Gabriel Garbaos

Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non–small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. Download a PDF of the Research Summary. We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P=0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.) QUICK TAKE VIDEO SUMMARYPerioperative Chemoimmunotherapy in Lung Cancer 02:08

Abstract Background: Recent trials have demonstrated the clinical benefit of immunotherapy in either the neoadjuvant or adjuvant resectable (R) NSCLC setting. AEGEAN (NCT03800134) is a randomized, double-blind, placebo (PBO)-controlled trial assessing neoadjuvant durvalumab (D) + chemotherapy (CT) followed by surgery (Sx) and adjuvant D in patients (pts) with R-NSCLC. Methods: Adults with treatment (Tx)-naïve R-NSCLC (stage II-IIIB[N2]; AJCC 8th ed) and ECOG PS 0/1 were randomized (1:1) to receive D 1500 mg or PBO IV + platinum-based CT (every 3 weeks [Q3W] for 4 cycles) before Sx, then further D 1500 mg or PBO IV (Q4W, up to 12 cycles). Pts were stratified by disease stage (II vs III) and PD-L1 tumor cell expression (&amp;lt;1% vs ≥1%, Ventana SP263). Pts with documented EGFR/ALK aberrations were excluded from the modified intent-to-treat (mITT) population for efficacy analyses. The primary endpoints were pathological complete response (pCR), evaluated centrally, and event-free survival (EFS; using RECIST v1.1), evaluated by BICR. Safety was assessed in all pts who received ≥1 study Tx dose. Results: Between Jan 2, 2019, and Apr 19, 2022, 802 pts were randomized to the ITT population (n=740 in the mITT population) of whom 799 received Tx (D arm, n=400; PBO arm, n=399). Baseline characteristics were largely balanced (mITT). Overall, 84.7% in the D arm and 87.2% in PBO arm completed 4 cycles of platinum-doublet CT and 77.6% and 76.7%, respectively, completed Sx (mITT). As of Nov 10, 2022 (data cutoff), median EFS follow-up in censored pts was 11.7 months (mITT). The pCR rate was significantly higher and EFS significantly prolonged in the D vs PBO arms (mITT) (Table). In the safety analysis set, maximum grade 3/4 any-cause AEs occurred in 42.3% vs 43.4% in the D and PBO arms, respectively, during the overall Tx period. Conclusions: The AEGEAN trial met both of its primary endpoints of improved pCR and EFS. Perioperative D plus neoadjuvant CT was associated with a manageable safety profile. Clinical trial identification: NCT03800134 (release date: January 11, 2019) Endpoint D arm PBO arm Tx effect P value pCR n/N: 63/366 (17.2%) n/N: 16/374 (4.3%) Difference in pCR (95% CI), %: 13.0 (8.7-17.6)a 0.000036 (assessed at IA)b EFS n events/N: 98/366 (26.8%) n events/N: 138/374 (36.9%) HR (95% CI): 0.68 (0.53-0.88)d 0.003902e Median (95% CI), months: NR (31.9-NR)c Median (95% CI), months: 25.9 (18.9-NR)c aCIs by stratified Miettinen and Nurminen’s method. bStatistical significance was achieved at the IA (402 pts; data cutoff, Jan 14, 2022); no testing was performed at FA. The statistically significant p-value of 0.000036 was based on a Cochran-Mantel-Haenszel test. cKaplan-Meier method. dStratified Cox proportional hazards model. eStratified log-rank test. CI, confidence interval; FA, final analysis; HR, hazard ratio; IA, interim analysis; NR, not reached. Citation Format: John V. Heymach, David Harpole, Tetsuya Mitsudomi, Janis M. Taube, Gabriella Galffy, Maximilian Hochmair, Thomas Winder, Ruslan Zukov, Gabriel Garbaos, Shugeng Gao, Hiroaki Kuroda, Jian You, Kang-Yun Lee, Lorenzo Antonuzzo, Mike Aperghis, Gary J. Doherty, Helen Mann, Tamer M. Fouad, Martin Reck. AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT005.