Durvalumab (D) Compared To Maintenance Chemotherapy (Soc) In Patients (Pts) With Metastatic Non-Small Cell Lung Cancer (Nsclc): Results From The Randomized Safir02 Lung-Immuno Trial

PDL-1 inhibitors such as D have shown efficacy in the management of advanced NSCLC. We investigated the effect of D as a maintenance strategy after chemotherapy in the SAFIR02-LUNG Immuno substudy. ALK-/EGFRwt NSCLC pts after a CR/PR/SD to 4 cycles of platinum-based chemotherapy were eligible. Pts were enrolled in 2 substudies, based on NGS + CGH performed centrally on a mandatory tissue or liquid biopsy. The bio-guided substudy, for NSCLC with somatic alterations (including KRAS, STK11, BRAF mutations), will be reported separately. In the immuno substudy, pan-negative NSCLC pts were randomized 2:1 either on D or SoC. The primary endpoint was Progression-Free Survival (PFS). A prespecified subgroup analysis was performed according to positive (>=1%) or negative (<1%) PDL-1 immunohistochemistry (IHC) expression. Among the 183 randomized pts (121 were on D), median age was 62, 37.7% were female, 12.6% never-smoker, 92.9% had a non-squamous. 162 pts had progressed or died. With a median follow-up of 23.8 months (mo), median PFS was 3.0 mo (95% confidence interval [CI], 2.3 to 4.4) with D versus 3.0 mo (95%CI=2.0-5.1) with SoC (HR for disease progression or death 0.87; 95%CI=0.63 to 1.22; p=0.426). Median OS was 17.0 mo (95%CI=12.1-19.5) with D versus 14.9 mo (95% CI=10.5-22.0) with SoC (HR for death 0.91; 95%CI=0.61-1.37; p=0.661). PDL-1 IHC was performed on 60 samples (42 on D and 18 on SoC). The HR for PFS was 0.29 (95%CI=0.11-0.75; p=0.011) in PDL-1+ pts treated by D compared to SoC vs 0.71 (95%CI=0.31-1.60; p=0.408) in PLD-1- pts (interaction p=0.036). The HR for OS was 0.32 (95%CI=0.12-0.83; p=0.020), vs 1.20 (95%CI=0.48-2.99; p=0.701) in PDL-1+ and PDL-1 pts respectively (interaction p=0.039). Grade 3 or 4 treatment-related adverse events occurred in 15 pts out of 121 pts on D (17.1%). In this substudy, pts were negatively selected based on a central molecular analysis. In this population, maintenance D, vs SoC, did suggest a positive effect on PFS and OS in the PDL-1 positive subgroup but not in the overall population. This finding requires validation in larger studies. There was no new finding in D toxicity profile.