Updated Label for Ponatinib in Resistant Chronic-Phase CML
Posted: Wednesday, December 23, 2020
On December 18, the U.S. Food and Drug Administration (FDA) approved the supplemental new drug application for ponatinib (Iclusig) for adults with chronic-phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors, according to Takeda Pharmaceutical Company. The updated label includes a response-based ponatinib dosing regimen in this patient population, with a daily starting dose of 45 mg and dose reduction to 15 mg once ≤1% BCR-ABL1IS is achieved. This dosing regimen aims to provide efficacy while decreasing the risk of adverse events, including arterial occlusive events.
“The revised indication allows physicians to consider ponatinib earlier in a course of treatment for chronic-phase CML patients, when it might provide the potential for the greatest benefit,” said Jorge E. Cortes, MD, Director of the Georgia Cancer Center, Augusta University, in a press release. (For more from Dr. Cortes on ponatinib, see a recent interview on JNCCN 360.)
The FDA approval is based on 5-year data from the phase II PACE trial as well as the phase II OPTIC trial. The OPTIC trial included patients with chronic-phase CML whose disease was resistant to their immediate prior tyrosine kinase inhibitor. At 12 months, 42% of 88 patients using the newly approved response-based dosing regimen (45 mg to 15 mg) achieved ≤ 1% BCR-ABL1IS, the primary study endpoint, and at a median follow-up of 28.5 months, 73% of these patients maintained their response. In these patients, 13% experienced an arterial occlusive event of any grade (7% were grade 3 or higher). Risk factors such as uncontrolled hypertension or diabetes should be managed, and caution should be exercised when treating patients with an active or substantial history of clinically significant, uncontrolled cardiovascular disease.