Outcomes with perioperative durvalumab (D) in pts with resectable NSCLC and baseline N2 lymph node involvement (N2 R-NSCLC): An exploratory subgroup analysis of AEGEAN.
Authors: Heymach John , Reck Martin , Mitsudomi Tetsuya , Taube Janis M. , Spira Alexander I. , Chaft Jamie E. , Doherty Gary J. , Mann Helen , Fouad Tamer M. , Harpole David H 
Published: June 2024

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Background: In the phase 3 AEGEAN study (NCT03800134), perioperative D + neoadj chemotherapy (CT) vs neoadj CT alone significantly improved the primary EPs of event-free survival (EFS) and pathological complete response (pCR; absence of residual viable tumor [RVT] in resection specimen, incl. primary tumor and sampled lymph nodes) with manageable safety in pts with R-NSCLC (modified ITT [mITT] population). Here, we report exploratory analyses of pts in AEGEAN with baseline N2 nodal status. Methods: Pts with Tx-naïve R-NSCLC (stage II–IIIB[N2]; AJCC 8th ed) were randomized (1:1) to 4 cycles of platinum-based CT plus D 1500 mg IV or placebo (PBO) Q3W before surgery (Sx), followed by D or PBO (Q4W, 12 cycles) after Sx. The mITT population excluded pts with known EGFR/ ALK alterations. Efficacy was assessed in an mITT subpopulation with baseline N2 nodal status (per investigator). Safety was assessed in all N2 R-NSCLC pts who had ≥1 Tx dose. Results: Of 740 pts in the mITT population, 366 (49.5%) had baseline N2 nodal status (D, n = 181; PBO, n = 185). In the N2 subgroup, 83.4% in the D arm and 84.9% in the PBO arm completed 4 cycles of platinum-doublet CT; 77.9% and 77.8%, respectively, had Sx; and 73.5% and 71.9% completed Sx. In the N2 subgroup, similar to the overall mITT population, EFS was prolonged in the D vs PBO arm (HR, 0.63 [95% CI: 0.43–0.90]); rates of pCR (16.6% vs 4.9%; difference, 11.7% [95% CI: 5.6–18.4]) and major pathological response (MPR, ≤10% RVT in primary tumor; 32.6% vs 15.1%; difference, 17.5% [95% CI: 8.8–26.0]) were higher in the D vs PBO arm. While EFS benefit in the D vs PBO arm was similar among pts with single- (HR, 0.61 [95% CI: 0.39–0.94]) or multi-station N2 (HR, 0.69 [95% CI: 0.33–1.38]), pCR benefit was less pronounced in multi-station pts (difference in pCR rate, 13.9% [95% CI: 6.6–21.7] for single-station N2 vs 3.8% [95% CI: –9.2–18.8] for multi-station N2). Among pts in the N2 subgroup who had Sx, similar proportions in the D and PBO arms had open (47.5% vs 50.0%) and minimally invasive procedures (50.4% vs 46.5%); 9.2% vs 11.1% had pneumonectomy (9.2% vs 9.6% in the overall mITT population). Of pts in the N2 subgroup who completed Sx, the proportion with R0 resection in the D vs PBO arm (94.7% vs 91.7%) was similar to that in the overall mITT population. Sx was delayed in a similar proportion who had Sx in the D vs PBO arm (19.9% vs 23.6%, respectively), most commonly for logistical reasons (e.g., scheduling issues). Among 394 pts who received Tx (N2 safety analysis subset; D, n = 200; PBO, n = 194), max grade 3/4 any-cause AEs occurred in 38.5% vs 41.8% in the D and PBO arm, respectively, similar to rates in the overall safety analysis set. Conclusions: With clinically meaningful improvement in efficacy, no adverse impact on Sx outcomes and a manageable safety profile, the addition of perioperative D to neoadj CT remains a potential new Tx option for pts with N2 R-NSCLC. Clinical trial information: NCT03800134 .