Abstract 123P
Background
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.
Methods
Adults with treatment (Tx)-naïve R-NSCLC (stage II–IIIB[N2]; 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.
Results
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: 123P
| AE, n (%) | Neoadjuvant | Post-Sx | Adjuvant | Overall | ||||
| D n=401 | PBO n=398 | D n=325 | PBO n=326 | D n=266 | PBO n=254 | D n=401 | PBO n=398 | |
| Any | 365 (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,b | 330 (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 3/4 | 130 (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 death | 8 (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 discontinuationa | 54 (13.5) | 31 (7.8) | – | – | 26 (9.8) | 10 (3.9) | 78 (19.5) | 40 (10.1) |
| Serious | 83 (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.
Conclusions
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.
Clinical trial identification
NCT03800134.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Emily Smyth, MSc (Manchester, UK), and Andrew Gannon, MS, MA (New York, NY, USA) of Ashfield MedComms, an Inizio Company.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Reck: Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, Daiichi Sankyo, Janssen; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, Daiichi Sankyo, Janssen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, Daiichi Sankyo, Janssen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Sanofi. R. Zukov: Other, Personal and Institutional, Principal Investigator: A.I.Kryzhanovsky Krasnoyarsk Regional Clinical oncology center. G.E. Garbaos: Non-Financial Interests, Institutional, Principal Investigator: Fundacion Estudios Clínicos. G. Pasello: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Amgen, Roche, Janssen, Novartis; Non-Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Non-Financial Interests, Institutional, Funding: MSD; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, Lilly, Amgen, Roche, Janssen. T. Fouad: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Morgan, R. Doake: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Invited Speaker: Spectrum; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Invited Speaker: Takeda. All other authors have declared no conflicts of interest.