Inter-reader reliability of immune-specific response criteria (irRECIST & iRECIST).

e21108 Background: RECIST 1.1 can underestimate treatment benefits of immunotherapy, with irRECIST and iRECIST accounting for atypical responses. Inter-reader discordances are known to occur in a dual reader paradigm. Our objective is to compare inter-reader reliability between RECIST 1.1, irRECIST, and iRECIST. Methods: This is a retrospective analysis of advanced NSCLC patients treated with pembrolizumab at our institution as part of the KEYNOTE-001 study. All trial imaging was interpreted by two radiologists. RECIST 1.1, irRECIST, and iRECIST categorical responses and agreement for progressive disease (PD) was compared by kappa statistic. Time to progression (TTP) or time to censor was compared between readers by paired t test. Relationship to disease progression and overall survival (OS) was assessed by log rank. Results: Of 98 patients, 77 had baseline and subsequent imaging available for 5.8 mean timepoints with 42.9 weeks of follow up. From this group, 45 patients had imaging beyond iUPD for confirmation and were analyzed. PD occurred by reader 1, reader 2 in 34, 33 patients by RECIST 1.1 (k = 0.591, CI = 0.320-0.863), 31, 29 patients by irRECIST (k = 0.501, CI = 0.234-0.768), and 27, 22 patients by iRECIST iCPD (confirmed-PD) (k = 0.690, CI = 0.485-0.896). There was no significant difference in reader agreement by RECIST 1.1, irRECIST, iRECIST (p = 0.38, 0.60, 0.26). There was a significant difference in time to progression between RECIST 1.1, irRECIST and iRECIST, with median PFS 3.4 months (2.6-4.6), 4.7 (3.5-6.8) and 8.7 (6.9-14.5) (p < 0.0001). PD by any criteria was not significantly correlated with OS. Conclusions: PD confirmation by iRECIST resulted in substantial reader agreement compared to moderate reader agreement by RECIST 1.1 and irRECIST. There were significant differences in TTP between the criteria, with iRECIST having the longest TTP. PD by each criteria did not correlate with a significant difference in OS.[Table: see text]