Abstract
Background Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7); P < 0.01). Factors related to HPD include more than 2 metastatic sites, ECOG performance status ≥ 2, hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors' analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.
Highlights
The interaction between the human immune system and tumor growth has been a hot topic in recent years
In order to avoid the potential risks during the treatment with progressive disease (PD)-1/PD-L1 inhibitors, it is necessary to actively explore the clinicopathological features and biomarkers related to the occurrence of hyperprogressive disease (HPD)
A total of 698 patients with the treatment of PD-1 inhibitors from January 2015 to January 2019 from the PLA General Hospital were included in the initial database
Summary
The interaction between the human immune system and tumor growth has been a hot topic in recent years. Tumor progression was accelerated for some patients after treatment with PD-1/PD-L1 inhibitors This new pattern of progression is called hyperprogressive disease (HPD), and the rates range from 4% to 29% [10]. In order to avoid the potential risks during the treatment with PD-1/PD-L1 inhibitors, it is necessary to actively explore the clinicopathological features and biomarkers related to the occurrence of HPD. During the immunotherapy in a few patients, a flare-up of tumor growth occurred This new pattern of progression is called hyperprogressive disease (HPD). Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Especially CA199, might be served as early predictors of HPD
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