FP02.04 NSCLC with TPS>90% could have Higher Possibility of Causing Severe irAE; Retrospective Investigation in one Institution

Abstract

Recently, immune checkpoint inhibitors (ICI) have been introduced into clinical treatment strategy for advanced or recurrent NSCLC. However, little is known about the relation between the risk of irAE and patients’ clinical backgrounds. In this research, we attempted to reveal which types of clinical backgrounds are likely associated with the development of severe irAE when they were treated with ICI. We have treated over 300 advanced or recurrent NSCLC with ICI in our institute since January 2016, and the results of TPS were obtained in 240 patients. We retrospectively analyzed the relationship between patients’ clinical backgrounds and severe irAE which caused discontinuation of treatment. We excluded patients who were treated with durvalmab because it has different treatment strategy from other ICIs. Patients' background is shown below. We defined TPS>90% as ultra-high TPS, because those patients are shown to have preferable response to ICI. All the patients with EGFR mutation received EGFR-TKI before ICI.Tabled 1first-line groupsecond or later-line groupcharasteristicAge, yearsmedian71.970.2range (95% C.I.)70.2-73.668.9-71.6Sexfemale18 ( 18.9%)56 ( 38.6%)Male77 ( 81.1%)89 ( 61.4%)Histologic diagnosisadenocarcinoma48 ( 50.5%)89 ( 61.4%)squamouscarcinoma38 ( 40.0%)37 ( 25.5%)others9 ( 9.5%)19 ( 13.1%)ECOG performance statusgood (0 or 1)80 ( 84.2%)96 ( 76.8%)poor (2 -4)15 ( 15.9%)29 ( 23.2%)TPShigh expression (>50%)67 (70.5%)40 (27.6%)low expression (1-49%)22 (23.2%)56 (38.6%)negative (<1%)6 ( 6.3%)49 (33.8%)ultra-high expression (>90%)32 ( 33.7%)19 ( 13.1%)Driver mutationno92 ( 96.8%)105 ( 72.4%)yes3 ( 3.2%)40 ( 27.6%)EGFR / KRAS / HER2 / others0 / 2 / 1 / 036 / 1 / 2 / 1ICIpembrolizumab84 ( 88.4%)57 ( 39.3%)nivolumab0 ( 0%)62 ( 42.8%)atezolizumab11 ( 11.6%)26 ( 17.9%) Open table in a new tab Forty-six had severe irAE of any grade of ILD or >Grade3 AE, and most of them were treated with steroids. Nineteen of them received ICI subsequently. Univariate analysis indicated that TPS>50%, first-line treatment and administration of pembrolizumab showed significantly higher possibility of severe irAE (p<0.05, p<0.001, p<0.05, respectively). Furthermore, patients with ultra-high TPS was likely to experience severe irAE compared to other groups (p<0.01). When we examine the patients in first-line treatment, only ultra-high TPS showed statistically higher tendency of irAE (p<0.05). However, in second or later-line patients, no clinical backgrounds indicated the higher risk of irAE. No difference was observed in response rate between ultra-high and other group in first-line treatment (71.9%, 61.9% respectively, p=1.0). In later-line, ultra-high group showed better response rate than others (52.6%, 19.8% respectively, p=0.032). However, no differences were observed in time to treatment failure and OS between ultra-high and others. In 1st-line patients, TTF of ultra-high and others was 207days and 175days (p=0.306), OS was 727days and 742days, respectively (p=0.74). In later-line, TTF was 107days and 70days(p=0.109),and OS was 511days and 308days (p=0.448). Patients with ultra-high TPS had higher possibility of irAE especially when they received ICI for first-line. However, no difference was observed in OS between two groups. In our investigation, survival was not translated from better response in ultra-high group.