2024-03-29T12:01:08Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/68202023-10-06T09:39:01Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Bonomi, P D
author
Gandara, D
author
Hirsch, F R
author
Kerr, K M
author
Obasaju, C
author
Paz Ares, Luis Gonzaga
author
Bellomo, C
author
Bradley, J D
author
Bunn, P A
author
Culligan, M
author
Jett, J R
author
Kim, E S
author
Langer, C J
author
Natale, R B
author
Novello, S
author
Pérol, M
author
Ramalingam, S S
author
Reck, M
author
Reynolds, C H
author
Smit, E F
author
Socinski, M A
author
Spigel, D R
author
Vansteenkiste, J F
author
Wakelee, H
author
Thatcher, N
author
2018-08-01
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.
Ann Oncol. 2018; 29(8):1701-1709.
0923-7534
http://hdl.handle.net/20.500.12105/6820
29905778
10.1093/annonc/mdy196
1569-8041
Annals of oncology : official journal of the European Society for Medical Oncology
GROWTH-FACTOR RECEPTOR
PHASE-III TRIAL
CLINICAL-PRACTICE GUIDELINES
CISPLATIN PLUS GEMCITABINE
OPEN-LABEL
STAGE IV
1ST-LINE THERAPY
FOLLOW-UP
CETUXIMAB
CHEMOTHERAPY
Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer