The FDA’s Oncologic Drugs Advisory Committee on Thursday strongly supported changing clinical trials for non-small cell lung cancer drugs given in the perioperative setting, pointing out the need for a more nuanced approached to treatments before and after surgery.
The FDA’s Oncologic Drugs Advisory Committee on Thursday unanimously backed the need to change trial designs in perioperative non-small cell lung cancer, highlighting the need to clearly elucidate the contributions of investigational treatments when given either before or after therapy.
Doctors and patients need to know “which phase of treatment is contributing what,” David Mitchell, president of the nonprofit Patients for Affordable Drugs and acting consumer representative, said during the adcomm meeting. “The thought of giving patients a year of adjuvant therapy with the risks involved, the toxicities involved … not knowing if it’s doing any good whatsoever, is not acceptable.”
The panel of outside experts voted 11-0 with no abstentions.
Thursday’s meeting was brought about by AstraZeneca’s bid to expand the label of Imfinzi (durvalumab), proposing a perioperative regimen of the PD-L1 blocker in patients with non-resectable non-small cell lung cancer (NSCLC). The pharma’s supplemental application rests on the Phase III AEGEAN study, which administered Imfinzi with chemotherapy before surgery, and as a monotherapy after the operation.
The trial hit its primary efficacy endpoint, inducing a 17.2% pathological complete response rate, versus 4.28% in the placebo arm. The Imfinzi-based regimen also led to significantly better event-free survival.
However, in a joint briefing document issued prior to Thursday’s adcomm meeting, internal FDA staffers pointed to the “potential overtreatment” with AstraZeneca’s proposed regimen as giving Imfinzi before and after surgery could expose patients to excessive levels of the chemoimmunotherapy, leading to a heightened burden of adverse events.
AEGEAN, the FDA’s staffers noted, was not adequately designed to “determine if the benefit observed in the post-surgery period requires the addition of the adjuvant durvalumab phase.”
Ravi Madan, medical oncologist at the National Cancer Institute, suggested potential changes to study design during the adcomm meeting. “The only path isn’t a Phase III with an extra two arms, an extra 1,500 patients,” he said. “The other path is a more deliberate pre-registration approach, whether it’s preclinical or Phase II trials … that can better inform a Phase III.”
On the question of AstraZeneca’s application, the panelists did not recommend asking the pharma to run another, better-designed trial—despite the notable uncertainties regarding the necessity for both the adjuvant and neoadjuvant phases of Imfinzi.
“From an idealist’s perspective, it would be great to do this [additional] trial,” which could take five or six more years, Madan said. “But … there’s a pragmatic component here.”
“I think to delay this at this point is very complicated for patients and their providers,” he commented.
