Using Solid Endpoint Strategies for Successful Cancer Trials

Moe Alsumidaie: What do the results from the AEGEAN study mean for healthcare professionals and patients?

Nabil Chehab: The long-term prognosis of patients with NSCLC, even among those with early-stage disease, is poor. With the Phase III AEGEAN trial, we are evaluating an immunotherapy—durvalumab—in combination with chemotherapy before surgery to prime the immune system, followed by adjuvant durvalumab to maintain immunosurveillance in patients with early NSCLC, to see if this approach induces a more robust immune response and improved outcomes.

Earlier this year, we shared an interim trial analysis that showed administering durvalumab in combination with chemotherapy before surgery demonstrated a statistically significant and meaningful improvement in pathologic complete response (pCR) compared to neoadjuvant (pre-surgical) chemotherapy alone. We also observed a statistically significant improvement in pathologic response (MPR). The safety and tolerability of adding durvalumab to neoadjuvant chemotherapy were consistent with the known profile for this combination. These high-level results from the ongoing trial are encouraging for patients and the multi-disciplinary teams who treat them because the surrogate endpoints of pCR and MPR have been associated with improved event-free survival in this setting.

MA: The results you reported relate to pathologic complete response. What is the significance of this endpoint for these patients and clinical trials?

NC: Surrogate endpoints such as pCR allow us to make an earlier assessment of efficacy after a patient completes neoadjuvant treatment and has shown promising potential as a surrogate endpoint for OS (overall survival). The increased rate of pCR seen in the AEGEAN trial suggests that adding durvalumab to neoadjuvant chemotherapy significantly increases the chance of eradicating lung cancer in Stage II/III patients with resectable NSCLC without decreasing the number of patients able to undergo successful surgery, compared to neoadjuvant chemotherapy alone.

As more data from AEGEAN and other randomized trials evaluating pCR as a surrogate endpoint are announced, it will inform a greater clinical understanding of the role of pCR and potentially lead to validation as a formal endpoint.

MA: Why is immunotherapy essential for this patient population?

NC: Treating resectable lung cancer early provides the best chance for a cure. Engaging the immune response with durvalumab before and after surgery in patients with early (Stage II/III) NSCLC is a new strategy. These early findings from AEGEAN could improve lung cancer patients’ survival in this potentially curative setting. This neoadjuvant and adjuvant strategy explored in AEGEAN builds on the expanded use of immunotherapy in earlier settings when lung cancer was more treatable. This is an exciting time to see if the benefits of immunotherapy can extend to the perioperative setting.

MA: How are you using the AEGEAN trial to show the value of precision medicine to cancer patients?

NC: The interim AEGEAN trial results demonstrate the potential of prioritizing precision medicine to deliver the treatment for the right patient at the right time. Biomarker testing is crucial in identifying those patients who might benefit the most. It also helps us ensure we’re not giving additional treatments to patients who will not benefit from them. Enrollment in the AEGEAN trial required that patients with Stage II/III NSCLC have confirmed PD-L1 status based on the Ventana PD-L1 immunochemistry assay before randomization and the absence of other known targetable biomarkers.

We have already seen the success of this approach in the ADAURA trial, which required confirmed positive epidermal growth factor receptor (EGFR) mutation for enrollment. We are committed to pushing the boundaries of science in immuno-oncology to change the practice of medicine.