Comparison of Different Methods for Defining Hyperprogressive Disease in NSCLC

Abstract

Introduction: Hyperprogressive disease (HPD) as a consequence of immune checkpoint inhibitors in NSCLC has been reported in multiple studies. However, inconsistent results in incidence and survival outcomes within studies, together with different assessment methods, have led to increasing controversy regarding the concept of HPD.Methods: Consecutive patients treated with nivolumab (N ¼ 42) or docetaxel (N ¼ 37) were evaluated. HPD was quantified by applying three different methods (tumor growth rate [TGR], tumor growth kinetics [TGK], and Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). HPD rates were compared between and within both cohorts using the different methods.Results: Using TGR, TGK, and RECIST 1.1, we identified seven (16.7%), seven (16.7%), and six (14.3%) patients with HPD in the nivolumab cohort and three (8.1%), four (10.8%), and five (13.6%) in the docetaxel cohort, respectively. We observed a higher concordance between TGR and TGK (90.1%) compared with RECIST 1.1 (31.3% and 37.5% with TGR and TGK, respectively). We found no significant differences in the overall survival between patients with progressive disease and HPD in either cohort.Conclusions: TGR and TGK revealed high concordance rates for identifying patients with HPD in NSCLC. The incidence of HPD was numerically higher in patients treated with immune checkpoint inhibitors. Standardization of methods for measuring HPD and its exploration in larger studies are needed to establish its clinical meaning in NSCLC.

Redefining Clinical Hyperprogression: the Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy

“…Incidences of HPD in NSCLC patients treated with ICI monotherapy have varied, increasing in the order of ΔTGR, TGR ratio, and TGK ratio as follows 5.1% (n=12), 15.6% (n=37), and 18.1% (n=43) in one study (14), and 5.7% (n=8), 11.3% (n=16), and 17.0% (n=24) in the other study (7). However, two studies reported a similar proportion of NSCLC patients with HPD based on TGR ratio and TGK ratio (TGR ratio vs. TGK ratio: 20.5% (n=54) vs 20.4% (n=55), and 16.7% (n=7) vs. 16.7% (n=7), respectively) (21, 22). Notably, the definitions of HPD varied across these studies.…”

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

“…Illustrated by Figure 8 , a significant discrepancy was found among the five subgroups ( P = .02). The pooled incidence of HPD was 16.2% in patients suffering from gastrointestinal (GI) tract cancer ( n = 5, 95% CI, 10.4%–24.1%) ( 33 , 45 , 56 , 57 , 60 ); 14.4% in patients with NSCLC ( n = 14, 95% CI, 12.2%–17.0%) ( 13 , 16 , 17 , 21 , 29 , 34 , 42 – 44 , 51 , 54 , 59 , 62 , 63 ), 9.9% in patients with melanoma ( n = 3, 95% CI, 1.6%–43.4%) ( 35 , 36 , 53 ); 10.8% in patients with HCC ( n = 4, 95% CI, 8.4%–13.8%) ( 14 , 39 , 40 , 61 ); 18.06% in patients with HNC ( n = 6, 95% CI, 15.0%–21.6%) ( 15 , 37 , 38 , 48 , 49 , 52 ). Significant differences were found between these five tumor types (Q = 11.16, P = .0248), indicating that tumor type is a source of heterogeneity.…”

“…TGK is also a common approach for HPD evaluation. To further reassure clinicians of the HPD diagnosis, some studies calculate both TGR and TGK to verify the final evaluation ( 29 , 34 , 39 , 40 ). Other criteria are also used to describe the HPD phenomenon, including “more than 40% or 50% increment of total tumor burden,” “ECOG PS exceeding 2 during anti-tumor treatment,” and “more than two new lesions exist in previously involved organ or new organs.” However, these criteria are not in consensus for the oncological community.…”

“…TGR and TGK to verify the final evaluation (29,34,39,40). Other criteria are also used to describe the HPD phenomenon, including "more than 40% or 50% increment of total tumor burden," "ECOG PS exceeding 2 during anti-tumor treatment," and "more than two new lesions exist in previously involved organ or new organs."…”

Hyperprogressive Disease in Malignant Carcinoma With Immune Checkpoint Inhibitor Use: A Review

“…The different definitions may result in a wide variation in HPD incidences. ICI-induced HPD remains controversial because of a lack of consensual definition, and HPD definitions are very heterogeneous in terms of incidence rate and clinical impact (8)(9)(10).…”