Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

Abstract

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC.Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug.Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months.Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

“…EBRT, embolisation, percutaneous treatment modalities) can be done for local control, without discontinuing MKIs [V, C]. Data on real life experiences with lenvatinib in DTC patients are now available and as expected, the drug's efficacy was not as good as that observed in highly selected RCT populations [100,101]. Other antiangiogenic agents have been tested as first-line therapy in phase II trials, with widely varying response rates ( [81,111].…”

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].…”

“…Patients previously treated with an MKI may have different responses than naïve patients and thereby this may impact the results. Kocsis et al [43] ruled out all patients who had been treated with another systematic anticancer treatment, whereas, for example, 62% of the patients included in Balmelli et al [35] had received sorafenib treatment before enrolment.…”

“…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.…”