Lenvatinib Shows Survival Benefit in Radioactive Iodine-Refractory DTC With Lung Lesions

Overall survival (OS) was prolonged in patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) and lung metastases larger than 1 cm who were treated with lenvatinib (Lenvima) compared with placebo, according to results from a post hoc analysis of the phase 3 SELECT study.

Lenvatinib is considered the standard-of-care treatment for locally recurrent or metastatic, progressive RR-DTC, according to the primary analysis of the SELECT study. But based on the shorter survival experienced in patients who also have lung metastases, the SELECT study warranted further exploration of lenvatinib in this subgroup. The post hoc analysis, which was published in the European Journal of Cancer, assessed how the burden of lung metastases impacted survival outcomes in patients with RR-DTC treated with lenvatinib.

The post hoc analysis included patients whose lung lesions were measurable per RECIST v1.1 criteria to be able to evaluate efficacy by lesion size. Looking at patients after they were assigned to either the lenvatinib or placebo arm, 226 and 124 patients, respectively, had a lung metastasis of ≥ 1 cm; 199 and 107 had a lung metastasis of ≥ 1.5 cm; 150 and 84 had a lung metastasis ≥ 2.0 cm; and 94 and 58 had lung metastases < 2.0 cm. Because the post hoc analysis excluded patients without measurable lesions, 27 patients from the lenvatinib arm and 17 from the placebo arm did not undergo further evaluation.

Of the patients included in the lenvatinib arm, 57.3% were younger than 65 years of age and 42.7% were 65 or older. The median height of the arm was 165.1 cm, and the median weight was 72 kg. The majority of patients in the lenvatinib arm had an ECOG performance status of 0 (58.5%), and most of the arm (33.2%) had at least 2 metastatic sites.

Some patients who received lenvatinib in SELECT had other sites of metastasis, including the lymph nodes (51.8%) and the bone (37.2%). The majority of the lenvatinib-treated population did not receive prior VEGF or VEGFR-targeted therapies. In terms of histology, 68.8% of patients had papillary thyroid cancer and 31.2% had follicular thyroid cancer.

In the lung metastasis subgroup, the median OS was 44.7 months in the lenvatinib arm among those with a ≥ 1 cm baseline lung lesion compared with 3.1 months in the placebo arm (HR, 0.63; 95% CI, 0.47-0.85; P = .0025). This population notably was found to have a higher percentage of patients with a baseline ECOG score of 0, which was 58.8% among those in the lenvatinib group compared with 49.5% in the placebo group. Fewer patients had a baseline ECOG score of 1 including 37.2% of the lenvatinib arm compared with 48.6% of the placebo arm.

According to the multivariate analysis, patients who received lenvatinib over placebo had a significant improvement in OS (HR, 0.632; 95% CI, 0.4650-0.858; P = .0033). Contrarily, the subgroup of patients with bone and lymph node metastases did not have a significant improvement in OS. Age was shown to have an impact on OS benefit with lenvatinib. Specifically, patients aged 65 years or younger had a longer OS compared with those above the age of 65 (P = .0243).

Patients with larger lung metastases (2.0 cm) did not experience as much of an OS benefit compared to those with smaller lesions.

Progression-free survival (PFS) was also prolonged in patients with RR-DTC and lung metastases treated with lenvatinib at 20.2 months compared with only 3.7 months in the placebo arm (HR, 0.20; 95% CI, 0.15-0.28; P = .0001). The PFS improvement was significant among patients whose lung metastases were ≥ 1.5 cm, ≥ 2.0 cm, and < 2.0 cm.

The survival benefit of lenvatinib treatment was observed in the study despite the high percentage of crossover from the placebo arm to the lenvatinib arm (89%).

“Despite the high rate of crossover of patients from the placebo arm, significant survival prolongation was observed in the lenvatinib arm among patients with baseline lung metastases of ≥ 1.0 cm. This implies that delaying initiation of lenvatinib treatment may negatively impact a patient’s prognosis,” wrote the study authors, led by Makoto Tahara, MD, of National Cancer Center Hospital East in Japan.

Tahara et al hypothesized that, based on the post hoc analysis results, early initiation of lenvatinib in patients with RR-DTC and lung metastases may improve survival outcomes.

_Reference:

_{Tahara M, Kiyota N, Hoff AO, et al. Impact of lung metastases on overall survival in the phase3 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}