Safety and Effectiveness of Lenvatinib in 594 Patients with Unresectable Thyroid Cancer in an All-Case Post-Marketing Observational Study in Japan

Introduction Lenvatinib is approved in Japan for treating patients with all histological subtypes of unresectable thyroid cancer, including differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC). However, safety and effectiveness data are limited in Japanese patients. Therefore, this prospective, post-marketing observational study evaluated, in daily clinical practice, the safety and effectiveness of lenvatinib in Japanese patients with unresectable thyroid cancer. Methods All patients with unresectable thyroid cancer first treated with lenvatinib between May and November 2015 were registered. Patients were orally administered lenvatinib and followed up for 12 months. The endpoints included adverse drug reactions (ADRs), overall survival (OS), overall response rate (ORR), and time-to-treatment failure. Post hoc Cox multivariate analyses were performed to assess prognostic factors associated with the 12-month OS rate. Results Of 629 registered patients, 594 were included in the analysis. A total of 442 patients (74.4%) had DTC, 28 (4.7%) had MTC, and 124 (20.9%) had ATC. Hypertension, proteinuria, and palmar-plantar erythrodysesthesia syndrome were the most frequently reported ADRs across all histological subtypes. The median OS was 101.0 days in patients with ATC which was not reached in patients with DTC and patients with MTC, with 12-month OS rates of 15.6%, 75.7%, and 83.0%, respectively. The ORRs were 59.2%, 45.0%, and 43.8% among 368 patients with DTC, 20 with MTC, and 105 with ATC, respectively. Multivariate analyses revealed that Eastern Cooperative Oncology Group performance status (ECOG PS), tumor size, the presence of tumor invasion, and body weight were baseline prognostic factors affecting OS in patients with DTC, while ECOG PS and the presence of liver metastasis were prognostic factors in patients with ATC. Conclusion Lenvatinib demonstrated an acceptable safety profile for patients with thyroid cancer in a real-world setting in Japan. The safety profile and effectiveness findings for lenvatinib in this study were consistent with those from previous clinical trials, irrespective of histological subtype.