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.
| Original language | English |
|---|---|
| Pages (from-to) | 387-399 |
| Number of pages | 13 |
| Journal | European Journal of Cancer |
| Volume | 172 |
| DOIs | |
| Publication status | Published - 2022 Sept |
Bibliographical note
Funding Information:This work was supported by the National Research Foundation of Korea by the Korean government ( 2021R1I1A1A01059271 to C.G.K., 2021R1A2C2009400 to M.J.), Research Grant by Korean Society of Medical Oncology (to M.J.), Young Medical Scientist Research Grant Program funded by Daewoong Foundation (DY20206P to C.G.K.), and Internal Medicine Research Grant funded by Yonsei University College of Medicine ( 4323130 to M.H.).
Funding Information:
This work was supported by the National Research Foundation of Korea by the Korean government (2021R1I1A1A01059271 to C.G.K., 2021R1A2C2009400 to M.J.), Research Grant by Korean Society of Medical Oncology (to M.J.), Young Medical Scientist Research Grant Program funded by Daewoong Foundation (DY20206P to C.G.K.), and Internal Medicine Research Grant funded by Yonsei University College of Medicine (4323130 to M.H.).The authors thank all patients who contributed to this study. We also express our sincere thanks to Yun Jin Choi, Jin Young Oh, and Ha Na Kwon (Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea) for acquiring the data and Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for artistic support related to this work. We thank all the patients who participated in this study.
Publisher Copyright:
© 2022 Elsevier Ltd
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
