Background Lenvatinib is a multikinase inhibitor approved to treat radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day. This study explored, in a double-blinded fashion, whether a starting dose of 18 mg/day would provide comparable efficacy with reduced toxicity. Methods Patients with RR-DTC were randomized to lenvatinib 24 mg/day or 18 mg/day. The primary efficacy endpoint was objective response rate as of Week 24 (ORRwk24); odds ratio noninferiority margin: 0.4. The primary safety endpoint was frequency of grade ≥3 treatment-emergent adverse events (TEAEs) as of Week 24. Tumors were assessed using RECIST v1.1. TEAEs were monitored and recorded. Results The ORRwk24 was 57.3% (95% confidence interval [CI] 46.1–68.5) in the lenvatinib 24-mg arm and 40.3% (95% CI 29.3–51.2) in the lenvatinib 18-mg arm, with an odds ratio [18/24 mg] of 0.50 (95% CI 0.26–0.96). As of Week 24, the rates of TEAEs grade ≥3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, a difference of −4.2% (95% CI −19.8–11.4). Conclusion A starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared with a starting dose of 24 mg/day as assessed by ORRwk24 in patients with RR-DTC. The results represent a clinically meaningful difference in ORRwk24. The safety profile was comparable, with no clinically relevant difference between arms. These results support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC and adjusting the dose as necessary.

A multicenter, randomized, double-blind, phase II study of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) to evaluate the safety and efficacy of a daily oral starting dose of 18 mg vs 24 mg

Background: In the phase 2 double-blind Study 211, a starting dose of lenvatinib 18 mg/day was compared with the approved starting dose of 24 mg/day in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Predefined criteria for noninferiority for efficacy in the 18 mg arm were not met; safety was similar in both arms. Impact of lenvatinib treatment on health-related quality-oflife (HRQoL) was a secondary endpoint of Study 211.

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Despite recent advances in radiation therapy, osteoradionecrosis remains a common and severe complication of radiation therapy in patients with head and neck cancer. Modern methods of treatment are developed with regard to the disease severity and pathophysiology complexity, as well as theories of the osteoradionecrosis development. The following theories of osteoradionecrosis pathophysiology are currently considered: "radiation-induced osteomyelitis", "hypoxic, hypocellular, hypovascular" and "fibroatrophic". Prior to radiation therapy, the patient is provided with restorative dental treatment and radiation therapy planning. Treatments range from conservative «watch and wait» to more radical surgical interventions. Currently, there is no approved standard for the care of osteoradionecrosis patients, however, the activity in this direction is underway. Currently state-of-the-art treatment strategies are available with limited evidence. The review aims to assess the literature on osteoradionecrosis of the jaw with an emphasis on available treatment options.