Real-World Retrospective Review Confirms Efficacy of Frontline Lenvatinib Monotherapy in RAI-Refractory DTC

Treatment with lenvatinib (Lenvima) monotherapy induced a complete (CR) or partial response (PR) in 72.4% of patients with radioactive iodine (RAI) therapy-refractory differentiated thyroid cancer (DTC), according to data from a real-world retrospective patient chart review study that was presented at the 91st Annual Meeting of the American Thyroid Association.¹

Moreover, median progression-free survival (PFS) was 49 months and median overall survival (OS) was not reached with lenvatinib.

“Our study reinforces the clinical effectiveness of first-line lenvatinib monotherapy in patients with RAI-[refractory] DTC in real- world clinical practice in the US,” Olivera Rajkovic-Hooley, PhD, Adelphi Real World, Bollington, United Kingdom, and colleagues wrote in the poster presented at the meeting.

Treatment Outcomes and Patterns

The physician-reported best overall response was PR (45.5%), followed by CR (26.9%), and stable disease (18.2%). In addition, 6.5% of patients had progressive disease and 2.9% had an unknown response at the time of evaluation. The median time to best response was 8.6 months (95% CI, 9.4-11.8).

Moreover, median PFS was 49.0 months (95% CI, 37.0-54.2), with estimated 12-, 24-, and 48-month PFS rates of 82.6%, 68.2%, and 54.2%, respectively.

At the end of follow-up, 75% of patients were alive, 23.1% had died, and 1.9% were unknown or lost to follow-up. The median OS was not reached; however, estimated 12-, 24-, and 72-month OS rates were 90.8%, 78.4%, and 57.0%, respectively.

The recommended dose of 24 mg lenvatinib daily was initiated in 62% of patients, while the remaining patients received doses of 14 mg to 20 mg daily. In total, 10.4% of patients required a dose change or interruption during lenvatinib treatment.

At the end of follow-up, 32.1% of patients had discontinued lenvatinib treatment and 67.9% of patients were still on therapy. The median duration of treatment was 17.5 months, with a median of 9.0 months in those who discontinued treatment and 20.2 months in those who were still on therapy. The median time to discontinuation of lenvatinib was 49.0 months (95% CI, 38.5-54.2).

The most common reasons for patients who discontinued treatment (n = 99) were disease progression (36.4%) and death (32.3%). Further, 19 of those who discontinued lenvatinib monotherapy went on to receive second-line treatment, with sorafenib (Nexavar) and cabozantinib (Cabometyx) being the most common types of therapy.

“Results from our real-world retrospective patient chart review study provides evidence on treatment characteristics and related clinical outcomes among patients with RAI-[refractory] DTC treated with first line lenvatinib monotherapy in clinical practice in the US,” Rajkovic-Hooley and colleagues wrote in the poster.

Study Background

In 2015, the FDA approved lenvatinib monotherapy as the first tyrosine kinase inhibitor for the treatment of patients with locally recurrent or metastatic, progressive, RAI-refractory DTC based on efficacy results from the phase 3 SELECT trial (NCT01321554).² Further, 2022 National Comprehensive Cancer Network Guidelines recommended lenvatinib as the preferred agent in RAI-refractory DTC.³

“It is important to understand real-world treatment patterns and related clinical effectiveness of lenvatinib when used in first-line RAI-refractory DTC,” Rajkovic-Hooley and colleagues wrote.

With these advancements, the investigators aimed to assess the patient profiles, real-word treatment patterns, and clinical outcomes of first-line lenvatinib monotherapy in patients with RAI-refractory DTC.

The retrospective patient chart review included 308 patients with RAI-refractory DTC who were treated with frontline lenvatinib monotherapy between February 13, 2015, and September 30, 2020. Data were obtained by prescribing physicians recruited across the US (n = 65), and completed electronic case record forms for patients randomly selected among those meeting the inclusion and exclusion criteria.

Inclusion criteria included a histologically confirmed diagnosis of DTC; a physician-reported diagnosis of RAI-refractory status prior to initiation of lenvatinib monotherapy; ≥18 years of age at the initiation of lenvatinib monotherapy; initiated lenvatinib monotherapy for RAI-refractory DTC in the first-line between February 13, 2015, and September 30, 2020; and completed treatment history that was available from initiation of first-line treatment to last follow-up.

Patients were excluded if they had received lenvatinib for RAI-refractory DTC as part of a clinical trial; had received any systemic treatments for other primary tumors than DTC during the study period; and had synchronous anaplastic histology at diagnosis.

The investigators evaluated for real-world best overall response to lenvatinib, PFS, and OS.

The median age of patients included in the study was 60 years. The majority of patients were female (51.6%), White (73.4%), had either follicular or papillary thyroid cancer (48.4% each), and ECOG performance status of 0/1 (72.4%), and metastases at lenvatinib initiation (89.6%).

Reference:

1. Rajkovic-Hooley O, Zhang J, Reynolds N, Milligan G. Real-world treatment patterns and clinical outcomes in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) patients treated with lenvatinib monotherapy. Thyroid. 2022;32(1):P-1-A-135. doi:10.1089/thy.2022.29137.abstracts.

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- 30. doi:10.1056/NEJMoa1406470.

3. Haddad RI, Bischoff L, Ball D, et al. Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(8):925-951. doi:10.6004/jnccn.2022.0040.