Nivolumab for the treatment of esophageal cancer

ABSTRACT

Introduction: Esophageal cancer (EC) is the seventh most common cancer and the sixth leading cause of cancer death worldwide. The prognosis for advanced EC patients remains poor and there are few effective therapeutic agents available. Nivolumab is a fully human IgG4 monoclonal antibody that exerts antitumor activity by inhibiting the interaction of programmed cell death protein 1 on activated lymphocytes with its ligands. Nivolumab monotherapy showed significant benefit for overall survival of patients with advanced esophageal squamous cell carcinoma (ESCC) relative to taxane as a second-line treatment. Additionally, adjuvant nivolumab monotherapy showed significant disease-free survival benefit relative to placebo for resectable EC patients with residual pathologic disease who had received neoadjuvant chemoradiotherapy followed by surgery.

Areas covered: Here, we provide an overview of checkpoint blockade with nivolumab and present the available clinical data related to its use in EC.

Expert opinion: Nivolumab should be the standard second-line treatment for advanced ESCC patients and possibly adjuvant treatment of choice after neoadjuvant chemoradiotherapy followed by surgery. Trials assessing efficacy of a combination of cytotoxic agents and nivolumab as first-line treatment, nivolumab-containing chemoradiotherapy, and neoadjuvant chemotherapy are ongoing. These trials should result in improved protocols for better clinical outcomes in EC.

KEYWORDS:

• Esophageal adenocarcinoma (EAC)
• esophageal carcinoma (EC)
• esophageal squamous cell carcinoma (ESCC)
• immune checkpoint inhibitor
• nivolumab
• programmed death ligand-1 (PD-L1)

Article highlights

• The prognosis of advanced esophageal cancer patients remains poor and there are few effective therapeutic agents.

• Nivolumab is a fully human IgG4 monoclonal antibody that targets programmed cell death protein 1.

• Based on the ATTRACTION-3 phase III trial, nivolumab monotherapy was approved by the FDA on 10 June 2020, as a treatment for unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma patients who experienced disease progression after prior fluoropyrimidine- and platinum-based systemic chemotherapy.

• The CheckMate-577 phase III trial showed the superiority of adjuvant nivolumab monotherapy compared to placebo for resectable EC or esophagogastric junction cancer in patients who had received neoadjuvant chemoradiation but failed to achieve a pathologic complete response.

• Nivolumab-containing investigational treatments are being evaluated.

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Declaration of interest

S Yamamoto has honoraria from ONO Pharmaceuticals and Bristol-Myers Squibb. K Kato has received research funds from ONO, BMS, MSD, Beigeen, Shionogi, and Oncolys Biopharma, honoraria from ONO, Eli Lilly, Taiho. The author(s) have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.