Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: Does the order of sequencing matter?

Medical Oncology Division and Breast Unit, Sen. Antonio Perrino Hospital, state street 7 to Mesagne, 72100 Brindisi, Italy.
Medical Oncology (Impact Factor: 2.63). 08/2011; 29(3):1908-13. DOI: 10.1007/s12032-011-0048-0
Source: PubMed


To investigate the sequential use of two tyrosine-kinase inhibitors (TKI), sorafenib (SOR) and sunitinib (SUN), in advanced renal carcinoma. We retrospectively analyzed the clinical outcome of 33 patients who had experienced progression or unacceptable toxicity after receiving either sorafenib or sunitinib and then switched to the other reciprocal agent. Progression-free survival (PFS) during the first TKI was similar regardless of drug with a median of 6 months in the SOR-SUN group (n = 15) and 7.5 months in the SUN-SOR group (n = 18). Interestingly, PFS during the second TKI was significantly longer in the SOR-SUN group as compared to the SUN-SOR group with median values of 11 and 3 months, respectively (P = 0.0377; HR 0.46; 95% CI: 0.16-0.95). As a consequence, total PFS (sum of PFS on first and second TKI) was significantly longer in the SOR-SUN group than in the SUN-SOR group with medians of 20 versus 10 months, respectively (P = 0.0393; HR 0.47; 95% CI: 0.18-0.96). Median wash-out period between the two TKI was 3 weeks in both groups. Differences in baseline characteristics, including histology and line of treatment, were not significant, and toxicity was not increased during the second part of the sequence. Here, we show that responses can be achieved when a second TKI is given soon after a TKI failure in renal cancer with apparent more durable disease control when SOR is followed by SUN.

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    • "The results from this study are in line with several previous retrospective studies that have observed a benefit of the sequence sorafenib–sunitinib over sunitinib–sorafenib [7, 12, 15, 16]. None of the prior studies resulted in findings in favor of the sunitinib–sorafenib sequence [7, 11–17]. "
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    ABSTRACT: Sorafenib and sunitinib are used for renal cell carcinoma (RCC). The objective was to study the treatment duration and time to death in Swedish RCC patients on sorafenib or sunitinib as first-line or monotherapy or as sequential therapy. Patients with an RCC diagnosis were identified in the Swedish Cancer Register. Information on treatment with sorafenib and sunitinib was collected from the Swedish Prescribed Drug Register, and time of death from the Cause of Death Register. Outcome measures were duration of treatment and time to death on sorafenib or sunitinib as first-line or monotherapy and sequential therapy (sorafenib–sunitinib versus sunitinib–sorafenib). Poisson regression models were used to estimate hazard ratios (HR) with 95 % confidence intervals (CI). No difference was observed for sorafenib (n = 123 patients) versus sunitinib (n = 261 patients) in treatment duration (HR 1.00; CI 0.80–1.24) or risk for death (HR 1.30; CI 0.91–1.85) when used as first-line or monotherapy. The same applied for sequential therapy with sorafenib–sunitinib (n = 43 patients) versus sunitinib–sorafenib (n = 54 patients), HR 1.47 (CI 0.71–3.02) and HR 2.01 (CI 0.86–4.68), respectively. There was a difference between the two treatments in how the duration of first-line treatment influenced the duration of second-line treatment and time to death, in favor of starting with sorafenib. In conclusion, no difference was detected between sorafenib and sunitinib in the duration of treatment or time to death when used as first-line or monotherapy. The impact of the duration of first-line treatment differed between the two sequences, and the results indicated that sorafenib as first-line treatment is a favorable choice. Electronic supplementary material The online version of this article (doi:10.1007/s12032-012-0331-8) contains supplementary material, which is available to authorized users.
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    ABSTRACT: In metastatic renal cell carcinoma (mRCC), many factors influence clinical decisions, including histology, tumour burden, prognostic factors, comorbidities, and the ability of the patient to tolerate treatment. Progression-free survival (PFS) durations reported from randomized trials of targeted therapies vary considerably, in part because of differences in patient characteristics. For first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus interferon, or sorafenib in a 'general' population is 8-9 months, but each regimen is suitable for different patient categories. For example, sunitinib is suitable for all-prognosis groups, particularly younger, fitter patients; pazopanib for patients with a good or intermediate prognosis; bevacizumab plus interferon for good-prognosis patients or those with indolent disease; and sorafenib for patients at all prognostic risk levels, particularly the elderly and those with comorbidities. Sequential therapy with targeted agents provides significant benefit, and should be considered in all patients who can tolerate such treatment. Level 1 evidence supports sequential use of tyrosine kinase inhibitors, as well as these agents followed by everolimus. We consider how patient characteristics have influenced the results of studies of first-line therapy, and we provide expert opinion on the most appropriate treatment choices for particular patient groups receiving first-line and second-line therapy.
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