Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

SIMPLE SUMMARY: Immunotherapy agents, such as immune checkpoint inhibitors (ICIs), act through different mechanisms compared to conventional chemotherapy and are characterized by unique patterns of response, such as hyperprogression (HPD), which refers to the paradoxical acceleration of tumor growth kinetics (TGK). In this regard, we sought to compare patterns of response to ICIs with respect to clinical and genomic features in a cohort of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). In our cohort, HPD was observed in 15.4% of patients. We report for the first time an association of HPD with both shorter progression free survival and overall survival in HNSCC. Importantly, in a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor for survival. Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis. Genomic profiling revealed that gene amplification was more common in HPD patients. ABSTRACT: Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03–2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78–7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0–13.39) vs. 15 months in patients with non HPD (95% CI, 7.1–22.8), p = 0.0018). In a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor (p = 0.049). Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis (p = 0.028 and p = 0.012, respectively). Genomic profiling revealed that gene amplification was more common in HPD patients. EGFR gene amplification was only observed in HPD patients, but the number of events was inadequate for the analysis to reach statistical significance. The previously described MDM2 amplification was not identified. Conclusions: HPD was observed in 15.4 % of patients with R/M HNSCC treated with IO and was associated with worse PFS and OS. EGFR amplification was identified in patients with HPD.