Hyperprogressive disease (HPD) is a new pattern of progressión during immunotherapy and is described as an acceleration of tumor growth during treatment with immune checkpoint inhibitors (ICI). The rate of HPD in advanced solid tumors remains unknown, but it has been reported in 9% to 29% of patients in two recent series. Our aim was to study possible prognostic factors related to HPD.
We collected data of 66 patients diagnosed with advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and May 2019. Several variables as clinical, tumour-related and therapeutical were included and univariate and multivariate Cox regression analysis were performed. We described HPD as disease progression at first evaluation with an increase in tumor growth rate exceeding 50%, according to Gustave Roussy criteria previously reported.
Cohort of 50 men and 16 women, median age of 67 years and 80% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 66% were active or ex-smokers and 34% had never smoked. 62% of patients had adenocarcinoma histology, 32% scamous and 3% had not otherwise specified (NOS) carcinoma histology. 30 of the 66 patients (45%) had 2 or more metastatic sites. 53% of patients had unknown PDL1 status; 9% had no PDL1 expression, 9% low expression and 27% high expression. 82% of patients had progressed to prior line of treatment, while 18% were treatment-naive. Seven of 66 patients (10.6%) in our population developed HPD during treatment with ICI. HPD occured within the first two months of treatment in all 7 patients, and was associated with worse overall survival in the multivariate regression Cox analysis (43.6 vs 11.3 months; HR 4.35, p = 0.0037). The presence of 2 or more metastatic sites was related to the development of HPD in the multivariate analysis (HR 6.74, p = 0.009).
The incidence of HPD in our population is concordant with previous report about this topic. As previously described by Ferrara et al, HPD was significantly associated with a high number of metastatic sites before start treatment with ICI and correlated with poor outcomes in patients with advanced NSCLC.
The authors.
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All authors have declared no conflicts of interest.