Improved Overall Survival Observed With Lenvatinib for Patients With Thyroid Cancer and Lung Metastases

Patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) who had lung metastases of 1 cm or greater experienced improved overall survival (OS) when treated with lenvatinib (Lenvima) compared with placebo, according to data published in the European Journal of Cancer.

These data were taken from the phase 3 SELECT trial (NCT01321554), for which the research team hypothesized that initiating lenvatinib early may improve the outcomes of patients with RR-DTC.² The current analysis looked at patients treated on the trial who had any baseline lung metastases.

“Although OS was not significantly prolonged with lenvatinib treatment versus placebo in patients with any lung metastases, it was significantly prolonged in patients with baseline lung metastases of 1.0 cm [or more],” wrote the investigators. “The results of this analysis also suggest that the treatment effect of lenvatinib may be greater when lenvatinib is initiated in patients with a lower burden of disease, rather than delaying initiation until a higher burden of disease is present.”

The study population included 392 patients with RR-DTC who were randomized 2:1 to receive either lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Patients in the current analysis had any baseline metastases (n = 26) and were further grouped via size of target lung lesions at 1.0 cm or greater (n = 199), 1.5 cm or greater (n = 150), 2.0 cm or greater (n = 94), and more than 2.0 cm (n = 105).

For the group of patients with any lung metastases treated with lenvatinib, there was no statistically significant improvement in OS observed compared with the placebo arm (HR, 0.76; 95% CI, 0.57-1.01; P = .0549).

When analyzing the results by metastases size, a significant improvement in median OS was observed for patients with metastases of 1.0 cm or greater treated with lenvatinib at 44.7 months compared with 33.1 months for patients in the placebo arm (HR, 0.63; 95% CI, 0.47-0.85; P = .0025).

Compared with placebo, prolonged OS for patients treated with lenvatinib were observed in the 1.0 cm or greater (HR, 0.63; 95% CI, 0.47-0.85), 1.5 cm or greater (HR, 0.63; 95% CI, 0.45-0.89), 2.0 cm or greater (HR, 0.65; 95% CI, 0.44-0.98), and less than 2.0 cm (HR, 0.63; 95% CI, 0.40-0.99) patient groups. The median OS reported in the 2.0 cm or greater group (34.7 months) was shorter than that of the other subgroups (range, 44.1-49.2 months).

“In the overall population of patients from SELECT who had any lung metastases, a longer median OS was observed following lenvatinib treatment versus placebo, but the difference was not significant,” wrote the investigators. “…Additionally, lenvatinib treatment resulted in longer OS and PFS in all subgroups, regardless of the size of the lung metastasis at baseline.”

Eligible patients were 18 years or older, had measurable RR-DTC via RECIST v1.1, experienced progression within the last 13 months, had 1 prior VEGF or VEGFR-targeted therapy and had adequately controlled blood pressure.

Patients receiving placebo were allowed to transfer to open-label lenvatinib treatment following disease progression.

References:

1. Tahara M, Kiyota N, Hoff AO, et al. Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer. 2021;147:51-57. doi: 10.1016/j.ejca.2020.12.032

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