Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients

David J Dorer, Ronalk K. Knickerbocker, Michele Baccarani, Jorge E. Cortes, Andreas Hochhaus, Moshe Talpaz, Frank G. Haluska

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  Ponatinib dose intensity was shown to be associated with rates of adverse events.

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  Pancreatitis, rash, and cardiac failure were most strongly associated with dose.

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  Time-to-event analyses suggest a lag between changes in dose and event risk.

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  No association between dose intensity and venous thromboembolic events was evident.

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  Results support investigating approaches to lower average ponatinib dose intensity.

 The results of these exploratory analyses support the prospective investigation of approaches to lowering the average dose intensity of ponatinib, such as starting at lower doses and/or reducing dose after response, to optimise patient outcomes. Two such studies, both randomised clinical trials, are currently enrolling patients: OPTIC, a phase 2 dose-ranging trial (NCT02467270) in patients with refractory CML to prospectively evaluate the efficacy and safety of 3 starting doses (15 mg/d, 30 mg/d, and 45 mg/d, with reductions to 15 mg/d upon achievement of major cytogenetic response), and OPTIC-2L, a phase 3 comparative trial (NCT02627677) of the efficacy and safety of 2 starting doses of ponatinib (30 mg/d and 15 mg/d) vs. nilotinib (400 mg twice daily) in patients with imatinib-resistant CP-CML.

http://www.lrjournal.com/article/S0145-2126(16)30158-8/fulltext?elsca1=etoc&elsca2=email&elsca3=0145-2126_201609_48__&elsca4=Hematology%7COncology