Search for Optimal Dose of Ponatinib for Chronic-Phase CML: Update From OPTIC Trial
Posted: Friday, October 23, 2020
Jorge E. Cortes, MD, of the Georgia Cancer Center, Augusta, and colleagues conducted the multicenter phase II OPTIC trial to evaluate the safety and efficacy of the third-generation BCR-ABL1 tyrosine kinase inhibitor ponatinib across three starting doses in patients with chronic-phase chronic myeloid leukemia (CML). The 21-month interim analysis was presented during the virtual edition of the 2020 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract CML-114).
“At this interim analysis, response-based ponatinib dosing regimens resulted in a clinically manageable safety and arterial occlusive event profile,” the investigators remarked. “[An] optimal benefit-risk profile for ponatinib was achieved with a response-adjusted dosing regimen starting with a 45-mg daily dose.”
The study enrolled a total of 283 patients with chronic-phase CML who were resistant or intolerant to at least two prior tyrosine kinase inhibitor therapies or who tested positive for BCR-ABL1 T315I mutation. In a 1:1:1 allocation ratio, they were randomly assigned to receive a starting dose of 45 (cohort A), 30 (cohort B), or 15 (cohort C) mg of oral ponatinib daily. After 12 months, patients in cohorts A and B underwent a mandatory dose reduction to 15 mg daily if they achieved a BCR-ABL1 transcript level of 1% or lower.
Cohort A (38.7%) experienced a higher BCR-ABL1 response rate than cohorts B (27.4%) and C (26.5%). This also seemed to hold true for patients with T315I mutation–positive disease (42%, 24%, and 8%, respectively). Thrombocytopenia was the most frequently reported hematologic adverse event (48.6%). The most common nonhematologic adverse events were hypertension (24.1%) and increased lipase levels (16%). An independent adjudication committee evaluated the arterial occlusive event incidence rates: 5.3% of cohort A; 4.3% of cohort B; and 1.1% of cohort C.
Disclosure: No information regarding conflicts of interest for the study authors was provided.