TY - JOUR
T1 - Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer
AU - Kato, Ken
AU - Doki, Yuichiro
AU - Ura, Takashi
AU - Hamamoto, Yasuo
AU - Kojima, Takashi
AU - Tsushima, Takahiro
AU - Hironaka, Shuichi
AU - Hara, Hiroki
AU - Kudo, Toshihiro
AU - Iwasa, Satoru
AU - Muro, Kei
AU - Yasui, Hirofumi
AU - Minashi, Keiko
AU - Yamaguchi, Kensei
AU - Ohtsu, Atsushi
AU - Kitagawa, Yuko
N1 - Funding Information:
We thank the patients and their families, and investigators and staff members participating in this study. Medical writing assistance for the preparation of the outline and first draft of this manuscript was provided by Sheridan Henness, PhD, of inScience Communications, Springer Healthcare. This assistance was funded by Ono Pharmaceuticals and Bristol‐Myers Squibb. This study was funded by Ono Pharmaceuticals and Bristol‐Myers Squibb.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - The long-term efficacy of nivolumab in esophageal squamous cell carcinoma and its association with disease biomarkers are currently not well known. Therefore, we investigated the association in Japanese patients with treatment-refractory advanced esophageal cancer who participated in an open-label, single-arm, multicenter phase II study. Patients received nivolumab 3 mg/kg i.v. every 2 weeks until disease progression or unacceptable toxicity, and were followed up for 2 years after the initial dosing of the last patient. Archival tissue samples were collected before treatment and analyzed for programmed death ligand-1 (PD-L1) and CD8+ status of tumors and tumor-infiltrating lymphocytes (TILs) and human leukocyte antigen class 1. Efficacy end-points included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to response, and duration of response. Of 65 enrolled patients (83% male), 64 were evaluable for efficacy and 41 (63%) for biomarkers. The ORR, median OS, and survival rate were 17.2%, 10.78 months, and 17.2%, respectively. Time to response was 1.45 months and duration of response was 11.17 months. The PD-L1 positivity of tumor cells was possibly associated with better PFS (2.04 vs 1.41 months, cut-off 1%) and OS (11.33 vs 6.24 months, cut-off 1%). Median OS was prolonged in patients with a median number of TILs greater than 63.75% vs 63.75% or less (11.33 vs 7.85 months). Nivolumab showed continued long-term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Further investigation of PD-L1 tumor expression and TILs as potential biomarkers for predicting patients likely to benefit from nivolumab therapy is warranted.
AB - The long-term efficacy of nivolumab in esophageal squamous cell carcinoma and its association with disease biomarkers are currently not well known. Therefore, we investigated the association in Japanese patients with treatment-refractory advanced esophageal cancer who participated in an open-label, single-arm, multicenter phase II study. Patients received nivolumab 3 mg/kg i.v. every 2 weeks until disease progression or unacceptable toxicity, and were followed up for 2 years after the initial dosing of the last patient. Archival tissue samples were collected before treatment and analyzed for programmed death ligand-1 (PD-L1) and CD8+ status of tumors and tumor-infiltrating lymphocytes (TILs) and human leukocyte antigen class 1. Efficacy end-points included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to response, and duration of response. Of 65 enrolled patients (83% male), 64 were evaluable for efficacy and 41 (63%) for biomarkers. The ORR, median OS, and survival rate were 17.2%, 10.78 months, and 17.2%, respectively. Time to response was 1.45 months and duration of response was 11.17 months. The PD-L1 positivity of tumor cells was possibly associated with better PFS (2.04 vs 1.41 months, cut-off 1%) and OS (11.33 vs 6.24 months, cut-off 1%). Median OS was prolonged in patients with a median number of TILs greater than 63.75% vs 63.75% or less (11.33 vs 7.85 months). Nivolumab showed continued long-term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Further investigation of PD-L1 tumor expression and TILs as potential biomarkers for predicting patients likely to benefit from nivolumab therapy is warranted.
KW - CD8 tumor-infiltrating lymphocyte
KW - esophageal squamous cell carcinoma
KW - long-term survival
KW - nivolumab
KW - programmed death-1
UR - http://www.scopus.com/inward/record.url?scp=85084229223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084229223&partnerID=8YFLogxK
U2 - 10.1111/cas.14380
DO - 10.1111/cas.14380
M3 - Article
C2 - 32160365
AN - SCOPUS:85084229223
VL - 111
SP - 1676
EP - 1684
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 5
ER -