Inhibitors of programmed death receptor 1 (PD-1) are associated with significant improvements in overall survival (OS) and durable responses in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). However, a retrospective analysis from four French centers found that approximately one third of patients with recurrent and/or metastatic SCCHN treated with PD-1/PD-L1 inhibitors experienced hyperprogression, characterized by at least doubling of tumor growth kinetics (TGK), that correlated with shorter progression-free survival (PFS).
This study retrospectively compared TGK on immunotherapy and on last treatment in 34 patients with SCCHN treated with PD-1/PD-L1 inhibitors. Ten patients (29%) treated with PD-1/PD-L1 inhibitors experienced hyperprogression. Patients with locoregional recurrence experienced hyperprogression more frequently than patients with exclusively distant metastases (39% vs 9%). There was a significant correlation between regional recurrence and hyperprogression (90% vs 37%; P = .008). Presence of metastatic cervical nodes at diagnosis was also correlated with increased risk of hyperprogression (42% vs 26%), but this did not reach statistical significance.
PFS was significantly shorter in patients experiencing hyperprogression by both RECIST (2.5 months vs 3.5 months, P = .003) and immune-related (ir)RECIST (2.9 months vs 5.1 months, P = .02) criteria. Hyperprogression was associated with a two-month decrease in OS (6.1 months vs 8.1 months), but this was not statistically significant (P = .77).
In their conclusion, the authors acknowledged the limitations of an uncontrolled, retrospective study, but indicated that this analysis lays the groundwork for future examination of hyperprogression in SCCHN and other tumors and showed the need to identify predictors of which patients might be more susceptible to hyperprogression. They indicated that continuing immunotherapy beyond progression should be avoided if patients do not experience clear clinical improvement during treatment, and that biopsies at the time of progression may help identify the mechanism of underlying hyperprogression.