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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma

F Stenner, R Chastonay, H Liewen, SR Haile, R Cathomas, C Rothermundt, RD Siciliano, S Stoll, A Knuth, T Buchler, C Porta, C Renner, and P Samaras.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

This review concluded that first-line treatment with sorafenib followed by treatment with sunitinib was associated with longer progression-free survival in patients with metastatic renal cell carcinoma compared with the same therapies used in reverse order. Some methodological flaws in the review make the reliability of these conclusions unclear.

Authors' objectives

To evaluate the optimal sequence for the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma.

Searching

PubMed, EMBASE and The Cochrane Library were searched for relevant studies to May 2011; search terms were reported. References from seminal articles, reviews and conference abstracts were checked for additional references. Records from patients with metastatic renal cell carcinoma who were treated at five Swiss centres were retrieved.

Study selection

Studies of patients with metastatic renal cell carcinoma who were treated with either sunitinib as first-line therapy followed by sorafenib or sorafenib as first-line therapy followed by sunitinib were eligible for inclusion. Studies were excluded from the review if patients received chemotherapy or anti-angiogenic compounds prior to treatment with tyrosine kinase inhibitors, if treatment discontinuation because of toxicity or intolerance was included in definitions of disease progression and where reasons for discontinuation were not identifiable as progression-free survival.

The patients in the included studies included those in published studies, the authors' caseloads and patients from five Swiss centres. Where stated, median age of the included patients ranged from 57.1 to 64 years and clear cell percentages ranged from 72% to 100%.

The authors did not state how many reviewers performed the study selection.

Assessment of study quality

The authors did not state they assessed quality.

Data extraction

Data were extracted to calculate mean differences (MD) in progression-free survival and 95% confidence intervals (CI) from commencement of both first- and second-line treatment.

The authors did not state how many reviewers performed the data extraction.

Methods of synthesis

Pooled differences in progression-free survival and 95% CI were calculated. Sensitivity analyses were performed after exclusion of studies in which patients had been treated with prior chemotherapy and anti-angiogenic compounds. Regression analyses were performed to examine the impact on the results of clinical factors such as age, gender distribution and study design.

Results of the review

Thirteen studies (853 patients, range nine to 260) were included in the review: two prospective studies, 10 retrospective studies and a retrospective review of the authors' patients. Results from the authors' own caseload were included in the review. Three studies included patients with prior anti-angiotherapy.

A longer period of progression-free survival was observed for patients who were treated with sorafenib as first-line treatment followed by sunitinib than for patients treated with sunitinib as first-line therapy followed by sorafenib (15.4 versus 12.1 months; pooled difference 3.3 months, 95% CI 1.45 to 5.12). There were no significant differences between treatment regimens in the time to disease progression after first-line treatment. For second-line treatment, sunitinib was associated with a longer period of progression-free survival than sorafenib (MD 2.66 months, 95% CI 1.02 to 4.3).

Sensitivity analyses with exclusion of five studies of patients with previous therapy and varying definitions of disease progression showed increases in progression-free survival with sorafenib as first-line treatment compared to sunitinib (MD 3.8 months, 95% CI 2.08 to 5.54). Age, gender and study design were not significantly associated with progression-free survival for any treatment regimen.

Authors' conclusions

Treatment with sorafenib as first-line therapy followed by sunitinib was associated with longer periods of progression-free survival in patients with metastatic renal cell carcinoma than first-line treatment with sunitinib followed by sorafenib as second-line treatment. This effect was driven by a longer second period of progression-free-survival after treatment with sunitinib.

CRD commentary

The review addressed a defined question. Study inclusion criteria were not clear. Appropriate databases were searched for relevant studies and attempts were made to identify unpublished studies. The reviewers stated that patients who received prior anti-angiotherapy were to be excluded from the review but results for these patients from some of the studies were included. There were no reported steps to minimise errors and biases at any stage of the review process and there was no assessment of methodological quality; this made the reliability of the results of the included studies unclear. The included studies were retrospective case series and two prospective cohort studies; results from uncontrolled studies are associated with potential biases so caution is required when interpreting the results. The authors' decision to combine the results from prospective and retrospective studies may not be justified. There were no evaluations of statistical heterogeneity across the studies. Only a few studies were included and they had small sample sizes.

Methodological flaws (including a lack of a robust quality assessment) make the reliability of the authors' conclusions unclear.

Implications of the review for practice and research

Practice: The authors stated that treatment using sorafenib as first-line therapy followed by sunitinib provided benefits in progression-free survival compared to treatment with a single tyrosine kinase inhibitor.

Research: The authors did not state any implications for research.

Funding

No external funding.

Bibliographic details

Stenner F, Chastonay R, Liewen H, Haile SR, Cathomas R, Rothermundt C, Siciliano RD, Stoll S, Knuth A, Buchler T, Porta C, Renner C, Samaras P. A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma. Oncology 2012; 82(6): 333-340. [PubMed: 22677881]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Combined Chemotherapy Protocols /administration & dosage; Benzenesulfonates /administration & dosage; Carcinoma, Renal Cell /drug therapy; Disease-Free Survival; Drug Administration Schedule; Humans; Indoles /administration & dosage; Kidney Neoplasms /drug therapy; Middle Aged; Niacinamide /analogs & derivatives; Phenylurea Compounds; Protein Kinase Inhibitors /administration & dosage; Pyridines /administration & dosage; Pyrroles /administration & dosage; Retrospective Studies; Treatment Outcome

AccessionNumber

12012035663

Database entry date

10/04/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22677881