Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria

Abstract

Background. Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. Methods. Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39–91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). Results. PFS after 24 months was 71% (95% CI: 56–87), and overall survival (OS) was 74% (95% CI: 60–88), respectively. OS was significantly shorter ( p = 0.048 ) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39–86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66–98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). Conclusion. Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

“…In this selected population, lenvatinib confirmed its efficacy compared to placebo (HR 0.21, 0.08-0.56) [123]. Accordingly, a retrospective multicentric analysis of real-world data confirmed these encouraging results [124]. In this analysis of clinical practice in Austria enrolling 43 patients, the overall survival seemed to be not modified by tumor subtype (differentiated vs. poorly differentiated/anaplastic TC), whereas a maintenance dosage higher than 14 mg was associated with better prognosis [124].…”

“…In this analysis of clinical practice in Austria enrolling 43 patients, the overall survival seemed to be not modified by tumor subtype (differentiated vs. poorly differentiated/anaplastic TC), whereas a maintenance dosage higher than 14 mg was associated with better prognosis [124]. About toxicity, in spite of high proportion of adverse events with grade ≥ III in SELECT trial (75.9%), Austrian, Italian, and French real-world data reported lower rates of adverse events of grade ≥ III (44%, 22.3% and 48%, respectively) [123][124][125][126]. Fatigue, hypertension, diarrhea, decreased weight, stomatitis, and anorexia are the most common reported adverse events [125,126].…”

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

“…Apart from RCTs, several MKIs have also been evaluated in real-world settings in RAIR-DTC [ 83 , 84 , 85 ]. In a retrospective study including 101 patients, lenvatinib and pazopanib displayed comparable efficacy to sorafenib.…”

“…However, serious complications such as hemorrhage, acute coronary syndrome, and thromboembolism occurred more frequently in patients treated with lenvatinib (21%) and pazopanib (13%) compared to sorafenib (7%) [ 83 ]. As doses of 24 mg/day of lenvatinib for the treatment of RAIR-DTC presented with high rates of dose reduction, interruption, and discontinuation [ 85 ], Jiang et al investigated the efficacy of a low-dose lenvatinib (median 10 mg/day). The treatment dose achieved acceptable efficacy and outcomes, with a 48-months PFS of 35.6% (95% CI: 18.5–68.4) and 48-months OS of 54.3% (95% CI: 41.2–71.7).…”

Multimodal Prehabilitation in Radioactive Iodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib.

“…Most common AEs in this latter study were fatigue and hypertension (9). In the RELEVANT study (10), a retrospective multicentric study of real-world data in Austria found that in 43 patients with metastatic RR-DTC, lenvatinib showed sustained clinical e cacy even with reduced maintenance dosages over years (OS 63% with a daily maintenance dosage ≤ 10 mg/day vs. 82% with ≥ 14 mg/day). In this study, Grade ≥3 AEs (hypertension, diarrhea, weight loss, and palmar-plantar erythro-dysesthesia syndrome) were the most common leading to discontinuation of lenvatinib in 16% of the patients.…”