P1.04-70 Application of Tumor Kinetics for Evaluation of Hyperprogression in Immune Checkpoint Inhibitor Treatment for Non-Small Cell Lung Cancer

Abstract

Immune checkpoint inhibitors (ICIs) have suggested substantial options for treatment in advanced non-small cell lung cancer (NSCLC) without driver oncogenes. However, existing criteria for response assessment have limitations in differentiating categories of disease progression upon ICI treatment: primary resistance, pseudoprogression or hyperprogression (HPD). This study was aimed to investigate a real-world feasibility of pre- and on-treatment tumor kinetics for ICIs-specific response assessment in NSCLC. We retrospectively recruited stage III/IV NSCLC patients treated with anti-PD-1/PD-L1 monotherapy after failure of first-line platinum-doublet chemotherapy (n=91) between June 2016 and October 2018. Based on medical records from response-evaluable patients, we analyzed tumor kinetics prior and upon ICI treatment using ratio of tumor growth rate (TGR ratio, TGRR), tumor growth kinetics (TGK ratio, TGKR) and difference in TGR (delta TGR, ΔTGR), respectively. HPD was defined as TGRR≥2, TGKR≥2 and ΔTGR >50%. After excluding 18 patients without CT scan after start of ICIs, 73 patients were enrolled. Of response-evaluable patients, 47 patients (64%) stopped ICI treatment due to disease progression or death. Overall response rate by RECIST v1.1 was 16.4% (12/73) and disease control rate was 62% (45/73). HPD patients was 12% (9/73) and 15% (11/73) when defined by TGRR and TGKR, respectively. There was no HPD patients defined by ΔTGR. HPD patients classified by each criterion were associated with shorter median progression-free survival (PFS) according to iRECIST (TGRR ≥2, 1.6 vs 2.1 months, p<0.001; TGKR ≥2, 1.6 vs 2.1 months, p<0.001) and median overall survival (OS) than non-HPD-PD patients (TGRR ≥2, 2.4 vs 5.2 months, p=0.002; TGKR ≥2, 2.4 vs 5.2 months, p=0.002). HPD was not associated with age, sex, histology, stage, brain metastasis, nor PD-L1 expression at baseline. There was no pseudoprogression in patients classified as HPD. HPD defined by pre- and on-treatment tumor kinetics was observed in 12-15% of patients with advanced NSCLC treated with second-line ICI monotherapy, and correlated with shorter PFS and OS. TGR and TGK could classify HPD patients from non-HPD PD with similar discriminability. Further studies are needed to investigate clinical and molecular determinants that distinguish HPD from non-HPD PD and pseuoprogression.