Original Title: Arzneimittel-Richtlinie/Anlage XII: Cabozantinib (neubewertung nach fristablauf: schilddrüsenkarzinom)

Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.

Authors' results and conclusions: Cabozantinib is indicated for the treatment of adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma. The benefit assessment is based on a re-evaluation of the pivotal study XL184-301 (EXAM), a randomized, double-blinded, multi-center, phase 3 study of cabozantinib (N=219) versus placebo (N=111). No crossover from placebo to active drug was allowed. A median study duration of 500.6 days (min; max: 8; 1808) and 104.0 days (11; 1232) was observed for the intervention and control arm, respectively. Study XL-18-401 (EXAMINER), a randomized, double-blind, multi-center, phase 4 study to evaluate the efficacy, safety and tolerability of two cabozantinib doses (140mg, 60mg), was not part of the benefit assessment because of non-active comparator and non-compliance with 60mg in one arm instead of the approval starting dose of 140mg. The risk of bias for the study XL184-301 and the endpoint overall survival was considered low. No statistical difference in overall survival between both intervention groups was shown in the ITT-population (HR: 0.85 (95%-CI: [0.64; 1.12]); p-value = 0.241) but only in a post-hoc analysis in RET positive subgroup receiving cabozantinib (HR: 0.60 [0.38; 0.94]; p-value = 0.026). However, RET mutation status was unknown for 30% of the patients. For safety parameters, adverse events (AE) occurred more often with cabozantinib than in the control arm: AE CTCAE ≥3 (HR: 2.75 [1.97; 3.83]; p-value

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/710/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-5176/2021-12-16_AM-RL-XII_Cabozantinib_D-698_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/710/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

Organisation Name: The Federal Joint Committee

Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany

Contact Name: Fachberatung Medizin [Department of Medical Consultancy]

Contact Email: Fachberatung-Medizin@g-ba.de

Copyright: https://www.g-ba.de/sys/impressum/