Adjusting for confounding effects of treatment switching in a randomized phase II study of dabrafenib plus trametinib in BRAF V600+ metastatic melanoma

Melanoma Research
Nicholas R LatimerPeng Sun

Abstract

Patients with BRAF V600E mutation-positive melanoma who were assigned to 150 mg dabrafenib twice daily combined with 2 mg trametinib once daily in a phase I/II study showed a median overall survival (OS) of 23.8 months, compared with 20.2 months for patients assigned to dabrafenib alone [hazard ratio (HR)=0.73, 95% confidence interval (CI) 0.43-1.24; data cutoff March 2013], on the basis of an intention-to-treat analysis. Because patients assigned to dabrafenib monotherapy were allowed to switch to combination therapy upon disease progression, we attempted to adjust for confounding effects on OS. Randomization-based adjustment methods, Rank Preserving Structural Failure Time Models and the Iterative Parameter Estimation algorithm, were used. Two analyses, 'treatment group' (assumes that treatment effect continues beyond treatment discontinuation) and 'on treatment' (assumes that the treatment effect disappears upon treatment discontinuation), were used to test assumptions on the durability of the treatment effect. A total of 45/54 (83%) patients assigned to dabrafenib monotherapy switched to the trametinib/dabrafenib combination. Adjusted OS HRs ranged from 0.47 to 0.50, depending on the analysis, compared with the unadjusted O...Continue Reading

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Citations

Mar 22, 2020·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·Thomas R SullivanJonathan Karnon
Feb 25, 2021·Melanoma Research·Ferdy J LejeunePatrick A Riley
Jul 20, 2021·Clinical Lymphoma, Myeloma & Leukemia·Raheel SiddiquiFaiz Anwer

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Clinical Trials Mentioned

NCT01072175

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