Intro: The FDA’s Oncologic Drugs Advisory Committee (ODAC) has challenged AstraZeneca’s perioperative clinical trial for resectable non-small cell lung cancer (NSCLC) highlighting the need for a more precise evaluation of each treatment phase's contribution. 

Why it’s notable:

• The FDA’s Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended overhauling perioperative clinical trial designs for resectable non-small cell lung cancer (NSCLC) to assess the contribution of each treatment phase separately. The recommendation comes in response to AstraZeneca’s application to approve Imfinzi as a treatment both before and after tumor-removal surgery in early-stage NSCLC. The proposed regimen involves the pre-operative use of Imfinzi combined with chemotherapy, followed by the post-operative use of Imfinzi as a monotherapy.

• In AstraZeneca’s phase 3 AEGEAN study, which met its primary endpoint, the use of Imfinzi before and after tumor-removal surgery reduced the risk of recurrence, progression, or death by 32% in patients with resectable stage 2 to stage 3b NSCLC compared to chemotherapy alone. However, due to the trial design, it was not possible to individually assess the contributions of the pre-operative and post-operative stages of the therapy.

POV: FDA scrutiny of perioperative trials may lead to a delay in timelines for drug makers, but ultimately improve patient treatment

• The scrutiny on perioperative regimen designs may delay the approval and market access of new treatments. In its ODAC briefing document, the FDA has urged companies, including AstraZeneca, to design trials that evaluate both phases of perioperative treatment. As the FDA considers whether AstraZeneca will need a new trial to clarify the contributions of each phase of the regimen, existing treatments like BMS's Opdivo and Merck’s Keytruda might also face scrutiny for similar flaws in their trial design. 

• The FDA has previously expressed concerns about overtreatment stemming from continuous neoadjuvant-adjuvant trial designs that do not isolate the benefits of each treatment phase. Meanwhile, some doctors on the panel expressed frustration over their inability to clearly inform patients about the benefits and risks. The call for trials that evaluate the efficacy of each phase separately could lead to more complex, expensive, and time-consuming studies. However, it aims to ensure that treatments are both effective and safe, potentially reducing the risk of overtreatment and unnecessary toxicity. 

Read the news story here.