Hyperprogressive disease during PD-1 blockade in patients with advanced gastric cancer. (September 2022)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of cancer. Volume 172(2022)
• Page Start: 387
• Page End: 399
• Publication Date: 2022-09
• Subjects: Advanced gastric cancer -- Hyperprogressive disease -- PD-1 blockade; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.05.042
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: 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. Methods: 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. Results: 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 (<3.25 mg/dL) at baseline was significantly associated with the occurrence of HPD ( P < 0.001) and inferior survival outcomes. Conclusions: HPD occurs in a proportion of patients with AGC and treated with PD-1 inhibitors. PD-1 inhibitor-induced HPD is associated with worse outcome, loss of eligibility for subsequent treatment and hypoalbuminemia, warranting further investigation. Graphical abstract: Image 1 Highlights: Hyperprogressive disease (HPD) occurs in 10.7% of patients with advanced gastric cancer and treated with programmed cell death inhibitors. HPD is associated with worse progression-free survival and overall survival. HPD leads to the loss of opportunity for subsequent treatments. Hypoalbuminemia is associated with the occurrence of HPD and inferior survival rate.