How ODAC Decisions on PI3K Inhibitors Impact CLL/SLL Treatment

Cyrus M. Khan, MD, a hematologist at the Allegheny Health Network Cancer Institute, discusses how decisions made by the FDA’s Oncologic Drug Advisory Committee (ODAC) has impacted treatment decisions for physicians treating patients with chronic lymphocytic leukemia (CLL) and studying the use of PI3K inhibitors for these patients.

In 2022, ODAC voted 16 to 0 that any future approvals of a PI3K inhibitor for patients with CLL has to be supported by randomized data despite observed toxicities in this drug class, research showing a detriment in overall survival, and a narrow range between effective and toxic doses. According to Khan, while there have been setbacks with the use of these drugs this has made sure that any future studies must have a stronger support for OS when using a PI3K inhibitor.

Further, in 2022, ODAC also voted 8 to 4 that the benefit/risk profile of the PI3K inhibitor duvelisib (Copiktra) was unfavorable for patients with relapsed or refractory CLLor small lymphocytic lymphoma (SLL) who had at least 2 prior therapies. The committee was impressed with the progression-free survival (PFS) data with the drug which showed an extended PFS for patients with high-risk chromosome 17p13.1 deletions and/or TP53 mutations in their disease compared to ofatumumab (HR = 0.52; P < .0001). Moreover, the median PFS with duvelisib for patients in phase 3 DUO trial (NCT02004522) was 13.3 months compared with 9.9 months on ofatumumab (HR = 0.52; P < .0001).

Khan discusses this decisions impact and where he believes the future of PI3K inhibition is heading for treating patients with CLL or SLL.

Transcript:

0:08 | ODAC sort of went back and asked what we should do about this. So, the decision was that any new PI3K inhibitor that has to be approved, they have to really show phase 3 data comparatively rather than [an] accelerated approval. So that means we can no longer have accelerated approvals of PI3K inhibitors, and they have to do a longer study showing an OS benefit over the standard of care. And that will weed out any potential problems that come up with using PI3K inhibitors.

0:40 | So this decision really impacts in a way where, naturally, the drugs are available now, whether we can use it or not and future approvals might be slower as well. It doesn't really impact CLL much honestly, we never used to use a lot of PI3K inhibitors, because typically we use BTK inhibitors, or venetoclax based regimens, clinical trials, and only then do we look at these PI3K inhibitors. So, at the very least, now we have duvelisib available to us, but again, I don't think it's a big share of our treatment protocols in CLL. A good addition, but I do think this was a good decision so we can make it safer for PI3K inhibitors to be used.