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Título
Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer
Autor(es)
Bonomi, P D | Gandara, D | Hirsch, F R | Kerr, K M | Obasaju, C | Paz Ares, Luis Gonzaga CNIO | Bellomo, C | Bradley, J D | Bunn, P A | Culligan, M | Jett, J R | Kim, E S | Langer, C J | Natale, R B | Novello, S | Pérol, M | Ramalingam, S S | Reck, M | Reynolds, C H | Smit, E F | Socinski, M A | Spigel, D R | Vansteenkiste, J F | Wakelee, H | Thatcher, N
Fecha de publicación
2018-08-01
Cita
Ann Oncol. 2018; 29(8):1701-1709.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Design: Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results: Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents. Conclusions: Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.
Palabras clave
GROWTH-FACTOR RECEPTOR | PHASE-III TRIAL | CLINICAL-PRACTICE GUIDELINES | CISPLATIN PLUS GEMCITABINE | OPEN-LABEL | STAGE IV | 1ST-LINE THERAPY | FOLLOW-UP | CETUXIMAB | CHEMOTHERAPY
Descripción
The concept of predictive biomarkers for EGFR-directed mAbs
addressed in this article were originally discussed at a meeting
convened by Eli Lilly and Company that covered topics for
physician education on SqCLC, for which participants, includ-
ing some of the authors on this publication, received an honor-
arium. This publication was developed separately from the
meeting, and the authors received no payment in relation to the
development of this publication. The authors would like to
thank Charlene Rivera, PhD and Rob Kite, BSc (Hons), at
Complete HealthVizion for assistance with writing and revising
the draft manuscript on the basis of detailed feedback from all
authors. Primary responsibility for the opinions, conclusions,
and interpretation of data lay with the authors, and all authors
approved the final version of the manuscript.
Versión en línea
DOI
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