Response evaluation and survival prediction following PD-1 immunotherapy in patients with non-small-cell lung cancer: comparison of assessment methods.

Abstract

Immunotherapy using programmed cell death (PD)-1 blockers is a promising therapeutic modality for non-small-cell lung cancer (NSCLC). Therefore, defining the most accurate response criteria for immunotherapy monitoring is of great importance in patient management. This study aimed to compare the correlation between survival outcome and response assessment assessed by PET Response Criteria in Solid Tumors (PERCIST) 1.0, immunotherapy-modified PERCIST (imPERCIST), Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immunotherapy-modified RECIST (iRECIST) criteria in NSCLC patients. Methods: Seventy-two patients with NSCLC treated with nivolumab or pembrolizumab with baseline and follow-uP ¹⁸F-FDG PET/CT data were analyzed. The patients were categorized into responders (complete or partial response) and non-responders (stable or progressive disease) according to PERCIST1 and PERCIST5 (analyzing the SULpeak of one or up to five lesions), imPERCIST1, imPERCIST5, RECIST and iRECIST. The correlation between achieved response and overall survival (OS) was compared. Results: The overall response rate and the overall disease control rate of the study population were 29% and 74% respectively. The OS and progression free survival (PFS) of patients with complete and partial response were statistically comparable. The OS and PFS were significantly different between responders and non-responders (20.3 vs. 10.6 months, P = 0.001 for OS and 15.5 vs. 2.2 months p<0.001 for PFS respectively). Twenty-three (32%) patients with progressive disease according to PERCIST5 had controlled disease according to imPERCIST5; follow-up of patients showed that 22% of these patients had pseudoprogression. The overall incidence of pseudoprogression was 7%. The response rate was 25% and 24% according to PERCIST1 and PERCIST5 (P = 0.2), and 32% and 29% according to imPERCIST1 and imPERCIST5 (P = 0.5), respectively, indicating no significant difference between analyzing the SULpeak of only the most FDG-avid lesion and analyzing up to the 5 most FDG-avid lesions. Conclusion: The achieved response by all conventional and immunotherapy-modified methods was strongly correlated with patients’ survival outcome, with significantly longer OS and PFS in responders than in non-responders according to all assessed definitions. The most FDG-avid lesion according to the PERCIST and imPERCIST criteria accurately reflects the overall metabolic response.