FDA Panel Unanimously Recommends Randomized Data for PI3K Inhibitors in Hematologic Cancers

During an April meeting, the FDA’s Oncologic Drugs Advisory Committee voted 16-0 (with one abstention) in support of basing future approvals for phosphoinositide 3-kinase (PI3K) inhibitors on randomized data rather than single-arm clinical trials for hematologic cancers. Evidence presented at the meeting led members to vote in support of requiring randomized data for future drug approvals for this class in hematologic cancers.

The FDA noted at the meeting that single-arm trials have limitations that make them difficult to balance efficacy with toxicity, and randomized data presented at the hearing showed that PI3K inhibitors had higher fatal events and other serious adverse events than were shown in single-arm trials.

Four PI3K inhibitors are currently approved for hematologic malignancies and have received FDA approval based on single-arm data: idelalisib, copanlisib, duvelisib, and umbralisib. These agents have shown favorable efficacy outcomes, including durable overall response rates and improved progression-free survival in single-arm studies. However, post-marketing studies in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma (NHL) have indicated worse overall survival with PI3K inhibitors compared with patients in the control arm, as well as serious and fatal adverse events.

“While we definitely want to expedite drug development and make sure there are new therapies available to patients as soon as possible, it’s imperative, in our view, that we ensure those products are safe and effective,” Nicole Gormley, MD, acting division director of hematology products for the FDA, noted.

Source: FDA briefing document, April 2022