Hyperprogressive disease during treatment with immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

Abstract

e21664 Background: 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 prognostic factors of HPD. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included in the analysis. The variables were compared by chi-square and Fisher test, then we performed a multivariate logistic regression model to analyse the effects of the covariates, and finally we performed a Kaplan Meier survival analysis. 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. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. Nine of 104 patients (8.7%) in our population developed HPD during treatment with ICI. HPD occured within the first two months of treatment in all 9 patients, and was associated with worse overall survival in the multivariate analysis by Cox regression (12.6 vs 2.6 months; HR 13.94, p < 0.001). The presence of 2 or more metastatic sites was related to the development of HPD in the multivariate analysis (HR 8.59, p = 0.026). Conclusions: 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.