Preoperative immune checkpoint inhibitor therapy may be of benefit in early-stage NSCLC. This multicenter trial assesses the feasibility of neoadjuvant durvalumab.
Pts IB>4cm–IIIA, non N2 resectable NSCLC (TNM 8th edition) receive 3 courses of durvalumab 750 mg (days 1, 15, 29) then underwent resection, between day 2 and 14 after last infusion. Primary endpoint was % of complete surgical resection (R0); secondary endpoints safety, overall survival (OS), disease-free survival (DFS), time between first infusion and surgery, response rate (RECIST 1.1), major pathological response (MPR).
50 pts included between April 2017 and August 2019. 46 eligible. 67.4% males, median age, 61 y; all ECOG PS 0-1; 98% smokers; 23 adenocarcinoma, 19 squamous; clinical stages IB/IIA/IIB/IIIA n = 5/13/27/1. Among the 46 operated pts, 9 had pneumonectomy, 31 lobectomy, 3 bilobectomy, and 3 an exploratory thoracotomy (2 pleural carcinosis; 1 esophageal invasion). Study was stopped because of an excess in 90-day postoperative mortality (4 deaths, 9%, 1 unknown (died at home); 2 acute respiratory failures; 1 tracheal fistula). 3 out of 4 deceased pts had cardiovascular comorbidities (3 arterial hypertensions; 1 peripheral arterial disease; 1 ischemic heart disease), or other (1 severe COPD; 1 diabetes). 41 pts were R0 (90%). There was no Grade 3-5 durvalumab related AEs. 4/46 pts had PR, 36 SD and 6 PD. Median time between first infusion and surgery was 37 (range: 29-46). Median OS and DFS was not reached; 18-m OS: 88.7% [95% CI: 74.9-95.1] 18-m RFS: 69.7% [95% CI: 53.2-81.3].
Enrollment was stopped because of excessive 90-day postoperative mortality. Deaths were due to postoperative complications possibly related to comorbidities and not to direct durvalumab toxicity. MPR rates and ongoing correlative analyses will be presented.
NCT03030131.
French Cooperative Thoracic Intergroup (IFCT).
AstraZeneca.
M. Wislez: Advisory/Consultancy: Boeringher Ingelheim; Speaker Bureau/Expert testimony: Boeringher Ingelheim; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: Roche; Advisory/Consultancy: MSD; Speaker Bureau/Expert testimony: MSD; Travel/Accommodation/Expenses: MSD; Non-remunerated activity/ies: MSD; Advisory/Consultancy: BMS; Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony: Amgen; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (self): BMS. J. Mazieres: Advisory/Consultancy: Roche; Research grant/Funding (institution): Roche; Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengruii; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda. A. Lavole: Travel/Accommodation/Expenses: BMS. G. Zalcman: Honoraria (self): Pfizer; Research grant/Funding (institution): Roche; Advisory/Consultancy: BMS; Honoraria (self): BMS; Travel/Accommodation/Expenses: BMS; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD. O. Molinier: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses: Boehringer Ingelheim. M.A. Massiani: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Elivie; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: MSD. D. Damotte: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (self): MedImmune; Honoraria (self): AbbVie; Travel/Accommodation/Expenses: AbbVie. M. Antoine: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca. V. Westeel: Honoraria (self): Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: BMS; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): BMS; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Fresenius; Research grant/Funding (institution): Merck-Serono. All other authors have declared no conflicts of interest.