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

 Chang Gon Kim  ;  Moonki Hong  ;  Hei-Cheul Jeung  ;  Garden Lee  ;  Hyun Cheol Chung  ;  Sun Young Rha  ;  Hyo Song Kim  ;  Choong-Kun Lee  ;  Ji Hyun Lee  ;  Yejeong Han  ;  Jee Hung Kim  ;  Seo Young Lee  ;  Hyunki Kim  ;  Su-Jin Shin  ;  Song-Ee Baek  ;  Minkyu Jung 
 EUROPEAN JOURNAL OF CANCER, Vol.172 : 387-399, 2022-09 
Journal Title
Issue Date
Disease Progression ; Humans ; Hypoalbuminemia* ; Immune Checkpoint Inhibitors / adverse effects ; Irinotecan / adverse effects ; Programmed Cell Death 1 Receptor ; Stomach Neoplasms* / drug therapy
Advanced gastric cancer ; Hyperprogressive disease ; PD-1 blockade
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.
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Appears in Collections:
6. Others (기타) > Palliative Care Center (완화의료센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jee Hung(김지형) ORCID logo https://orcid.org/0000-0002-9044-8540
Kim, Chan(김찬)
Kim, Chang Gon(김창곤)
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Baek, Song Ee(백송이) ORCID logo https://orcid.org/0000-0001-8146-2570
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Lee, Seoyoung(이서영)
Lee, Jee Hyun(이지현)
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
Hong, Moonki(홍문기) ORCID logo https://orcid.org/0000-0001-9528-4912
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