Makoto Tahara1, Naomi Kiyota2, Ana O Hoff3, Corin Badiu4, Taofeek K Owonikoko5, Corina E Dutcus6, Takuya Suzuki7, Min Ren6, Lori J Wirth8. 1. National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: matahara@east.ncc.go.jp. 2. Kobe University Hospital Cancer Center, Kobe, Japan. 3. Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. 4. National Institute of Endocrinology, C. Davila University, Bucharest, Romania. 5. Winship Cancer Institute of Emory University, Atlanta, GA, USA. 6. Eisai Inc., Woodcliff Lake, NJ, USA. 7. Eisai Co. Ltd., Tokyo, Japan. 8. Massachusetts General Hospital Cancer Center, Boston, MA, USA.
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 versusplacebo (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.
RCT Entities:
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.
Authors: Anne Christine Kaae; Michael C Kreissl; Marcus Krüger; Manfred Infanger; Daniela Grimm; Markus Wehland Journal: Int J Mol Sci Date: 2021-11-12 Impact factor: 5.923
Authors: Naomi Kiyota; Makoto Tahara; Bruce Robinson; Martin Schlumberger; Steven I Sherman; Sophie Leboulleux; Eun Kyung Lee; Takuya Suzuki; Min Ren; Kazuma Fushimi; Lori J Wirth Journal: Cancer Date: 2022-04-05 Impact factor: 6.921