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The FDA expanded the on Thursday to include the perioperative treatment of resectable non-small cell lung cancer (NSCLC).

Approved in combination with platinum-based chemotherapy during the neoadjuvant phase and as monotherapy during the adjuvant phase, the PD-L1 inhibitor is specifically indicated for tumors that are node-positive or at least 4 cm, and that lack EGFR mutations or ALK rearrangements.

Support for the new indication came from AEGEAN, a placebo-controlled phase III trial that demonstrated improved event-free survival (EFS) and pathological complete response (pCR) rates with the addition of perioperative durvalumab to neoadjuvant chemotherapy.

"This approval brings an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer, who have historically faced high rates of recurrence even after chemotherapy and surgery," investigator John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said in a from drugmaker AstraZeneca. "When added both before and after surgery, durvalumab delivered a significant and meaningful improvement in outcomes in this curative-intent setting."

AEGEAN's efficacy analysis included 802 patients with squamous or non-squamous NSCLC that was previously untreated and considered resectable (stage IIA to select stage IIIB disease).

The risk for progression, recurrence, or death was reduced by 32% with the addition of durvalumab (HR 0.68, 95% CI 0.53-0.88, P=0.0039), with a median EFS not reached versus 25.9 months with placebo. Furthermore, pCR rates improved from 4.3% with placebo atop neoadjuvant chemotherapy to 17% with the addition of durvalumab. A descriptive analysis of overall survival showed no clear detriment with the addition of the checkpoint inhibitor, the FDA said.

Durvalumab now joins pembrolizumab (Keytruda) as the only FDA-approved perioperative immunotherapies for resectable NSCLC. The agency had previously approved neoadjuvant nivolumab (Opdivo) and both adjuvant pembrolizumab and atezolizumab (Tecentriq) in this setting as well.

Despite the approvals, FDA recently expressed concern over the combined neoadjuvant/adjuvant immunotherapy strategy, as recent studies have called into question the benefits of the adjuvant component of perioperative treatment.

At a meeting of the Oncologic Drugs Advisory Committee last month, all 11 panelists voted in agreement with FDA staff that the agency should mandate trials in the perioperative setting that can distinguish the effects of the different therapy phases.

According to , adverse events that occurred in 20% or more patients in AEGEAN included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of note, 4% of patients in each arm had delays to surgery due to adverse events following neoadjuvant treatment and some patients were unable to undergo surgery (1.7% in the durvalumab arm and 1% in the placebo arm).

Durvalumab also carries indications in stage III and metastatic NSCLC, small cell lung cancer, and other tumor types, including hepatocellular carcinoma and endometrial cancer.

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