscularly three times per week. In the second trial, 64 patients received gradually escalating doses of interferon alfa-2a from 3 to 36 x 10(6) U subcutaneously administered daily. The third trial was randomized; 25 patients received daily interferon alfa-2a alone and 28 were treated with daily interferon alfa-2a and 0.15 mg/kg vinblastine every 3 weeks. RESULTS The overall response proportion was 10% (two complete and 14 partial responses). The median response duration was 12.2 months. The median survival duration was 11.4 months, with 3% of patients alive at 5 or more years. A univariate statistical analysis showed that a Karnofsky performance status > or = 80, prior nephrectomy, and interval from diagnosis to treatment of longer than 365 days were significant prognostic factors for survival. In a multivariate analysis, only prior nephrectomy and Karnofsky performance status > or = 80 were shown to be independent predictors of survival. CONCLUSION Interferon alfa-2a had minimal antitumor activity in patients with advanced renal cell carcinoma and long-term survival was achieved in a small proportion of patients. The need for continued investigation and the identification of more effective therapy for advanced renal cell carcinoma is evident from the poor overall survival rate observed in these 159 patients. The investigation of new agents and of interferon alfa-2a in combination with other agents remains a priority.

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