Neoadjuvant/Adjuvant Durvalumab Approved for Resectable Non–Small Cell Lung Cancer
Expert Perspectives · Lyn Brook · 2024-08-20
The FDA has approved durvalumab (Imfinzi®, AstraZeneca) with platinum-containing chemotherapy as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after surgery, for adults with resectable—defined as tumors ≥4 cm and/or node-positive—non–small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
Why it matters: “Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable NSCLC,” wrote John Heymach, MD, PhD, Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center, and colleagues, in their published results of the AEGEAN trial (NCT03800134), on which approval was based. “Perioperative regimens may combine benefits of both to improve long-term outcomes.”
What they studied: Efficacy was measured in the phase 3, double-blind, placebo-controlled trial which enrolled 802 patients with previous untreated ad resectable squamous or non-squamous NSCLC. Patients were randomized 1:1 to receive either durvalumab or placebo plus platinum-based chemotherapy every three weeks for up to four cycles as neoadjuvant treatment, followed by continued single-agent adjuvant treatment every four weeks for up to 12 cycles.
The primary efficacy outcomes measured were event-free survival as assessed by Blinded Independent Central Review and pathological complete response as assessed by Blinded Central Pathology Review.
What they found: At the time of assessment, median event-free survival was not reached in the durvalumab arm and was 25.9 months in the placebo arm. The rate of pathological complete response was 17% in the durvalumab arm and 4.3% in the placebo arm. Despite overall survival not being formally tested for statistical significance, a descriptive analysis revealed no clear detriment.
Adverse events: The most common adverse events experienced in ≥20% of patients receiving durvalumab were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of the patients who received neoadjuvant durvalumab, 1.7% were unable to receive surgery due to adverse reactions compared with 1% in the placebo arm.
Conclusion: “In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents,” concluded Dr. Heymach and colleagues.
Instructions: The recommended dosage of durvalumab is based on body weight. For patients with a body weight of ≥30 kg, it is recommended they receive 1,500 mg of durvalumab every three weeks as neoadjuvant treatment and every four weeks as adjuvant treatment. For patients with a body weight of <30 kg, it is recommended they receive 20 mg/kg of durvalumab. When administered on the same day as chemotherapy, durvalumab should be administered first.