A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer

Brose, Marcia S.; Panaseykin, Y.; Konda, Bhavana; Fouchardière, Christelle de la; Hughes, Brett; Gianoukakis, Andrew G.; Park, Young Joo; Romanov, I.; Krzyzanowska, Monika K.; Leboulleux, Sophie; Binder, Terri A.; Dutcus, Corina E.; Xie, Ran; Taylor, Matthew H.

doi:10.1210/clinem/dgab731

Cited by 50 publications

(49 citation statements)

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“…Notably, in our cohort, there were more patients with poorly differentiated thyroid carcinoma (22.2%, as compared to 10.7% in SELECT), and the initial dose of lenvatinib was 24 mg daily in only 7 patients (25.9%). Data from a randomized controlled trial by Brose et al showed better ORR with a starting dose of 24 mg compared to 18 mg [ 28 ]. Our population also included 5 patients who had not received any prior radioiodine therapy due to bulky nonoperable primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects

Hamidi

Boucher

Lemieux

et al. 2022

Journal of the Endocrine Society

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Background The SELECT trial led to the approval of Lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse events’ (AEs) profile which may limit its use in clinical practice. We aim to describe the efficacy and toxicity profiles of Lenvatinib in real life. Methods We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% [95% confidence interval (CI), 19.4 to 57.6], and disease control rate was 85.2% [95% CI, 66.3 to 95.8]. The median progression free survival (PFS) was 12 months [95% CI, 7.5 to 16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). 25/27 patients (92.6%) experienced at least one grade ≥ 3 AE, mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, one patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusions Safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report two severe and rarely described AEs that physicians should lookout for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.

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Section: Discussionmentioning

confidence: 99%

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects

Hamidi

Boucher

Lemieux

et al. 2022

Journal of the Endocrine Society

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“…18 mg per day) in a cohort of patients with metastatic/advanced DTC. 5 Not surprisingly, the higher dose turned out to be more effective, in that the objective response rate (ORR) was 57.3% [95% confidence interval (CI) 46.1% to 68.5%] versus 40.3% (95% CI 29.3% to 51.2%) in the lower-dose group [odds ratio 0.50 (95% CI 0.26-0.96)]. The safety profile was comparable.…”

Section: Introductionmentioning

confidence: 96%

ESMO Clinical Practice Guideline update on the use of systemic therapy in advanced thyroid cancer

et al. 2022

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“…A starting dose of lenvatinib 18 mg/day was not noninferior to lenvatinib 24 mg/day, and the safety profile of both starting doses was comparable in highly selected patients within a randomized trial. 28 As such, it is suggested that lenvatinib should be given at the approved starting dose and managed appropriately to avoid prolonged dose interruptions. 29 However, in real-world experience with patients who are not suitable for a trial, have lower body weight, or are elderly, the 24 mg/day starting dose of lenvatinib could lead to toxicity and refusal by patients to resume treatment despite dose modifications.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, clinicians must use their judgement in selecting a starting dose, but their decisions should be informed by the evidence that a 24 mg/day starting dose led to better outcomes in a clinical trial setting. 28 Active monitoring and management of adverse events instituted at drug initiation, and an immediate response by the managing clinician to an adverse event report, may aid in improving patient compliance with treatment. An interesting topic that needs further research is the question of decrease of dosage versus short-term dose interruptions, and which of these strategies could be more beneficial for long-term patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…As such, a multicenter, randomized trial was performed to determine if a lower starting dose of lenvatinib (18 mg/day) could provide noninferior efficacy to the approved 24 mg/day starting dose while having an overall improved safety profile 28 ( Table 1 ). The ORR at week 24 was 57.3% (95% CI 46.1-68.5) in the 24-mg arm versus 40.3% (95% CI 29.3-51.2) in the 18-mg arm (odds ratio 0.50 [95% CI 0.26-0.96]).…”

Section: Reviewmentioning

confidence: 99%

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Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Treatment Optimization for Maximum Clinical Benefit

et al. 2022

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Background Lenvatinib is a multitargeted tyrosine kinase inhibitor approved for treating patients with locally recurrent or metastatic progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC). In this review, we discuss recent developments in the optimization of RR-DTC treatment with lenvatinib. Summary Initiation of lenvatinib treatment before a worsening of Eastern Cooperative Oncology Group performance status and elevated neutrophil-to-lymphocyte ratio could benefit patients with progressive RR-DTC. The median duration of response with lenvatinib was inversely correlated with a smaller tumor burden, and prognosis was significantly worse in patients with a high tumor burden. An 18 mg/day starting dose of lenvatinib was not noninferior to 24 mg/day and had a comparable safety profile. Timely management of adverse events is crucial, as patients with shorter dose interruptions benefitted more from lenvatinib treatment. Caution should be exercised when initiating lenvatinib in patients who have tumor infiltration into the trachea or other organs, or certain histological subtypes of DTC, as these are risk factors for fistula formation or organ perforation. The Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT) eligibility criteria should be considered prior to initiating lenvatinib treatment. Conclusions Current evidence indicates that patients benefit most from lenvatinib treatment that is initiated earlier in advanced disease when the disease burden is low. A starting dose of lenvatinib 24 mg/day, with dose modifications as required, yields better outcomes as compared to 18 mg/day. Appropriate supportive care, including timely identification of adverse events, is essential to manage toxicities associated with lenvatinib, avoid longer dose interruptions, and maximize efficacy.

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A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer

Cited by 50 publications

References 20 publications

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects

ESMO Clinical Practice Guideline update on the use of systemic therapy in advanced thyroid cancer

Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Treatment Optimization for Maximum Clinical Benefit

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