FDA Approves Neoadjuvant, Adjuvant Durvalumab for Resectable NSCLC

The US Food and Drug Administration 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 tumors ≥4 cm and/or node-positive non-small cell lung cancer (NSCLC) and no known EGFR mutations or ALK rearrangements.

The efficacy and safety of the treatment was evaluated in the AEGEAN trial, which was a randomized, double-blind, placebo-controlled multicenter trial. The trial evaluated the treatment in 802 patients with previously untreated and resectable squamous or nonsquamous NSCLC in stage IIA to select stage IIIB. The AEGEAN trial investigators randomized patients 1:1 to receive neoadjuvant treatment with durvalumab or placebo with platinum-based chemotherapy every 3 weeks for up to 4 cycles. This was followed by adjuvant treatment with continued single-agent durvalumab or placebo every 4 weeks for up to 12 cycles.

The major efficacy outcome measures were event-free survival (EFS) by blinded independent central review assessment and pathological complete response (pCR) by blinded central pathology review.

The study showed that the median EFS was not reached (95% CI, 31.9 months to not estimable) in the durvalumab arm and 25.9 months (95% CI, 18.9 months to not estimable) in the placebo arm (hazard ratio, 0.68; 95% CI, 0.53-0.88; P=.0039).

The pCR rate was 17.0% in patients receiving durvalumab, compared with 4.3% in the patients receiving placebo.

“At the time of the prespecified interim analyses, overall survival was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment,” FDA officials said in a news release announcing the approval.

Anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash were the most common adverse events reported. Among the patients receiving neoadjuvant durvalumab, 1.7% were unable to receive surgery due to adverse reactions. The rate was 1% in the patients who were receiving placebo.

For patients with a body weight of ≥30 kg, the recommended neoadjuvant dose of durvalumab is 1500 mg every 3 weeks and every 4 weeks for adjuvant treatment, according to the FDA. For patients with a body weight of <30 kg, the recommended durvalumab dosage is 20 mg/kg. Durvalumab should be administered prior to chemotherapy when administered on the same day.

Source: FDA