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

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.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MT: Honoraria from Bayer, Bristol Myers Squibb, Eisai, Merck Serono, Takeda; consulting or advisory role with Bayer, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Ono Pharmaceutical, Pfizer; research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Merck Sharp & Dohme, NanoCarrier, Novartis, Ono Pharmaceutical, Pfizer. NK: Honoraria from Ono Pharmaceutical, Bristol Myers Squibb, Merck Serono, AstraZeneca, Eisai, Bayer; research funding from Eisai, AstraZeneca, Pfizer, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb. AOH: Research funding from Eisai, Bayer, Eli Lilly, Exelixis; consulting or advisory role with Bayer, Eli Lilly. CB: Nothing to disclose. TKO: Research funding from Novartis, Astellas, Celgene, Bayer, Stemcentrx, Regeneron, AstraZeneca/MedImmune, AbbVie, G1 Therapeutics, Bristol Myers Squibb, Corvus Pharmaceuticals, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck; consulting or advisory role with Novartis, Celgene, Lilly, Sandoz, AbbVie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol Myers Squibb, MedImmune, BerGenBio, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Heron Pharmaceutical, ARMO BioSciences; IRC/DSMB for EMD Serono, Roche/Genentech; stock ownership with Cambium Oncology. CED: Employee of Eisai Inc. TS: Employee of Eisai Co. Ltd. MR: Employee of Eisai Inc. LW: Consulting or advisory role for Bayer, Blueprint Medicines, Cue Biopharma, Eisai, Exelixis Lilly, Loxo Oncology, Merck, and Rakuten Medical.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)