Hyperprogressive disease (HPD) in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI).

person Salvatore Alfieri Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Salvatore Alfieri, Roberto Ferrara, Giuseppina Calareso, Stefano Cavalieri, Francesca Platini, Moela Mancinelli, Carlo Resteghini, Ester Orlandi, Nicola Alessandro Iacovelli, Letizia Ferella, Cesare Piazza, Giulia Apollonio, Donata Galbiati, Paolo Bossi, Cristiana Bergamini, Laura Deborah Locati, Lisa F. Licitra

Authors person Salvatore Alfieri Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy info_outline Salvatore Alfieri, Roberto Ferrara, Giuseppina Calareso, Stefano Cavalieri, Francesca Platini, Moela Mancinelli, Carlo Resteghini, Ester Orlandi, Nicola Alessandro Iacovelli, Letizia Ferella, Cesare Piazza, Giulia Apollonio, Donata Galbiati, Paolo Bossi, Cristiana Bergamini, Laura Deborah Locati, Lisa F. Licitra Organizations Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Medical Oncology 1 Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Radiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Head and Neck Cancer Medical Oncology 3 Unit, Fondazione Istituto Nazionale dei Tumori, Milan, Italy, Head and Neck Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Radiotherapy 2 Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, Radiotherapy Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Department of Otorhinolaryngology and Head Neck Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy Abstract Disclosures Research Funding Other Background: HPD was described in 9% of cancer patients (pts) treated in phase I trials, in 13.8% of advanced non-small cell lung cancer and 29% of 34 HNSCC pts upon ICI. A better definition of the hallmarks and survival outcomes of HPD pts in a larger cohort of HNSCC is still lacking. Methods: We retrospectively analyzed all advanced HNSCC pts treated with ICI at our Institution between October 2014 and December 2018. Three scans, performed before ICI, at baseline and at first evaluation during ICI, were assessed according to RECIST 1.1. Tumor Growth Kinetics (TGK) pre- (TGKpre) and post-baseline (TGKpost) were measured as previously reported (Saâda-Bouzid E, Ann Oncol 2017). Pts were defined HPD if they had progression at first radiological evaluation and TGKpost/TGKpre ≥2. Correlation between HPD and clinical characteristics was performed by Fisher or t-student test. Median overall survival (mOS) and progression free survival (mPFS) were estimated using the Kaplan-Meier method and compared between HPD and non-HPD using the log-rank test. Results: Ninety pts were eligible: 18% were female, 4% had ECOG PS ≥ 2, 73% smoking history, 37% oropharyngeal cancer (61% HPV+), 65% locoregional disease (89% previously irradiated), 54% received combined immunotherapy, 75% in ≥ 2nd line. Two out of 90 pts had TGKpre = 0 and were not evaluable for TGK ratio. HPD was observed in 7.9% (7/88) of pts. HPD pts were significantly younger compared to non-HPD pts (median age 53 ± 3.7 vs 63.3 ± 0.9 years, p = 0.002) and had a significantly higher median neutrophil-lymphocyte ratio (NLR) (11.5 ± 3.5 vs 6.4 ± 0.4, p = 0.004). Overall, mOS and mPFS were 7.5 (95% CI: 4.2-10.8) and 2.2 months (95% CI: 0.9-3.4), respectively. At a median follow-up of 20.9 months (95% CI: 19-22.8), HPD pts had a significantly worse mPFS compared to non-HPD pts [1.8 (95% CI: 1.5-2.2) vs 3.5 (95% CI: 2.2-4.8) months; p = 0.001]. HPD correlated with a not significant trend in lower mOS compared to non-HPD group [3.7 (95% CI: 2.4-5.1) vs 8.3 (95% CI: 4.1-12.5) months; p = 0.348]. Three (43%) out of 7 HPD pts early switched to chemotherapy after PD to ICI having a mOS of 8.1 months (range 3.7-25.3). Excluding these 3 pts, HPD correlated with a significantly worse mOS compared to non-HPD [2.6 (95% CI: 1.9-3.3) vs 8.3 (95% CI: 4.1-12.5) months; p = 0.006]. Conclusions: HPD was identified in 7.9% of HNSCC and correlated with younger age and higher NLR. HPD pts who did not receive a subsequent treatment had poorer mPFS and mOS. The assessment of HPD in a control cohort of advanced HNSCC upon standard chemotherapy is ongoing.