Clinical potential of necitumumab in non-small cell lung carcinoma

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.

Challenges and future of biomarker tests in the era of precision oncology: Can we rely on immunohistochemistry (IHC) or fluorescencein situhybridization (FISH) to select the optimal patients for matched therapy?

“…On the basis of the observations made in the SQUIRE trial, the US FDA approved necitumumab plus gemcitabine-cisplatin combination for use as a first-line therapy option in metastatic squamous cell NSCLC [ 135 ]. Additionally, necitumumab has also been authorized for use by the European Commission (the Committee for Medicinal Products for Human Use; CHMP) for advanced squamous NSCLC in combination with gemcitabine plus cisplatin [ 136 ]. Of note, in contrast to the US FDA approval, European Commission limited the approved indication to advanced squamous NSCLC with EGFR expression although they did not specify the methods for testing the expression of EGFR [ 136 ].…”

“…Additionally, necitumumab has also been authorized for use by the European Commission (the Committee for Medicinal Products for Human Use; CHMP) for advanced squamous NSCLC in combination with gemcitabine plus cisplatin [ 136 ]. Of note, in contrast to the US FDA approval, European Commission limited the approved indication to advanced squamous NSCLC with EGFR expression although they did not specify the methods for testing the expression of EGFR [ 136 ]. This is a good example where a clinically meaningful biomarker based subgroup analysis influenced actual approved indication of the treatment regimen.…”

Preparation of a phosphotyrosine-protein standard for use in semiquantitative western blotting with enhanced chemiluminescence

“…Patients whose tumor showed a strong pTyr-RTK signal, pTyr-EGFR for example, would likely respond to the corresponding inhibitor, e.g. Necitumumab, a WT EGFR inhibitor [5]. This approach might be directly useful for precision medicine testing, or more likely indirectly useful for finding RNA-seq fingerprints for a predictive genomic assay.…”

EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma

“… 3 – 5 Tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment option for advanced adenocarcinoma patients, and have significantly improved the treatment outcomes for patients. 6 EGFR–TKIs combined with chemotherapy were approved as a second-line treatment option in USA and Europe for advanced squamous carcinoma patients. 6 Currently, SCC patients still have limited treatment options in addition to chemotherapy, 7 thus resulting in a poorer treatment outcome as compared to adenocarcinoma patients.…”

“… 6 EGFR–TKIs combined with chemotherapy were approved as a second-line treatment option in USA and Europe for advanced squamous carcinoma patients. 6 Currently, SCC patients still have limited treatment options in addition to chemotherapy, 7 thus resulting in a poorer treatment outcome as compared to adenocarcinoma patients. 7 , 8 …”