An Indirect Treatment Comparison of Cabozantinib Verse Vandetanib in Progressive Medullary Thyroid Cancer (MTC)

  • Rinciog C
  • Myrén K
  • Aldén M
  • et al.
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Abstract

Objectives: MTC is a rare form of thyroid cancer with prevalence of less than 7 per 100,000. A majority of MTC patients have RET mutations, and RET M918T mutations are associated with especially poor prognosis. In 2012, EMA approved the first tyrosine kinase inhibitor (TKI) CAPRELSA(registered trademark) (vandetanib, VDB) for the treatment of MTC. In March 2014, the EMA approved another TKI -COMETRIQ(registered trademark) (cabozantinib, CBZ) for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC, with orphan drug status. The objective of this study was to assess the relative efficacy in PFS and OS of CBZ vs VDB. Methods: Since there are no clinical trials directly comparing the two treatments, an adjusted indirect comparison (Bucher et al. method) was used. Evidence on PFS for the two treatments was collected from the pivotal clinical trials in MTC. The analysis considered all patients and a subgroup of RET M918T mutation positive (RET+) patients. Our analysis focused on PFS due to lack of evidence for the VDB OS in the RET M918T mutation subgroup. In the all patients analysis three different scenarios were explored: a logrank model to ensure comparability with the VDB data; a Cox model stratified on age at randomization and prior TKI status; and a Cox model without stratifications. Results: In the subgroup analysis (logrank model) PFS was estimated to increase by 65% with CBZ comparing to VDB (HR 0.35; 95% CI 0.14-0.87). In the all-patients analysis the estimates were less conclusive: logrank model (HR 0.72; 0.40-1.28), Cox model with stratifications (HR 0.61; 0.35-1.04), Cox model without stratifications (HR 0.66; 0.39-1.13). Conclusions: The results showed a positive trend in favour of CBZ in PFS. Given the limited evidence a direct head-to-head comparison is necessary to validate the study findings.

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Rinciog, C., Myrén, K. J., Aldén, M., Diamantopoulos, A., & LeReun, C. (2014). An Indirect Treatment Comparison of Cabozantinib Verse Vandetanib in Progressive Medullary Thyroid Cancer (MTC). Value in Health, 17(7), A616–A617. https://doi.org/10.1016/j.jval.2014.08.2173

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