2805 Overall survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): An updated analysis

Guo, Minggao; Sherman, Steven I.; Wirth, Lorinette S.; Schlumberger, Martin; Dutcus, Corina E.; Robinson, B.; Tahara, Makoto; Latimer, Nicholas

doi:10.1016/s0959-8049(16)31549-0

Cited by 17 publications

(15 citation statements)

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“…In an updated analysis of OS (updated data cutoff 15 June 2014) using a rank-preserving, structural-failure–time model to adjust for crossover, the HR for OS was 0.53; 95% CI: 0.34–0.82, with a nominal bootstrapped P = 0.0051. The median OS for lenvatinib still had not been reached, and was 19.1 months for placebo [12]. …”

Section: Discussionmentioning

confidence: 99%

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes

et al. 2017

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PurposeIn the study of (E7080) lenvatinib in differentiated cancer of the thyroid, most patients experienced an adverse event. In this report, we examine common lenvatinib-emergent adverse events in this phase three, randomized, double-blind study.MethodsAdverse events were graded per Common Terminology Criteria for Adverse Events v4.0. 392 patients were enrolled (lenvatinib: 261, placebo: 131) and received lenvatinib 24 mg/day or placebo. The main outcome measures were: associations with progression-free survival and overall survival in exploratory univariate and multivariate analyses along with additional variables.ResultsThe most common any-grade adverse events (any grade; grade 3) in lenvatinib-treated patients included proteinuria (32%; 10%), diarrhea (67%; 9%), fatigue/asthenia/malaise (67%; 10%), rash (23%; 0.4%), and palmar-plantar erythrodysesthesia syndrome (33%; 3%). There were no grade 4 events for these adverse events. They generally occurred early (median time to first onset [weeks]: proteinuria [6.1], diarrhea [12.1], fatigue/asthenia/malaise [3.0], rash [7.3], and palmar-plantar erythrodysesthesia syndrome [5.9]), and were resolved primarily with dose modifications (median time to resolution [weeks]: proteinuria [8.8], diarrhea [18.1], fatigue/asthenia/malaise [16.3], rash [5.9], and palmar-plantar erythrodysesthesia syndrome [20.0]). Discontinuation due to these adverse events occurred in 2 (1%) patients with proteinuria and 4 (2%) with fatigue. Progression-free survival was not associated with any of the adverse events. Eastern Cooperative Oncology Group performance status (P = 0.001), follicular histology (P = 0.002), and diarrhea (P = 0.023) were associated with overall survival in multivariate analyses (median overall survival for patients with diarrhea: not reached; without: 17.1 months).ConclusionsIn the study of (E7080) lenvatinib in differentiated cancer of the thyroid, the most common adverse events typically occurred early and were primarily managed with dose modifications. Overall survival was significantly associated with diarrhea.

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Section: Discussionmentioning

confidence: 99%

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes

et al. 2017

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“…At the first data cutoff period, OS was not different in patients treated with lenvatinib than in those treated with the placebo, even if a higher rate of response was present in patients treated with lenvatinib, when the potential bias introduced by patient crossover was considered (Schlumberger et al 2015c). More recently, a higher and statistically significant difference in the OS rate using a rank-preserving structural failure time model of patients treated with lenvatinib than in those treated with placebo in the SELECT study was reported at the European Cancer Congress (HR = 0.53; 95% CI: 0.34-0.82, P = 0.0051) (Guo et al 2015). Moreover, when the OS analysis was performed on subgroups of patients, a statistically significant increase of OS was observed in patients > 65 years with respect to younger and in follicular with respect to papillary histotype .…”

Section: :4mentioning

confidence: 99%

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

Viola

Valerio

Molinaro

et al. 2016

Endocrine-Related Cancer

165

130

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Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

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“…The updated results of the SELECT trial were reported at the 2015 European Cancer Congress and they revealed an improvement in overall survival among patients with radioiodine-refractory differentiated thyroid cancer after adjustment by the rank-preserving structural failure time model [41]. Furthermore, an update of the SELECT trial results reported at the 2016 ASCO Annual Meeting indicated that the median progression-free survival and the median duration of response were 19.4 months and 30 months, respectively [42].…”

Section: Hemorrhagementioning

confidence: 99%

Optimal use of lenvatinib in the treatment of advanced thyroid cancer

2017

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The development of orally active, multitargeted kinase inhibitors (MKIs) represents a significant advance in the treatment of progressive, metastatic thyroid cancer. Lenvatinib, an MKI targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and RET, has shown efficacy in stabilizing previously progressive disease, with emerging evidence of a possible benefit in terms of overall survival. However, lenvatinib is associated with a side-effect profile similar to those of other MKIs that might affect the outcome of therapy. The aim of this review is to summarize the clinical efficacy and safety of MKIs in the treatment of advanced thyroid cancer in pivotal phase III trials. Common adverse events that may occur during lenvatinib therapy and their management are discussed, including conditions in which its administration should be temporarily withdrawn and resumed pending resolution of adverse events. We focus on data from a subanalysis of Japanese patients in the SELECT trial and in a post-marketing study in Japan. We suggest that lenvatinib is a valuable treatment option for advanced differentiated thyroid cancer. Monitoring and careful management of adverse events including supportive care are required to ensure continuation of therapy.

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2805 Overall survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): An updated analysis

Cited by 17 publications

References 0 publications

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes

Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

Optimal use of lenvatinib in the treatment of advanced thyroid cancer

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