FDA Approves Neoadjuvant and Adjuvant Durvalumab for Resectable Non-Small Cell Lung Cancer
On August 15, 2024, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer?utm_medium=email&utm_source=govdelivery) durvalumab (Imfinzi®) with platinum-containing chemotherapy as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after surgery, for adults with resectable (tumors that are 4 cm or larger or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) variants or anaplastic lymphoma kinase (ALK) rearrangements.
Efficacy was evaluated in AEGEAN (NCT03800134), a randomized, double-blind, placebo-controlled, multicenter trial involving 802 patients with previously untreated and resectable squamous or nonsquamous NSCLC (stage IIA–IIIB, per AJCC 8th edition). Patients were randomized 1:1 to receive either durvalumab or placebo with platinum-based chemotherapy every three weeks for up to four cycles (neoadjuvant treatment), followed by either continued single-agent durvalumab or placebo every four weeks for up to 12 cycles (adjuvant treatment).
The major efficacy outcome measures were event-free survival (EFS), as assessed by blinded independent central review, and pathologic complete response (pCR), as assessed by blinded central pathology review. Median EFS was not reached (95% CI = 31.9, not estimable [NE]) in the durvalumab arm and 25.9 months (95% CI = 18.9, NE) in the placebo arm (HR = 0.68; 95% CI = 0.53, 0.88; p = 0.0039). The pCR rate was 17% (95% CI = 13, 21) and 4.3% (95% CI = 2.5, 7) in the durvalumab and placebo arms, respectively. At the time of the prespecified interim analyses, overall survival (OS) was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment.
The most common adverse reactions reported in at least 20% of patients in the clinical trial were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of the patients who received neoadjuvant durvalumab, 1.7% were unable to receive surgery because of adverse reactions compared with 1% in the placebo arm.
For patients with a body weight of at least 30 kg, the recommended durvalumab dosage is 1,500 mg every three weeks (neoadjuvant treatment) or every four weeks (adjuvant treatment). For patients with a body weight less than 30 kg, the recommended durvalumab dosage is 20 mg/kg. Administer durvalumab prior to chemotherapy when both are given on the same day. View the full prescribing information for durvalumab at Drugs@FDA (mailto:https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm).
The applicant used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) to facilitate the FDA’s review.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program) or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:mailto:OncProjectFacilitate@fda.hhs.gov).