Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies

ABSTRACT

Introduction: Over the last decade, epidermal growth factor receptor (EGFR) signaling was investigated as a potential target for tyrosine kinase inhibitors in the treatment of non-small-cell lung cancer (NSCLC). Necitumumab is a fully humanized IgG1 monoclonal antibody directed against the binding domain of EGFR, approved in combination with cisplatin–gemcitabine for the first-line treatment of squamous NSCLC.

Areas covered: The purpose of this manuscript is to systematically review the state of the art of necitumumab for the treatment of metastatic NSCLC, focusing on predictive factors, cost-effectiveness, and future potential combinations with additional agents.

Expert opinion: Despite recent therapeutic advances, platinum-based chemotherapy still represents the most widely used first-line treatment for advanced NSCLC, particularly for the squamous histotype. Necitumumab is nowadays the first targeted agent providing an (statistically significant) additional survival gain to squamous NSCLC patients when combined with first-line chemotherapy at the cost of an increased (although manageable) toxicity, as shown in the SQUIRE trial. Hopefully, improvement in patients’ selection by identifying reliable predictive markers and the combination with new agents may help to maximize the benefit of this targeted treatment, which is currently limited by a not optimal cost–benefit ratio.

KEYWORDS:

• Necitumumab
• EGFR
• monoclonal antibody
• squamous
• NSCLC

Article Highlights

• Despite remarkable advances in the treatment of metastatic NSCLC, squamous histotype still represents a relatively unmet medical need, considering the limited amount of therapeutical options available.

• In the SQUIRE trial, the addition of necitumumab to cisplatin–gemcitabine significantly improved OS, PFS, and DCR in previously untreated squamous NSCLC patients.

• The most common adverse events, including skin toxicity and hypomagnesemia, were manageable and shared with other anti-EGFR agents; while hypersensitivity infusion-related reactions were very rare due to the full human origin of necitumumab.

• In patients treated with necitumumab combined with cisplatin–gemcitabine, EGFR expression and copy number gain were correlated with better outcome, although the predictive value of these factors has to be confirmed in further prospective trials.

• The combination of necitumumab with other agents or immune checkpoint inhibitors might be a promising strategy to improve outcome of NSCLC patients.

• This box summarizes key points contained in the article.

Box 1. Drug summary box.

Declaration of Interest

G Tortora and E Bria are supported by Associazione Italiana Ricerca Cancro (AIRC grant nos. IG 20583 to E Bria; 5 × 1000 12182 to G Tortora); S Pilotto, G Tortora, and E Bria are supported by Fondazione Cariverona (2015.0872); S Pilotto and E Bria were supported by the International Association for the Study of Lung Cancer (IASLC). The funding agencies had no role in the interpretation of data and in the writing of the manuscript. The authors 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 was not funded.