123P Updated safety of perioperative durvalumab for resectable NSCLC in AEGEAN

In the phase III AEGEAN trial, perioperative durvalumab (D) + neoadjuvant (neoadj) chemotherapy (CT) significantly improved event-free survival and pathological complete response versus neoadj CT alone with a manageable safety profile in patients (pts) with resectable (R) NSCLC. We report updated safety from AEGEAN with ∼9 months additional study follow-up. Adults with treatment (Tx)-naïve R-NSCLC (stage II–IIIBN2; AJCC 8th ed.) were randomised 1:1 to receive platinum-based CT + D or placebo (PBO) IV (Q3W, 4 cycles) before surgery (Sx), followed by adjuvant (adj) D or PBO (Q4W, 12 cycles) post-Sx. This ad hoc safety analysis was required by US health authorities to support regulatory filing. Adverse events (AEs; graded per NCI CTCAE v5.0) were assessed for each protocol-specified Tx period in all randomised pts who received ≥1 Tx dose. Overlapping with the adj period, the post-Sx period was defined as the date of Sx (inclusive) to the earliest of 90 days post-Sx or the first dose of subsequent anticancer Tx. 799/802 randomised pts received study Tx. As of 14 Aug 2023 (data cutoff), median overall Tx duration was 44.9 and 36.6 weeks in the D and PBO arms, respectively. 704/799 (88.1%) had completed 4 cycles of neoadj D/PBO, 651/802 (81.2%) had undergone Sx, and 337/799 (42.2%) had completed adj D/PBO; only 7/799 pts (0.9%) remained on adj Tx. The rate of max. grade 3/4 any-cause AEs was similar between Tx arms during the neoadj and overall Tx periods (Table); max. grade 3/4 any-cause AEs occurred less frequently during the post-Sx and adj periods. Most pts with AEs leading to discontinuation of D/PBO or CT had such events in the neoadj period, and of those pts with AEs leading to death, most had such events during the post-Sx period (Table). Table: 123PAE, n (%)NeoadjuvantPost-SxAdjuvantOverallD n=401PBO n=398D n=325PBO n=326D n=266PBO n=254D n=401PBO n=398Any365 (91.0)357 (89.7)235 (72.3)219 (67.2)223 (83.8)190 (74.8)387 (96.5)379 (95.2)Possibly related to Txa,b330 (82.3)313 (78.6)83 (25.5)36 (11.0)128 (48.1)74 (29.1)350 (87.3)325 (81.7)Max. grade 3/4130 (32.4)145 (36.4)55 (16.9)41 (12.6)41 (15.4)27 (10.6)174 (43.4)172 (43.2)Leading to death8 (2.0)4 (1.0)13 (4.0)9 (2.8)4 (1.5)2 (0.8)23 (5.7)15 (3.8)Leading to Tx discontinuationa54 (13.5)31 (7.8)––26 (9.8)10 (3.9)78 (19.5)40 (10.1)Serious83 (20.7)66 (16.6)61 (18.8)51 (15.6)40 (15.0)26 (10.2)156 (38.9)126 (31.7)aD/pbo or CT. bInvestigator-assessed causality. Open table in a new tab aD/pbo or CT. bInvestigator-assessed causality. There were no new safety signals observed for perioperative D + neoadj CT at this update, and the adj D portion of the AEGEAN regimen was well tolerated in pts with R-NSCLC.