Panagiota Economopoulou1, Maria Anastasiou1, George Papaxoinis2, Nikolaos Spathas1, Aris Spathis3, Nikolaos Oikonomopoulos3, Ioannis Kotsantis1, Onoufrios Tsavaris1, Maria Gkotzamanidou1, Niki Gavrielatou1, Elena Vagia1, Efthymios Kyrodimos4, Eleni Gagari5, Evangelos Giotakis6, Alexander Delides7, Amanda Psyrri1. 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. 4. Department of Otolaryngology-Head and Neck Surgery, Hippokration General Hospital, University of Athens, 11527 Athens, Greece. 5. Oral Medicine Clinics, A. Syggros Hospital of Dermatologic and Venereal Diseases, Department of Dermatology, School of Medicine, University of Athens, 16121 Athens, Greece. 6. Department of Otorhinolaryngology, Facial Plastic and Reconstructive Surgery, Städtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany. 7. Second Otolaryngology Department, Attikon University Hospital, 12462 Athens, Greece.
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.
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 HPDpatients. EGFR gene amplification was only observed in HPDpatients, 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.
Entities:
Keywords:
TGK; head and neck cancer; hyperprogression; immunotherapy
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