Adding Imfinzi (durvalumab) to the pre- and postoperative chemotherapy regimen improved outcomes — namely pathological complete response (pCR; the absence of detectable cancer cells) and event-free survival (EFS; absence of disease progression or signs of cancer) — in patients with non-small cell lung cancer, according to findings from the phase 3 AGEAN trial that were presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.
The addition of Imfinzi to chemotherapy led to improved pathologic complete response rates.
For patients who received the addition of Imfinzi (366 patients) the pCR rate was 17.2% compared with 4.3% in the placebo arm (374 patients), for an absolute difference of 13.0% at the final analysis.
Additionally, at a median follow-up of 11.7 months and an EFS maturity rate of 31.9%, the median EFS was not yet reached in the Imfinzi group, meaning that there had not been enough events to calculate an average, compared with 25.9 months in the placebo group. The 12- and 24-month EFS rates were both in favor of the Imfinzi arm over the placebo arm at 73.4% vs 64.5% and 63.3% vs 52.4%, respectively. These data were from the first planned interim analysis of the study.
“Regardless of disease stage, the addition of perioperative (Imfinzi) to neoadjuvant chemotherapy did not adversely affect the feasibility, type, approach or timing of surgery in patients with resectable NSCLC and resulted in numerically higher R0 resection (resection for complete cure or remission) rates,” Dr. Tetsuya Mitsudomi, a professor at the Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine in Osaka, Japan, added during the presentation.
AEGEAN enrolled patients with treatment-naïve stage 2A to 3B resectable NSCLC who were slated to receive a lobectomy, sleeve resection or bilobectomy as their planned surgery. Patients also needed to have an ECOG performance status of 0 or 1, indicating that they could perform all or most of their daily tasks independently, confirmed PD-L1 status, and no EGFR/ALK aberrations.
Eligible patients were randomly assigned to receive intravenous Imfinzi plus platinum-based chemotherapy every three weeks for four cycles or intravenous placebo plus platinum-based chemotherapy every three weeks for four cycles. After four treatment cycles, patients in both arms proceeded to surgery then received intravenous Imfinzi every four weeks for 12 cycles or intravenous placebo every four weeks for 12 cycles. Patients were stratified based on disease stage (2 vs 3) and PD-L1 expression (1% or greater vs less than 1%).
The main goals of the study were pCR and EFS. Key secondary end points were major pathologic response (MPR; meaning that there is 10% of the tumor remaining after post-surgery treatment), disease-free survival (DFS; time after treatment when no indications of cancer are present) and overall survival (OS; time from treatment until death from any cause). The efficacy analyses were of the Imfinzi-receiving group; this comprised all randomized patients without EGFR/ALK aberrations.
In the Imfinzi group, all patients received presurgical treatment and 84.7% completed four cycles of both chemotherapy agents. Most patients underwent surgery (80.6%), with 77.6% completing surgery.
Similarly in the placebo arm, nearly all patients received presurgical treatment (99.2%) and 87.2% completed four cycles of both chemotherapy agents. Most patients underwent surgery (80.7%), with 76.7% finishing surgery.
Patients in the Imfinzi arm with stage 2 (102 patients) and stage 3 (264 patients) disease had median durations of surgery of 3.5 hours (range, 1-24) and 3.5 hours (range, 1-10), respectively. In the placebo arm, patients with stage 2 (108 patients) and stage 3 (266 patients) disease had respective surgery durations of 3.4 hours (range, 1-24) and 3.3 hours (range, 1-24).
The median time from last presurgical treatment dose to surgery was 34 days (in both groups. The respective median times from surgery to first adjuvant treatment dose were 50 days (range, 22-136) compared with 52 days (range, 21-141).
Surgical delay was reported in patients in both the Imfinzi (17.3%) and placebo (22.2%) arms. Durations of delay lasted less than two weeks (9.5% vs 12.6%); two weeks to less than four weeks (4.1% vs 7.3%); four weeks to less than six weeks (2.4% vs 1.0%); and at least six weeks (1.4% vs 1.3%), respectively. Logistical reasons (9.5% vs 12.3%), adverse effects (AEs; 3.1% vs 4.3%), unresolved toxicity from previous study treatments (1.0% vs 1.3%) and other causes (4.4% vs 4.3%) were all listed as reasons for surgical delay.
Investigators used an open (49.2% vs 50.7%) or a minimally invasive (49.2% vs 47.0%) surgical approach in both the Imfinzi and placebo arms, respectively. Surgery types included lobectomy (88.1% vs 85.4%) and pneumonectomy (9.2% vs 9.6%).
Among patients who completed surgery, the rate of remission-gaining resection in the Imfinzi arm (284 patients) was higher than that of the placebo arm (287 patients), at 94.7% vs 91.3%, respectively. Patients in both arms also experienced macroscopic residual tumor after resection (R2 resection; 0.7% vs 0.7%) and microscopic residual tumor after resection (R1 resection; 4.2% vs 7.7%).
In the safety populations of Imfinzi (296 patients) and placebo (301 patients), any-grade side effects possibly related to surgery were reported in 40.2% vs 39.2% of patients, respectively. Moderate to severe (grade 3/4) events (8.4% vs 9.3%), serious side effects (11.1% vs 11.0%) and events resulting in death (2.0% vs 1.3%) occurred in both arms.
The most common any-grade side effects that are surgical related were procedural pain (10.8% vs 11.3%), wound complication (3.7% vs 4.9%), pneumonia (3.7% vs 3.1%), anemia (2.8% vs 3.4%), pneumothorax, which is a collection of air outside the lungs (3.1% vs 2.8%), cough (1.8% vs 3.7%) and difficulty or labored breathing (2.2% vs 3.1%).
Most patients in both the Imfinzi (59.1%) and the placebo arms (60.1%) experienced a surgical complication.
“With a clinically meaningful improvement in efficacy, no adverse impact on surgical outcomes and a manageable safety profile, the addition of perioperative (Imfinzi) to neoadjuvant chemotherapy is potential new treatment option for patients with resectable NSCLC,” Mitsudomi said in conclusion.
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