Clinical potential of necitumumab in non-small cell lung carcinoma
1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; Lung Cancer Unit, IRCCS AOU San Martino IST; Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy.
Abstract:
Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC) are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR) is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial); by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial). On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment.
Insights
Necitumumab offers a survival benefit for advanced squamous non-small cell lung cancer (NSCLC) when combined with chemotherapy. This EGFR inhibitor is approved for patients with EGFR-expressing tumors, improving treatment options.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Advanced non-small cell lung cancer (NSCLC), particularly squamous cell carcinoma, requires novel therapeutic strategies.
- Epidermal growth factor receptor (EGFR) is a key target, frequently overexpressed in squamous NSCLC.
- Necitumumab, a monoclonal antibody, inhibits EGFR signaling and mediates antibody-dependent cell cytotoxicity.
Purpose of the Study:
- To review the efficacy and tolerability of necitumumab in advanced NSCLC.
- To define the role of necitumumab within the current NSCLC treatment landscape.
Main Methods:
- Systematic review of published data on necitumumab in advanced NSCLC.
- Analysis of Phase III trials (SQUIRE and INSPIRE) evaluating necitumumab in combination with chemotherapy.
Main Results:
- Necitumumab demonstrated a significant survival benefit in squamous NSCLC when combined with cisplatin and gemcitabine (SQUIRE trial).
- No survival benefit was observed in non-squamous NSCLC (INSPIRE trial).
- Necitumumab is approved for first-line treatment of advanced squamous NSCLC in EGFR-expressing patients.
Conclusions:
- Necitumumab is an effective first-line treatment option for advanced squamous NSCLC with EGFR expression.
- The drug's efficacy is histology-dependent, showing benefit only in squamous NSCLC.
- Further evaluation of necitumumab's tolerability and role in clinical practice is warranted.
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