How Ponatinib Factors into the Treatment of a Type of Leukemia
Kendra Sweet, MD, discussed results of the the phase 2 OPTIC trial, which investigated ponatinib in a group of patients with resistant, chronic phase chronic myeloid leukemia.
As part of CancerNetwork®’s Face-Off video series, Kendra Sweet, MD, a medical oncologist from the Moffitt Cancer Center, reviewed results from the phase 2 OPTIC trial (NCT02467270).
Transcript:
The OPTIC trial was a study looking at a response-based dose reduction of ponatinib. We know that the prior phase 2 study of the PACE trial (NCT01207440) resulted in excellent responses in a very highly refractory group of patients, however, it also resulted in a high percentage of patients developing arterial occlusive disease. Essentially, the goal of the OPTIC trial was to find the ideal risk-benefit ratio of the drug. Patients were randomized to 3 different doses starting with the plan to dose reduce everyone to 15 mg at the time, that BCR Abl transcripts reach 1% or less. That’s the background of the OPTIC trial.
The update from this year is the 3-year time point of the OPTIC trial. Previously they had reported that the best risk-benefit ratio from that study was found in patients who started at a dose of 45 mg and then dose reduced to 15 mg, BCR Abl transcripts were less than or equal to 1% on the international scale. After 3 years, that still holds true looking at the percentage of patients who achieved material less than or equal to 1%. Then the risk of disease recurrence or essentially rise in BCR Abl transcripts greater than 1%. [In terms of] the dose reduction, what is interesting is that in patients who harbor T315I mutations, the dose reduction down to 15 mg doesn’t seem to be as efficacious, meaning that there are a greater number of patients who lost their response than there were in the group of patients who don't have T315I mutation. Perhaps that’s a group of patients for where we don’t want to be dose reducing all the way down to 15 mg, despite their good responses on a higher dose.
The question still comes, what about the risk of arterial occlusive events, which we’re still seeing, but at much lower rates than what we saw in the PACE trial. In the group of patients starting at 45 mg, we saw 6% of patients with arterial occlusive events. In a group of patients starting at 30 mg was also 6%. In the group of patients at 15 mg, it was 4%, significantly lower than what we saw previously, but still not insignificant. We now have a drug asciminib [Scemblix], which does have activity in the setting of T35I. It’s approved for an arguably equally refractory group of patients, would we want to use ponatinib where there is this risk of cardiovascular toxicity, when we could use asciminib? The counter to that is that nobody has compared asciminib to ponatinib, and we don’t know which one is more effective when comparing the 2 drugs against each other. We have more data in the T35I setting with ponatinib than we do with asciminib. Then again, once we’ve adjudicated the results from the PACE trial, and then looked closely at the data from the OPTIC trial, will cardiovascular events be much slower than they previously were thought to be?
