Baseline characteristics of NSCLC first-line immunotherapy super-responders in three European lung cancer centers: An ENDEAVOUR-IMIGO project.

Abstract

8578 Background: Immune-checkpoint inhibitors (ICI) are part of first-line treatment concepts for most patients with metastatic non-small cell lung cancer (NSCLC) without targetable driver mutations. Still, long-term response is rare and data on predictive biomarkers limited. Methods: As part of the Daiichi Sankyo ENDEAVOUR programme supporting young LC researchers, the ENDEAVOUR-IMIGO working group aims to explore novel predictive biomarkers for ICI response with a focus on imaging data. We present the baseline characteristics of first-line ICI “super-responders” with PFS ≥24 months, derived from three independent cohorts from Austria, Italy and the Netherlands. Also, an exploratory single-center analysis compared ICI super- to non-responders (PFS<6M) matched for age, sex, histology, PD-L1 positivity, stage and ECOG performance status. Results: The Linz (Austria) cohort reported 50 (12.4%) super-responders out of a total of 402 patients, the Milan cohort (Italy) 45 out of 283 (15.9%), and the Groningen cohort (Netherlands) 46 (10.7%) out of 428. As shown in table 1, all cohorts had a high prevalence of adenocarcinomas, with KRAS mutations present in nearly half of patients and a mean PD-L1 expression of approximately 50%. In the Austrian cohort, matched baseline data showed a higher frequency of systemic steroids among non-responders, and lower absolute neutrophil count as well as neutrophil-to -lymphocyte ratio in super-responders. Conclusions: Baseline characteristics of ICI super-responders were similar in three European cohorts, with a majority of high-PD-L1 expressing adenocarcinomas. Exploratory matched analyses from one cohort showed implications of baseline systemic steroid treatment as well as of differential blood cell count. Linz Milan Groningen PFS < 6M n = 50(matched) PFS ≥ 2Y n = 50 p value < 6M vs. ≥ 2Y PFS ≥ 2Y n = 45 PFS ≥ 2Y n = 46 Male sex, n (%) 24 (48) 25 (50) 0.841 34 (75.5) 22 (48) Age <70, n (%) 14 (28) 15 (30) 0.826 15 (33.3) 34 (74) ECOG, n (%) 0 25 (50) 24 (48) 0.768 21 (47) 18 (39) 1 16 (32) 19 (38) 23 (51) 23 (50) 2+ 9 (18) 7 (14) 1 (2) 5 (11) Histological subtype, n (%) Adenocarcinoma 36 (72) 36 (72) 0.341 30 (67) 33 (72) Squamous cell carcinoma 12 (24) 14 (28) 6 (13) 7 (15) Other 2 (4) 0 (0) 9 (20) 6 (13) PD-L1 expression %, mean (SD) 41.9 (36.8) 48.9 (38.8) 0.403 52.3 (35.4) 54.0 (39.0) Brain metastases, n(%) 16 (32) 13 (26) 0.509 14 (31) 7 (15) KRAS mutation, n (%) 12 (35) 18 (50) 0.214 19 (42) 23 (50) Treatment, n (%) Chemo-ICI combination 29 (58) 38 (76) 0.056 18 (40) 19 (41) ICI-monotherapy 21 (42) 12 (24) 27 (60) 27 (59) Systemic steroid treatment, n(%) 17 (34) 6 (12) 0.009 12 (27) 8 (17) Absolute neutrophil count (G/L), mean (SD) 11.5 (8.7) 7.7 (2.9) 0.015 6.8 (3.2) 7.3 (2.6) Absolute lymphocyte count (G/L), mean (SD) 1.7 (3.7) 1.4 (0.7) 0.071 1.9 (0.7) 1.6 (0.7) Neutrophil-to-lymphocyte ratio, mean (SD) 13.4 (11.0) 7.2 (5.2) 0.006 4.4 (3.6) 5.9 (4.0)