Hyperprogressive disease during PD-1 blockade in patients with advanced gastric cancer

Investigations for programmed cell death-1 (PD-1) blockade-induced hyperprogressive disease (HPD) have not been stringently conducted in patients with advanced gastric cancer (AGC). We explored the occurrence of HPD and its clinical implications in patients with AGC and treated with PD-1 inhibitors....

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Published in:European journal of cancer (1990) 2022-09, Vol.172, p.387-399
Main Authors: Kim, Chang Gon, Hong, Moonki, Jeung, Hei-Cheul, Lee, Garden, Chung, Hyun Cheol, Rha, Sun Young, Kim, Hyo Song, Lee, Choong-kun, Lee, Ji Hyun, Han, Yejeong, Kim, Jee Hung, Lee, Seo Young, Kim, Hyunki, Shin, Su-Jin, Baek, Song-Ee, Jung, Minkyu
Format: Article
Language:English
Subjects:
Advanced gastric cancer
Apoptosis
Cancer
Cell death
Confidence intervals
Failure analysis
Gastric cancer
Growth kinetics
Growth rate
Health hazards
Health services
Hyperprogressive disease
Inhibitors
Irinotecan
Kinetics
Patients
PD-1 blockade
PD-1 protein
PD-L1 protein
Pembrolizumab
Survival
Tumors
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Summary:Investigations for programmed cell death-1 (PD-1) blockade-induced hyperprogressive disease (HPD) have not been stringently conducted in patients with advanced gastric cancer (AGC). We explored the occurrence of HPD and its clinical implications in patients with AGC and treated with PD-1 inhibitors. We enrolled 169 patients with AGC and treated with either the PD-1 blockade (nivolumab or pembrolizumab; N = 112) or irinotecan monotherapy (N = 57) as a single agent. Tumour growth dynamics based on tumour growth kinetics and tumour growth rate (TGR) and time to treatment failure were analysed to define HPD. The incidence, clinical consequences and predictive markers of HPD were investigated. The optimal criteria for HPD were 4-fold increases in both tumour growth kinetics and TGR ratios and a 40% increase in TGR based on the analysis for patients treated with irinotecan. In total, 10.7% (12/112) of patients experienced HPD after PD-1 inhibitor treatment. Patients with HPD had both shorter progression-free survival (hazard ratio: 2.318; 95% confidence interval: 1.205–4.460) and overall survival (hazard ratio: 2.542; 95% confidence interval: 1.314–4.918) than patients with progressive disease without HPD, losing opportunities for subsequent systemic treatments. Although other variables including PD-L1 expression were not associated with the occurrence of HPD, hypoalbuminemia (
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2022.05.042