Real-world response assessment of immune checkpoint inhibition: comparing iRECIST and RECIST 1.1 in melanoma and non-small cell lung cancer patients

Objectives To compare immune response evaluation criteria in solid tumors (iRECIST) and response evaluation criteria in solid tumors (RECIST) 1.1 for response assessment of immune checkpoint inhibitor (ICI) therapy in a real-world setting in patients with melanoma and non-small cell lung cancer (NSCLC). Methods Two-hundred fifty-two patients with melanoma and NSCLC who received CTLA-4 inhibitor ipilimumab or PD-1 inhibitors nivolumab or pembrolizumab and who underwent staging CT of the chest and abdomen were retrospectively included. Treatment response evaluation according to the RECIST 1.1 and iRECIST guidelines was performed for all patients. Response patterns, as well as overall response rate (ORR), disease control rate (DCR), and time to progression (TTP), were compared between RECIST 1.1 and iRECIST. Results Out of 143 patients with progressive disease (PD) according to RECIST 1.1, 48 (33.6%) did not attain confirmation of progression (iCPD) as per iRECIST and six patients who were treated beyond RECIST 1.1 progression reached PD at a later point in time in iRECIST, resulting in a significant difference in TTP between iRECIST and RECIST 1.1 (618.3 +/- 626.9 days vs. 538.1 +/- 617.9 days, respectively (p < 0.05)). The number of non-responders as per RECIST 1.1 was 79, whereas it was 60 when using iRECIST. ORR was 28.5% for RECIST 1.1 and 34.1% for iRECIST, and corresponding DCR of 67.4% for RECIST 1.1 and 74.6% for iRECIST. Conclusion iRECIST was more suitable than RECIST 1.1 for capturing atypical response patterns to ICI therapy in patients with melanoma and NSCLC, resulting in differences in the assessment of treatment response. Clinical relevance statement Compared to RECIST 1.1, iRECIST may improve patient care and treatment decisions for patients with NSCLC or melanoma who are treated with immune checkpoint inhibitors in clinical routine.