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 tumorinfiltrating lymphocytes (TILs) and human leukocyte antigen class 1. Efficacy endpoints included objective response rate (ORR), overall survival (OS), progression-free | 1677 KATO eT Al.

Nivolumab versus chemotherapy in Japanese patients with advanced esophageal squamous cell carcinoma: a subgroup analysis of a multicenter, randomized, open-label, phase 3 trial (ATTRACTION-3)

“…Immune checkpoint inhibition is one such strategy successfully evaluated in many cancers. The efficacy and safety of nivolumab (an immune checkpoint inhibitor [ICI]) has been demonstrated in esophageal cancer, with a favorable 2-year overall survival (OS) in Japanese patients (17.2%) in the phase 2, single-arm ATTRACTION-1 trial [ 12 , 13 ] and with significant prolongation of OS [median OS, 10.9 months vs. 8.4 months; hazard ratio (HR) for death, 0.77; p = 0.019] in the global, phase 3, randomized, ATTRACTION-3 trial compared with chemotherapy [ 14 ]. A smaller proportion of patients in the nivolumab group [38/209 (18%)] experienced grade 3/4 treatment-related adverse events (TRAEs) versus those in the chemotherapy group [131/208 (63%)] in ATTRACTION-3 [ 14 ].…”

Five-year follow-up of nivolumab treatment in Japanese patients with esophageal squamous-cell carcinoma (ATTRACTION-1/ONO-4538-07)

“…This analysis in ATTRACTION-1 with a follow-up of > 5 years demonstrated that nivolumab monotherapy has long-term efficacy and safety for patients with chemotherapy-refractory or -intolerant esophageal cancer. Seven and four patients survived for 3 and 5 years, respectively, while the ORR, median OS, and median PFS remained unchanged at 2 years of follow-up [ 16 ]. No new safety signals were identified.…”

“…We previously reported 2-year follow-up results of ATTRACTION-1 [ 16 ]. Here, we report the longest follow-up data of nivolumab monotherapy for esophageal cancer for at least 5 years in ATTRACTION-1.…”

Preoperative neutrophil‐to‐lymphocyte ratio predicts the prognosis of esophageal squamous cell cancer patients undergoing minimally invasive esophagectomy after neoadjuvant chemotherapy

“…Today, there is an opportunity to administer immune checkpoint inhibitor therapy to patients with ESCC. Kato et al 31 reported that nivolumab showed continued long-term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma. Inhibitors of the immune checkpoint protein PD-1 affect the antitumor activity of T cells in that they block the binding between the PD-1 receptor and its ligands.…”