Rethinking perioperative cancer trials
In a landmark decision, the FDA's Oncologic Drugs Advisory Committee (ODAC) unanimously voted to recommend new trial protocols for perioperative cancer studies.
The July 2024 ODAC meeting centered around AstraZeneca's Aegean trial, which evaluated the use of durvalumab plus chemotherapy before and after surgery in lung cancer patients. While the trial met its primary endpoint of event-free survival, the FDA raised concerns about the study design itself.
At the heart of the matter was a crucial question: Do patients truly need immunotherapy treatment both before and after surgery?
The FDA argued that AstraZeneca's trial design didn't adequately prove this necessity, potentially leading to patient over-treatment.
FDA calls for more rigorous trial designs
Dr. Erin Larkins, the acting division director, set the stage by emphasizing the need for future trials to include additional arms to justify the contribution of each treatment phase. This perspective reflects a growing concern about potential overtreatment in perioperative regimens, especially in resectable lung cancer cases where some patients might be cured by surgery alone.
Dr. Richard Pazdur, who leads the FDA's Oncology Center of Excellence, reminded the committee that we're dealing with resectable lung cancer. His intervention underscored the need for a higher standard of approval, particularly when considering long-term post-surgery immunotherapy treatment.
ODAC voted unanimously (11-0) in favor of requiring new trial design protocols for perioperative regimens in lung cancer
The ODAC voted unanimously (11-0) in favor of requiring new trial design protocols for perioperative regimens in lung cancer. These new designs should include adequate within-trial assessment of treatment phase contribution. In simpler terms, this means future trials may need to include a third arm (and possibly even a fourth) to compare treatment efficacy before and after surgery separately.
Implications for Drug Developers & Patients
This decision is marks a notable change for drug developers, not just in lung cancer but potentially across all solid tumor studies. While the vote specifically addressed lung cancer trials, it's likely that division directors in other oncology areas will extrapolate this decision when evaluating trial designs.
For patients, this could mean more targeted treatments and potentially less overtreatment. By requiring more comprehensive trial designs, we can better understand which patients truly benefit from immunotherapy before surgery, after surgery, or both.
Drug developers will need to adapt their trial designs to meet these new standards
This decision may require larger patient cohorts and longer study durations, but it will ultimately provide more robust and informative data. The FDA and AstraZeneca both presented strong cases at the ODAC meeting, demonstrating the complexity of this issue. While the Aegean trial showed a favorable risk-benefit profile with robust event-free survival data, the committee agreed with the FDA that future trials need to justify treatment on both sides of surgery more comprehensively.
This ODAC vote marks a significant shift in how we approach perioperative cancer trials. It's a testament to the FDA's commitment to ensuring that patients receive the most appropriate and effective treatments while minimizing unnecessary interventions.
Proceed with Precision
Precision's expert teams are led by industry veterans to ensure each study is meticulously designed to meet the highest standards of scientific rigor and patient safety. With our extensive experience in oncology and rare disease research, we guide you through complex regulatory landscapes, provide invaluable insights and support, and empower your program from first patient in to first patient impact.
