Prolonged duration of response in lenvatinib responders with thyroid cancer

Abstract

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2–66.1) was 30.0 months (95% CI 18.4–36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17–0.35; nominal P < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8–44.6) vs 7.9 months (95% CI 5.8–10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders.

Multikinase Inhibitor Treatment in Thyroid Cancer

“…The highest PFS in lenvatinib-treated patients was 33.1 months (95% CI, 27.8-44.6) in Gianoukakis et al [36], which is up to 3 times as high as published in some of the other included studies [32,35]. It is worth noting that Gianoukakis et al [36] was a post hoc analysis focusing only on patients with a response in the SELECT trial [24], thus sorting out the patients with early progression of disease and therefore heightening the PFS compared to other studies.…”

“…Low dose: Hypertension (100%) Proteinuria (83%) Palmar-plantar erythrodysesthesia syndrome (67%) a ≥Grade 3 AE; b marked as severe; c also includes lenvatinib as second-line treatment; d dose reduction because of AEs; e Group 1: duration of dose interruption <10%; f Group 2: duration of dose interruption ≥10%; g treatment-emergent hypertension was an inclusion criterium. N/A: not available For RAI-refractory DTC patients treated with lenvatinib, the PFS varies a lot from the lowest PFS found, 7.2 months [35], to the highest value, 33.1 months [36].…”

“…Dose interruption and reduction harm the long-term efficacy of the drugs [57]. Several of the included studies [35][36][37]40] underlined that early management of the AEs is crucial for the prognosis.…”

Efficacy and tolerability of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer: results of a multicenter observational study in the Russian Federation

“…В исследовании SELECT первичной конечной точкой являлась ВБП, которая рассчитывалась для всех участников независимо от наличия ответа на терапию и составила 18,3 мес по данным основного анализа. Позднее в рамках обновленного анализа [13] медиана Таблица 5. Наиболее частые нежелательные явления, развившиеся на фоне терапии ленватинибом у пациентов с радиойодрезистентным дифференцированным раком щитовидной железы При анализе частоты НЯ у пациентов, участвовавших в нашем исследовании, было установлено, что связанные с лечением НЯ наблюдались почти во всех случаях приема ленватиниба (87 % против 97,3 % в исследовании SELECT).…”

Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis

“…Thus far, 2 multi-targeted tyrosine kinase inhibitors, sorafenib and lenvatinib, have been FDAapproved for the treatment of locally advanced or metastatic progressive RAI-refractory differentiated thyroid cancer. Both had been shown to improve progression-free survival but not overall survival (199)(200)(201). For progressive metastatic MTC, 2 multi-targeted tyrosine kinase inhibitors, vandetanib and cabozantinib showed to improve progression-free survival and have been FDA-approved (202,203).…”