Abstract 974P
Background
Immunotherapy (IO) has emerged as a powerful treatment option in many advanced cancers. An alarming response phenotype termed hyperprogressive disease (HPD) has been described, in which tumors exhibit rapid growth upon initiation of IO. HPD has been linked to adverse clinical outcomes, however, the mechanisms that underlie HPD remain poorly understood.
Methods
Patients treated between 1/2013 and 5/2019 at the University of Cincinnati that had complete Caris Life Sciences molecular profiling were included. Baseline clinical characteristics and treatment history were extracted from the medical record. All solid tumor types were included. Patients with incomplete treatment or imaging data, or no RECIST measurable disease were excluded. Target lesions were recorded according to RECIST 1.1. HPD was defined as doubling of the tumor growth rate (TGR) after initiation of IO. Time-to-treatment-failure (TTF) was defined as time from IO initiation to clinical or radiologic progression, death, toxicity or new treatment start. Clinical characteristics and genomic profiles of HPD and non-HPD groups were compared using student’s t-test, chi-squared test, and Fisher’s exact test. 136 patients were evaluated. 34 patients had the requisite scans and measurable disease to qualify for TGR calculation.
Results
We identified 7/32 (22%) patients who met criteria for HPD. HPD was associated with older age at diagnosis (63.5 vs 59.3), decreased overall survival (3.8 vs 5.5 months), and shorter TTF (7.8 vs 10.1 months), although not statistically significant. Molecular profiles of HPD and non-HPD patients showed similar frequency of mutations in TMB, TP53, EGFR, RTK co-factors and DDR pathways. TTF<3 months was correlated with more frequent EGFR, and NOTCH mutations. TTF>3 months was associated with mutations in DDR and WNT pathways.
Conclusions
There were no statistically significant clinical or genomic differences between HPD and non-HPD patients. TTF analysis identified EGFR, NOTCH, DDR and WNT pathways as possible predictors of response to IO. This study is limited by small sample size, but may support the hypothesis that HPD represents the natural disease course of some patients with aggressive cancers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.E. McGrath: Financial Interests, Institutional, Full or part-time Employment: Caris Life Sciences. T. Wise-Draper: Financial Interests, Personal, Advisory Board: Exicure; Financial Interests, Personal, Invited Speaker: Physician Education Resource; Financial Interests, Personal, Advisory Board: Rakuten Medical; Other, Personal, Other, Consultant: Shattuck Labs; Financial Interests, Personal, Ownership Interest: High Enroll; Financial Interests, Personal and Institutional, Principal Investigator: Alkermes; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal and Institutional, Principal Investigator: BMS; Financial Interests, Personal and Institutional, Principal Investigator: Boston Medical; Financial Interests, Personal and Institutional, Principal Investigator: Debio Pharm; Financial Interests, Personal and Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal and Institutional, Principal Investigator: EMD Serono; Financial Interests, Personal and Institutional, Principal Investigator: Epizyme; Financial Interests, Personal and Institutional, Principal Investigator: Exicure; Financial Interests, Personal and Institutional, Principal Investigator: Iovance; Financial Interests, Personal, Research Grant: Merck & Co.; Financial Interests, Personal and Institutional, Principal Investigator: Replimune; Financial Interests, Personal and Institutional, Principal Investigator: Shattuck Labs; Financial Interests, Personal, Research Grant: Tesaro/GSK. All other authors have declared no conflicts of interest.