Current knowledge of Ipilimumab and its use in treating non-small cell lung cancer

ABSTRACT

Introduction: The systemic treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the identification of actionable mutations and the use of targeted agents. Unfortunately, many tumors will acquire resistance and >75% of NSCLC cases lack for an actionable gene aberration. In this setting, immunotherapy rises as effective therapeutic where immune checkpoint inhibitors have entered or are entering the market in many neoplasms, including NSCLC. Ipilimumab is a monoclonal antibody targeting CTLA-4, promoting T-cell activation and its subsequent anti-tumoral immune effect. Ipilimumab might have a very important role in NSCLC as it does in melanoma because of its synergistic effect with PD-1/PDL-1 inhibitors.

Areas covered: We summarize current results of clinical studies of ipilimumab for efficacy and safety in NSCLC and also the current knowledge about potential biomarkers for its efficacy.

Expert Opinion: Combined use of PD-1/PDL-1 and anti-CTL4 inhibitors increases the efficacy against NSCLC and it is a very promising approach not only in NSCLC but also in small cell lung cancer (SCLC) for first or second-line therapy. It’s very important to identify biomarkers that can better select the population of patients that benefit the most with these checkpoint inhibitors.

KEYWORDS:

• Non-small cell lung cancer
• CTLA-4
• immunotherapy
• biomarkers

Box 1. Drug summary box

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Article highlights

• Ipilimumab as single agent have limited efficacy in NSCLC however, combination with PD-1 inhibitors have promising results.

• Offering radiotherapy before ipilimumab administration offers new therapeutic opportunities for this drug.

• Ipilimumab have a manageable safety profile while the combination with anti PD-1 inhibitors increase the frequency of grade 3/4 treatment-related adverse events.

• New predictive biomarkers should improve the selection of patients who will benefit from the combination of ipilimumab plus PD-1 inhibitors.

Declaration of interest

LE Raez receives research support from BMS, Merck and Roche/Genentech. 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

One of the reviewers on this paper has received honoraria from Astra Zeneca, Boehringer Ingelheim, BMS, MSD and Roche. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.