Background Hyperprogressive disease (HPD) is the acceleration of tumor growth observed in patients treated with immunotherapy. HPD was seen to be negatively associated with the overall survival (OS) and progression-free survival (PFS) when compared to patients without HPD.1–5 Various definitions of HPD have been used to evaluate the relationship between HPD and OS/PFS.2,6–11 This study uses two HPD definitions from Champiat and Saada-Bouzid et al. to evaluate the association between HPD and OS/PFS in lung cancer patients.8,11
Methods This study retrospectively analyzed 128 patients (N=128) and 144 regimens (N=144) at a large metropolitan academic medical center. The overall survival (OS) and progression free survival (PFS) were analyzed using cox regression to produce a hazard ratio. Clinicopathologic variables were controlled for.
Results Among the 128 patients that were analyzed in this study, immunotherapy was used as the first line in 27% (N=34) and second line in 51% (N=65) of them. Immunotherapy was also used as a single agent in 77% (N=111) of all 144 regimens. In a survival analysis, the presence of hyperprogression was strongly negatively associated with PFS and OS in both definitions (figure 1.) Using the Champiat et al. definition, patients with HPD were about 20 times more likely to show future progression [Hazard ratio (HR) 22.30; 95% confidence interval (Cl) 7.84-63.42, p<0.001]. Also, OS was greater in patients without hyperprogression [HR 2.69; 95% CI 1.11-6.5, p=0.029, table 1]. This trend was also seen with the Saada-Bouzid et al. definition, revealing a higher risk of future progression [HR 4.46; 95% CI 1.78-11.18, p<0.001] and death [HR 3.17, 95% CI 1.61-6.2, p<0.001] among patients with HPD (table 2). According to the Champiat et al. definition, patients who were female or had Eastern cooperative oncology group scale of performance status (ECOG PS) 3-4 were more likely to experience future disease progression. The Saada-Bouzid et al. definition showed that patients who were female, ECOG PS 3-4, or had immunotherapy as third line treatment or beyond resulted in a higher chance of future disease progression.
Conclusions Both definitions of HPD were associated with worse OS and PFS in lung cancer patients even after adjusting for confounding variables. Given its clinical importance associated with the poorer prognosis of patients, further attention and efforts are needed to identify hyperprogression and prevent its detrimental effects. Further studies with larger cohorts are warranted.
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