Predictive factors for hyperprogressive disease during nivolumab as anti-PD1 treatment in patients with advanced gastric cancer

Abstract

Background Hyperprogressive disease (HPD) during treatment with anti-programmed death-1/programmed death-ligand 1 monoclonal antibodies has anecdotally been reported in some types of cancers, but is not well-characterized in patients with advanced gastric cancer (AGC). Methods Total 62 AGC patients treated with nivolumab in a single institution from September 2017 to April 2018 were enrolled in this study. Tumor responses were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1, and HPD was defined as ≥ two fold increase in tumor growth rate. Clinicopathological and molecular characteristics associated with HPD were also investigated. Results Thirteen of 62 patients (21%) developed HPD after nivolumab treatment. Overall survival (OS) and progression-free survival (PFS) were significantly shorter in patients with HPD than in patients without HPD (median OS: 2.3 months vs. not reached, P < 0.001; median PFS: 0.7 months vs. 2.4 months, P < 0.001). Liver metastases (77% vs. 41%), Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2 (77% vs. 29%), and a large sum of target lesion diameters at baseline (median 104.2 mm vs. 44.9 mm) were significantly associated with HPD. Absolute neutrophil count (ANC) and C-reactive protein (CRP) level significantly increased in the first 4 weeks in only patients with HPD. Conclusions HPD was observed in AGC patients treated with nivolumab and correlated with some clinicopathological characteristics. Elevations in ANC and CRP levels upon treatment might indicate HPD.

Spondin 2 promotes the proliferation, migration and invasion of gastric cancer cells

“…We performed enhanced computed tomography (CT) of the abdomen to determine the efficacy of three complete cycles of chemotherapy. The objective response rate of patients who underwent neoadjuvant chemotherapy and conversion therapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) as follows: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) . Serum samples from 25 healthy volunteers, 20 patients with atrophic gastritis and 20 patients with gastric stromal tumours were provided during the course of the study.…”

Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

“…Hyperprogressive disease refers to a remarkably accelerated tumor growth rate (TGR) that leads to poor prognosis in patients under ICB therapy particularly anti‐PD‐1/PD‐L1 agents . Currently, no consensus has been reached on the definition of HPD .…”

“…For instance, Champiat et al first reported HPD as a RECIST 1.1 progression before ICB therapy and a twofold or greater increase in TGR during immunotherapy, whereas Ferrar et al defined HPD as a disease progression at the first evaluation with at least an increase of 50% ΔTGR (the variation of TGR before and on treatment) (Figure ) . The incidence of HPD was reported to range from 7% to 29% across different types of carcinoma . However, the discordance in the definition of HPD across published literatures challenges the direct comparison of data.…”

“…Another multicenter study including 406 NSCLC patients by Ferrar et al, the largest research investigating HPD to date, revealed that HPD was associated with poor prognosis and higher metastatic burden before treatment (>2 metastatic sites) . Other factors have also been reported to be correlated with HPD, including locoregional recurrence, liver metastases, ECOG performance status (PS) of 1 or 2, a larger sum of diameters of target lesions at baseline, and elevation in absolute neutrophil count (ANC) and C‐reactive protein (CRP) levels in the first 4 weeks . However, further efforts are required to validate these findings and figure out the underlying mechanisms of HPD.…”

“…Hyperprogressive disease refers to a remarkably accelerated tumor growth rate (TGR) that leads to poor prognosis in patients under ICB therapy particularly anti-PD-1/PD-L1 agents. 24,25,[30][31][32] Currently, no consensus has been reached on the definition of HPD. 24 For instance, Champiat et al first reported HPD as a RECIST 1.1 progression before ICB therapy and a twofold or greater increase in TGR during immunotherapy, 30 whereas Ferrar et al defined HPD as a disease progression at the first evaluation with at least an increase of 50% ΔTGR (the variation of TGR before and on treatment) ( Figure 3).…”