Isaku Okamoto1, Hiroki Sato2, Kiyoaki Tsukahara2. 1. Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: isaku@tokyo-med.ac.jp. 2. Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Abstract
OBJECTIVE: Our facility measures programmed cell death ligand 1 (PD-L1) expression in all patients before administering nivolumab. The aim of the present study is to clarify the association between overall survival (OS) and PD-L1 expression. PATIENTS AND METHODS: Subjects in this study were 52 patients with R/M-HNC cancer (45 men, 7 women) administered nivolumab in our facility between June 1, 2017 and January 31, 2019. Mean age was 62.2 years (median, 65 years; range, 28-81 years). Histopathological type was squamous cell carcinoma (SCC) in 48 cases, and non-SCC in 4 cases. We set OS as the primary endpoint and progression-free survival (PFS), overall response rate (ORR), association of OS and PD-L1 expression and association of PFS and PD-L1 expression as secondary endpoints. The cut-off for PD-L1 expression was set using the receiver operating characteristic (ROC) curve. We compared OS, PES and ORR using this PD-L1 cut-off for all patients and for the SCC group. OS and PFS were calculated using Kaplan-Meier methods. The log-rank test was used for statistical analysis, with values of p < 0.05 taken as significant. For PD-L1 immunohistochemistry assays, Dako 28-8 antibody was used. RESULTS: In the all-patients group, median OS was 9.6 months and 1-year OS rate was 40.4%. Median PFS was 4.0 months and 1-year PFS rate was 37.8%. The cut-off value of PD-L1 expression for OS was 40% for all patients and the SCC group. When PD-L1 expression was ≥40%, OS was significantly better in both all patients and the SCC group (p = 0.004, 0.007). The cut-off value of PD-L1 expression for PFS was also 40%. When PD-L1 expression was ≥40%, PFS was better in all patients and the SCC group (P = 0.003, 0.009). In the all-patients group, ORR was 19.2% and disease control rate (DCR) was 44.2%. When PD-L1 expression was ≥40%, ORR was 44.4% and DCR 83.3%. CONCLUSION: In the present study, when PD-L1 expression was high (≥40%), OS was significantly better (p = 0.004). This finding has not been reported in other research on R/M-HNC. PFS and ORR were also better with high PD-L1 expression. Regarding patterns of progression with a PD-L1 expression cut-off of 40%, hyperprogression was significantly more frequent for PD-L1 expression <40% (p = 0.039). Therefore, high PD-L1 expression could offer a predictor of prognosis and efficacy for nivolumab. The present findings may prove useful in considering treatment strategies.
OBJECTIVE: Our facility measures programmed cell death ligand 1 (PD-L1) expression in all patients before administering nivolumab. The aim of the present study is to clarify the association between overall survival (OS) and PD-L1 expression. PATIENTS AND METHODS: Subjects in this study were 52 patients with R/M-HNC cancer (45 men, 7 women) administered nivolumab in our facility between June 1, 2017 and January 31, 2019. Mean age was 62.2 years (median, 65 years; range, 28-81 years). Histopathological type was squamous cell carcinoma (SCC) in 48 cases, and non-SCC in 4 cases. We set OS as the primary endpoint and progression-free survival (PFS), overall response rate (ORR), association of OS and PD-L1 expression and association of PFS and PD-L1 expression as secondary endpoints. The cut-off for PD-L1 expression was set using the receiver operating characteristic (ROC) curve. We compared OS, PES and ORR using this PD-L1 cut-off for all patients and for the SCC group. OS and PFS were calculated using Kaplan-Meier methods. The log-rank test was used for statistical analysis, with values of p < 0.05 taken as significant. For PD-L1 immunohistochemistry assays, Dako 28-8 antibody was used. RESULTS: In the all-patients group, median OS was 9.6 months and 1-year OS rate was 40.4%. Median PFS was 4.0 months and 1-year PFS rate was 37.8%. The cut-off value of PD-L1 expression for OS was 40% for all patients and the SCC group. When PD-L1 expression was ≥40%, OS was significantly better in both all patients and the SCC group (p = 0.004, 0.007). The cut-off value of PD-L1 expression for PFS was also 40%. When PD-L1 expression was ≥40%, PFS was better in all patients and the SCC group (P = 0.003, 0.009). In the all-patients group, ORR was 19.2% and disease control rate (DCR) was 44.2%. When PD-L1 expression was ≥40%, ORR was 44.4% and DCR 83.3%. CONCLUSION: In the present study, when PD-L1 expression was high (≥40%), OS was significantly better (p = 0.004). This finding has not been reported in other research on R/M-HNC. PFS and ORR were also better with high PD-L1 expression. Regarding patterns of progression with a PD-L1 expression cut-off of 40%, hyperprogression was significantly more frequent for PD-L1 expression <40% (p = 0.039). Therefore, high PD-L1 expression could offer a predictor of prognosis and efficacy for nivolumab. The present findings may prove useful in considering treatment strategies.
Keywords:
Nivolumab; Overall response rate; Overall survival; Programmed cell death ligand 1; Progression-free survival; Recurrent or metastatic head and neck cancer