The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Response-based dosing of ponatinib proved effective in patients with chronic phase chronic myeloid leukemia (CP-CML) who were resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, according to results of the phase 2 OPTIC trial.

The results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Jorge Cortes, MD, of MD Anderson Cancer Center in Houston.

The phase 2 OPTIC trial ( Identifier: NCT02467270) included 283 patients with CP-CML who were resistant or intolerant to at least 2 TKIs or who had the BCR-ABL T315I mutation.

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Patients were randomized to receive different starting doses of ponatinib — 45 mg, 30 mg, and 15 mg. The ponatinib dose was reduced to 15 mg among patients in the 45-mg and 30-mg cohorts who achieved BCR-ABLIS transcript levels of 1% or less.

At baseline, the median age was 46 years in the 45-mg cohort, 51 years in the 30-mg cohort, and 49 years in the 15-mg cohort. More than half of patients in each cohort had received 3 or more prior TKIs, and nearly all patients had stopped their immediate prior TKI due to resistance. Only 1 patient was intolerant to TKIs.

“Patients did have cardiovascular risk factors,” Dr Cortes noted. “More than 25% of the patients had hypertension, 15% to 20% of the patients had hyperlipidemia. There were patients with diabetes [3% to 7%].”

The study’s primary endpoint was reaching BCR-ABLIS transcript levels of 1% or less at 12 months.

The median follow-up was 32 months. The proportion of patients who achieved BCR-ABLIS transcript levels of 1% or less at 12 months was 44.1% in the 45-mg cohort, 29.0% in the 30-mg cohort, and 23.1% in the 15-mg cohort.  

“It is very clear that, with the 45-mg starting dose then reduction to 15 mg, you get the best response rate,” Dr Cortes said.

The higher response rate in the 45-mg cohort was consistent at 6 months, 12 months, and 24 months, despite a median dose intensity of 30 mg, 15 mg, and 15 mg, respectively.

There was no significant difference in progression-free survival (PFS) or overall survival (OS) between the cohorts. The 3-year PFS rate was 73.25% in the 45-mg cohort, 66.33% in the 30-mg cohort, and 69.97% in the 15-mg cohort. The 3-year OS was 89.29%, 88.58%, and 91.71%, respectively.

Treatment emergent adverse events (TEAEs) resulted in treatment discontinuation in 19.1% of patients in the 45-mg cohort, 16.0% in the 30-mg cohort, and 13.8% in the 15-mg cohort. The most common grade 3 or higher TEAEs were thrombocytopenia, neutropenia, and anemia.

“All 3 dosing regimens showed benefit in these largely resistant patients. However, the 45-to-15-mg cohort had the best response,” Dr Cortes concluded. “The responses are durable after dose reduction, and this provides very good overall and progression-free survival.”

Disclosures: This research was supported by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, with additional funding from Incyte Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Cortes JE, Apperley J, Lomaia E, et al. OPTIC primary analysis: A dose-optimization study of 3 starting doses of ponatinib (PON). J Clin Oncol. 2021;39:(suppl 15; abstr 7000). doi:10.1200/JCO.2021.39.15_suppl.7000