Abstract 5209: Hyperprogression in various solid cancers treated with immune checkpoint inhibitors in the real world
Authors: Kim Jwa Hoon , Lee Soohyeon , Hong Min Hee , Kim Jee Hyun , Kang Eun Joo , Kim Tae-Yong , Park Yeon Hee , Han Ji-Youn , Kim Il-Hwan , Kim Sang-We , Lee Dae Ho , Lee Jae Lyun , Lee Jae Cheol , Choi Chang-Min , Yoo Changhoon , Yoon Shinkyo , Jeong Jae Ho , Seo Seyoung , Kim Sun Young , Ahn Jin-Hee , Park Sook Ryun 
Published: June 2022

Abstract
Purpose: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer prognosis in various cancer types. However, ICIs may trigger accelerated tumor progression, regarded as hyperprogressive disease (HPD), in certain patients, and it is still challenging to define HPD. We aimed to investigate the landscape of HPD and the prognostic value of its different definitions in advanced solid cancer patients treated with ICIs.
Methods: We conducted a multicenter, prospective cohort study for solid cancer patients receiving ICIs. Among them, only unresectable or metastatic cancer patients were included in this analysis. Tumor response was evaluated according to RECIST 1.1. In patients who showed progressive disease (PD) by RECIST 1.1 at the first tumor evaluation, HPD was defined according to the following three criteria: A) tumor growth kinetics (TGK) ratio (TGKpost-ICI/TGKpre-ICI &gt;=2, B) &gt;=10mm increase in sum of target lesion (SUMtarget)and at least one of the following two criteria - 1) &gt;=40% increase in SUMtarget or 2) &gt;=20% increase in SUMtarget and the appearance of new lesions in at least two different organs, C) TGK ratio &gt;=2 and &gt;50% increase in SUMtarget. The discriminatory ability of three definitions in terms of overall survival (OS) were evaluated by the chi-square, C-statistics, and prediction error with integrated Brier score.
Results: A total of 427 patients were included; head and neck (n=22, 5.2%), lung (n=173, 40.5%), breast (n=8, 1.9%), gastrointestinal tract (n=99, 23.2%), hepatobiliary pancreas (n=57, 13.3%), genitourinary (n=56, 13.1%), melanoma (n=5, 1.2%), and others (n=7, 1.6%). Incidences of HPD were 4.9%, 14.8%, and 11.5% in definition A, B, C, respectively. The incidence of HPD was relatively low (2.7%-9.5%) in non-small cell lung cancer compared to other cancer types (10.1%-21.5% in esophagogastric cancer, 3.9%-21.6% in hepatobiliary pancreas cancer, and 5.5%-22.5% in genitourinary cancer). Median OS was the worst for patients with HPD, which ranged from 4.8 months to 4.9 months according to definition A-C. After multivariate analysis adjusting for cancer types, ICIs types, and the number of prior anti-cancer therapy, each definition remained a significant factor for OS (P&lt;0.001, respectively). Both chi-square and C-statistics of definition B were higher than those of definition A and C, although prediction error with integrated brier scores was similar between three definitions.
Conclusions: Incidences of HPD appear to be various according to its definitions and cancer types. Given that the RECIST-based definition B not requiring pre-ICI imaging, showed similar discriminatory ability to predict dismal OS compared to TGK-based ones, it may be the most feasible and convenient measure to capture HPD in daily clinical practice.
Citation Format: Jwa Hoon Kim, Soohyeon Lee, Min Hee Hong, Jee Hyun Kim, Eun Joo Kang, Tae-Yong Kim, Yeon Hee Park, Ji-Youn Han, Il-Hwan Kim, Sang-We Kim, Dae Ho Lee, Jae Lyun Lee, Jae Cheol Lee, Chang-Min Choi, Changhoon Yoo, Shinkyo Yoon, Jae Ho Jeong, Seyoung Seo, Sun Young Kim, Jin-Hee Ahn, Sook Ryun Park. Hyperprogression in various solid cancers treated with immune checkpoint inhibitors in the real world [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5209.