Real-World Data Reinforces Lenvatinib Use in Differentiated Thyroid Cancer

Thyroid gland: © Anatomy Insider - stock.adobe.com

First-line lenvatinib (Lenvima) continued to demonstrate improved efficacy in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC), according to real-world clinical data gathered from Europe and Canada. These data, presented at the European Society for Medical Oncology Congress 2024, align with results from the phase 3 SELECT trial (NCT01321554) and real-world evidence from the US.¹

“We have included patients from different practice types, including community [17.6%] and academic [75.8%] settings, as well as different countries and regions, representing a highly heterogeneous population,” Laura Deborah Locati, MD, PhD, said in a presentation of the data. Locati is associate professor in the Department of Medical Oncology at the University of Pavia and director of the Translational Oncology Unit at Istituto di Ricovero e Cura a Carattere Scientifico Maugeri in Milan, Italy.

Results and Methodology

In this study, real-world progression-free survival (PFS) was measured from the beginning of lenvatinib treatment until either disease progression or death occurred. If a patient experienced progression, PFS was censored at the start of their next treatment or at the date of their last recorded activity. This applied to real-world overall survival (OS) rates as well.

Laura Locati, MD, PhD

The estimated PFS rates were 78.7% (95% CI, 73.7%-82.9%) at 12 months, 61.5% (95% CI, 54.3%-67.9%) at 24 months, and 53.4% (95% CI, 44.4%-61.5%) at 36 months. At 12 months the estimated OS rates were 92.2% (95% CI, 88.8%-94.7%), 83.1% (95% CI, 78.3%-86.9%) at 24 months, and 77.1% (95% CI, 70.6%-82.4%) at 36 months. The median follow-up period was 17.9 months (interquartile range [IQR], 13.7-22.0). At the end of the follow-up period, 79.8% patients were alive, 18.4% were deceased, and 1.8% were reported as unknown.

Researchers established that 21.1% of patients experienced a complete response and 53.7% had a partial response, resulting in an overall response rate of 74.8%. The estimated PFS rates at 24 months for those experiencing complete response was 95.5% (95% CI, 86.6%-98.5%), and 57.3% (95% CI, 46.7%-66.5%) had partial response. At 24 months the estimated OS rate was not reached (NR; 95% CI, NR-NR) for those who experienced complete response, and 84.4% (95% CI, 77.6%-89.2%) for those with partial response. In addition, 21.4% of patients had stable disease, 3.3% experienced disease progression, and 0.6% were not recorded.

The median duration of treatment was 16.8 months (IQR, 11.1-21.1) and the median follow-up period was 17.9 months (IQR, 13.7-22.0). Lenvatinib was administered once daily at a starting dose of 24 mg for 60.2% of patients, 20 mg for 24.0%, 18 mg for 12.2%, and 14 mg for 3.6%.

“The main goal of this data collection was to assess the clinical effectiveness in real-world data from the patient population of radioiodine-refractory cases from different European countries, the UK, and Canada,” Locati said.

SELECT Trial Results

In the phase 3, randomized, double-blind, multicenter SELECT trial, median PFS was longer in the lenvatinib group at 18.3 months vs 3.6 months in the placebo group (HR, 0.21; 99% CI, 0.14 to 0.31; P =.001).²

The response rate was 64.8% in the lenvatinib group (including 4 complete and 165 partial responses) vs 1.5% in the placebo group (P =.001). The median OS was not reached in either group.

Common treatment-related adverse effects in the lenvatinib group included hypertension (67.8%), diarrhea (59.4%), and fatigue (59.0%). Lenvatinib led to discontinuation in 14.2% of patients vs 2.3% in the placebo group, and 6 out of 20 deaths in the lenvatinib group during the treatment period were drug-related.

Patient Demographics

The retrospective patient chart review included 337 patients with RAI-R DTC who started first-line lenvatinib monotherapy on March 26, 2015, in Europe, or August 9, 2016, in Canada, until January 31, 2022. Lenvatinib was approved in Europe in 2015, and in Canada in 2016.

At lenvatinib initiation, the median age was 60 years (range, 53.0-68.0), 94.7% were White/Caucasian, and 45.1% were women. This review was conducted after an exemption review by the Institutional Review Board.

Regarding clinical characteristics, 60.2% of patients had stage III or IV disease with the following thyroid cancer types: follicular (51.0%), papillary (45.7%), and Hurthle cell (3.3%). In total, 98.8% of patients reported with metastases in various locations: 50.4% in the lymph nodes, 48.1% in the lung, 47.5% in the bone, and 21.2% in the liver.

The majority (67.1%) of patients had an ECOG performance status score of 0 or 1 and 21.1% with 2 or greater. This was a key difference from the SELECT trial which did not include those with a performance status of 2 or greater, Locati noted. Other differences from the SELECT trial included specific criteria for RAI-refractory status, disease progression evidence, and prior treatment with tyrosine kinase inhibitors, the researchers noted.

The study included patients from Canada (16.9%), France (16.3%), Germany (16.6%), Italy (17.8%), Spain (17.5%), and the United Kingdom (14.8%). Data was provided by 91 clinicians who are either medical or clinical oncologists (71.4%) or endocrine oncologists (22.0%).

“We recognize some limitations of this study: the lack of complete safety data, short follow-up period, and real-world variation in clinical outcomes,” Locati concluded.

REFERENCES:

1. Locati L, Gordoa T, Luster M, et al. Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) patients treated with lenvatinib monotherapy: Real-world treatment patterns and clinical outcomes in Europe and Canada. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. Abstract 1926MO

2. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-630. doi:10.1056/NEJMoa1406470