Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria

Abstract

Purpose: Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon. Experimental Design: We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response. Results: Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1-treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97-6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53-10.12; HR ¼ 1.73, 95% CI, 1.05-2.85; P ¼ 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07-6.33) and non-HPD progressors (n ¼ 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88-8.67) were not statistically significant (HR 1.4, 95% IC, 0.70-2.77; P ¼ 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs. Conclusions: HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice.

Clinical characteristics of hyperprogressive disease in NSCLC after treatment with immune checkpoint inhibitor: a systematic review and meta-analysis

“…A recent study, which included multiple cancer types, had reported that HPD measured by TGR was not associated with OS. Instead, HPD evaluated by RECIST had an impact on survival [ 18 ]. It remains to be clarified which definition of HPD would be better to separate this group of patients.…”

The biomarkers of hyperprogressive disease in PD-1/PD-L1 blockage therapy

“…Four percent (6/ 155) of 155 patients with many types of tumors had HPD, which was defined as tumor growth > 40% and a TTF ≤ 2 months. Matos et al [16] observed HPD in 15% of 214 (32/214) patients in phase I studies treated with ICI therapy, the standard of which was based on RECIST (tumor volume enlargement > 40% and a TTF ≤ 2 months) ( Table 1).…”

Combination Strategies for Immune-Checkpoint Blockade and Response Prediction by Artificial Intelligence

“…Prediction of clinical benefit by intratumoral heterogeneity (radiomic feature) and by number of disease sites [199] Ligero et al solid tumors ↑ ORR prediction by clinical-radiomics signature score [200] Tunali et al On the one hand, a subset of advanced cancer patients derives long-term survival from immune-checkpoint blockade, on the other hand, up to nine per cent of patients experience hyperprogressive disease with rapid fatal outcome upon initiation of anti-PD-1/anti-PD-L1 therapy [203]. In a clinical-radiomic approach Tunali et al were able to identify patients with a time to progression < 2 months or hyperprogressive disease within an advanced NSCLC cohort treated with single agent or double agent immunotherapy [200].…”