Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. (April 2021)

• Record Type: Journal Article
• Authors: Tahara, Makoto; Kiyota, Naomi; Hoff, Ana O.; Badiu, Corin; Owonikoko, Taofeek K.; Dutcus, Corina E.; Suzuki, Takuya; Ren, Min; Wirth, Lori J.
• Is Part Of: European journal of cancer. Volume 147(2021)
• Page Start: 51
• Page End: 57
• Publication Date: 2021-04
• Subjects: Lenvatinib -- Radioiodine-refractory differentiated thyroid cancer -- RR-DTC -- Lung metastases -- Overall survival; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.12.032
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Lung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). Patients and methods: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. Results: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57–1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47–0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1–49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics. Conclusions: Lenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm. Source study registration: ClinicalTrials.Gov Identifier: NCT01321554. Highlights: The survival benefit of LEN was assessed in pts with lung metastases from SELECT. Groups comprised: any lung metastases, ≥1.0 cm, ≥1.5 cm, ≥2.0 cm, or <2.0 cm. OS and PFS: significantly longer with LEN vs placebo in all 4 groups.