Imfinzi’s perioperative approval comes after both the FDA’s staffers and a panel of external experts expressed concerns about overtreatment when using the PD-L1 blocker both before and after surgery.
AstraZeneca touted two lung cancer victories on Thursday with its blockbuster PD-1 inhibitor Imfinzi (durvalumab) securing the FDA’s nod for a perioperative label expansion in non-small cell lung cancer, as well as the regulator’s Priority Review and Breakthrough Therapy designations for small cell lung cancer.
The perioperative approval came as a bit of a surprise. Last month, the FDA’s Oncologic Drugs Advisory Committee expressed strong skepticism about using Imfinzi both before and after surgery and flagged the risk of overtreatment. Due to these concerns, the advisory committee unanimously supported the need to change trial designs for drugs being proposed as perioperative treatments.
David Mitchell, president of the Patients for Affordable Drugs and who acted as consumer representative in the adcomm meeting, insisted that doctors need to know “which phase of treatment is contributing what,” adding that it is “not acceptable” to expose patients to a year of adjuvant treatment and its toxicities “not knowing if it’s doing any good whatsoever.”
The FDA’s internal reviewers expressed similar concerns. In a joint briefing document released prior to the adcomm meeting, the regulator’s staffers maintained that if Imfinzi’s therapeutic benefit mostly came from the neoadjuvant phase, then using it as an adjuvant treatment “would expose patients to overtreatment and its attendant safety risks and additional treatment burden without added clinical benefit.”
Despite these uncertainties and safety risks, the FDA’s external advisors could not recommend asking AstraZeneca to run another trial.
“From an idealist’s perspective, it would be great to do this [additional] trial,” Ravi Madan, medical oncologist at the National Cancer Institute, said during the adcomm meeting. That study could take five to six more years, however, which in turn could keep an effective treatment out of patients’ reach, according to Madan.
“I think to delay this at this point is very complicated for patients and their providers,” Madan said.
The FDA did not specifically address these concerns in its approval notice on Thursday. Under the expanded label, Imfinzi can be given with platinum-based chemotherapy in patients with resectable non-small cell lung cancer who have no known EGFR or ALK mutations. After surgery, Imfinzi can be given as a single-agent regimen.
Earlier on Thursday, the FDA also granted Imfinzi its Priority Review and Breakthrough Therapy designations for the treatment of limited-stage small cell lung cancer. A decision for Imfinzi in this indication is expected in the fourth quarter of 2024.
AstraZeneca is backing Imfinzi’s small cell lung cancer FDA bid with data from the Phase III ADRIATIC study, which showed that Imfinzi could lower the risk of death by 27% in these patients as compared with placebo. The PD-L1 blocker also reduced the risk of disease progression or death by 24%.
