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Article

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

1
Section of Medical Oncology, Second Department of Internal Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
2
Second Department of Medical Oncology, Agios Savas Anticancer Hospital, 11522 Athens, Greece
3
Second Department of Pathology, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
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Department of Otolaryngology-Head and Neck Surgery, Hippokration General Hospital, University of Athens, 11527 Athens, Greece
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Oral Medicine Clinics, A. Syggros Hospital of Dermatologic and Venereal Diseases, Department of Dermatology, School of Medicine, University of Athens, 16121 Athens, Greece
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Department of Otorhinolaryngology, Facial Plastic and Reconstructive Surgery, Städtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany
7
Second Otolaryngology Department, Attikon University Hospital, 12462 Athens, Greece
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(2), 286; https://doi.org/10.3390/cancers13020286
Received: 15 December 2020 / Revised: 30 December 2020 / Accepted: 6 January 2021 / Published: 14 January 2021
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.
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. View Full-Text
Keywords: hyperprogression; head and neck cancer; immunotherapy; TGK hyperprogression; head and neck cancer; immunotherapy; TGK
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MDPI and ACS Style

Economopoulou, P.; Anastasiou, M.; Papaxoinis, G.; Spathas, N.; Spathis, A.; Oikonomopoulos, N.; Kotsantis, I.; Tsavaris, O.; Gkotzamanidou, M.; Gavrielatou, N.; Vagia, E.; Kyrodimos, E.; Gagari, E.; Giotakis, E.; Delides, A.; Psyrri, A. Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC). Cancers 2021, 13, 286. https://doi.org/10.3390/cancers13020286

AMA Style

Economopoulou P, Anastasiou M, Papaxoinis G, Spathas N, Spathis A, Oikonomopoulos N, Kotsantis I, Tsavaris O, Gkotzamanidou M, Gavrielatou N, Vagia E, Kyrodimos E, Gagari E, Giotakis E, Delides A, Psyrri A. Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC). Cancers. 2021; 13(2):286. https://doi.org/10.3390/cancers13020286

Chicago/Turabian Style

Economopoulou, Panagiota, Maria Anastasiou, George Papaxoinis, Nikolaos Spathas, Aris Spathis, Nikolaos Oikonomopoulos, Ioannis Kotsantis, Onoufrios Tsavaris, Maria Gkotzamanidou, Niki Gavrielatou, Elena Vagia, Efthymios Kyrodimos, Eleni Gagari, Evangelos Giotakis, Alexander Delides, and Amanda Psyrri. 2021. "Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)" Cancers 13, no. 2: 286. https://doi.org/10.3390/cancers13020286

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