Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer.

Abstract

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.

• Authors: Ken Kato, Yuichiro Doki, Takashi Ura, Yasuo Hamamoto, Takashi Kojima, Takahiro Tsushima, Shuichi Hironaka, Hiroki Hara, Toshihiro Kudo, Satoru Iwasa, Kei Muro, Hirofumi Yasui, Keiko Minashi, Kensei Yamaguchi, Atsushi Ohtsu, Yuko Kitagawa
• Journal: Cancer science (Cancer Sci) Vol. 111 Issue 5 Pg. 1676-1684 (May 2020) ISSN: 1349-7006 [Electronic] England
• PMID: 32160365 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• CD8 Antigens
• Histocompatibility Antigens Class I
• Nivolumab

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents, Immunological (administration & dosage, therapeutic use)
• B7-H1 Antigen (metabolism)
• Biomarkers, Tumor (metabolism)
• CD8 Antigens (metabolism)
• Drug Resistance, Neoplasm
• Esophageal Neoplasms (drug therapy, mortality, pathology)
• Esophageal Squamous Cell Carcinoma (drug therapy, mortality, pathology)
• Female
• Follow-Up Studies
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Japan
• Lymphocytes, Tumor-Infiltrating (metabolism)
• Male
• Middle Aged
• Nivolumab (administration & dosage, therapeutic use)
• Survival Rate
• Treatment Outcome
• Tumor Burden (drug effects)