Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

P. D. Bonomi* (Corresponding Author), D. Gandara, F. R. Hirsch, K. M. Kerr, C. Obasaju, L. Paz-Ares, C. Bellomo, J. D. Bradley, P. A. Bunn, M. Culligan, J. R. Jett, E. S. Kim, C. J. Langer, R. B. Natale, S. Novello, M. Pérol, S. S. Ramalingam, M. Reck, C. H. Reynolds, E. F. SmitM. A. Socinski, D. R. Spigel, J. F. Vansteenkiste, H. Wakelee, N. Thatcher

*Corresponding author for this work

Research output: Contribution to journalReview article

4 Citations (Scopus)
4 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)1701-1709
Number of pages9
JournalAnnals of Oncology
Volume29
Issue number8
Early online date14 Jun 2018
DOIs
Publication statusPublished - 1 Aug 2018

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Squamous Cell Neoplasms
Epidermal Growth Factor Receptor
Lung Neoplasms
Biomarkers
Monoclonal Antibodies
Non-Small Cell Lung Carcinoma
Gene Dosage
Immunotherapy
erbB-1 Genes
Angiogenesis Inhibitors
Therapeutics
Combination Drug Therapy
Phase III Clinical Trials
Proteins
Gene Amplification

Keywords

  • EGFR-directed monoclonal antibodies
  • Non-small-cell lung cancer
  • Squamous cell lung cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer. / Bonomi, P. D. (Corresponding Author); Gandara, D.; Hirsch, F. R.; Kerr, K. M.; Obasaju, C.; Paz-Ares, L.; 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.

In: Annals of Oncology, Vol. 29, No. 8, 01.08.2018, p. 1701-1709.

Research output: Contribution to journalReview article

Bonomi, PD, Gandara, D, Hirsch, FR, Kerr, KM, Obasaju, C, Paz-Ares, L, Bellomo, C, Bradley, JD, Bunn, PA, Culligan, M, Jett, JR, Kim, ES, Langer, CJ, Natale, RB, Novello, S, Pérol, M, Ramalingam, SS, Reck, M, Reynolds, CH, Smit, EF, Socinski, MA, Spigel, DR, Vansteenkiste, JF, Wakelee, H & Thatcher, N 2018, 'Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer', Annals of Oncology, vol. 29, no. 8, pp. 1701-1709. https://doi.org/10.1093/annonc/mdy196
Bonomi, P. D. ; Gandara, D. ; Hirsch, F. R. ; Kerr, K. M. ; Obasaju, C. ; Paz-Ares, L. ; 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. / Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer. In: Annals of Oncology. 2018 ; Vol. 29, No. 8. pp. 1701-1709.
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title = "Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer",
abstract = "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.",
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author = "Bonomi, {P. D.} and D. Gandara and Hirsch, {F. R.} and Kerr, {K. M.} and C. Obasaju and L. Paz-Ares and C. Bellomo and Bradley, {J. D.} and Bunn, {P. A.} and M. Culligan and Jett, {J. R.} and Kim, {E. S.} and Langer, {C. J.} and Natale, {R. B.} and S. Novello and M. P{\'e}rol and Ramalingam, {S. S.} and M. Reck and Reynolds, {C. H.} and Smit, {E. F.} and Socinski, {M. A.} and Spigel, {D. R.} and Vansteenkiste, {J. F.} and H. Wakelee and N. Thatcher",
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T1 - Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

AU - Bonomi, P. D.

AU - Gandara, D.

AU - Hirsch, F. R.

AU - Kerr, K. M.

AU - Obasaju, C.

AU - Paz-Ares, L.

AU - Bellomo, C.

AU - Bradley, J. D.

AU - Bunn, P. A.

AU - Culligan, M.

AU - Jett, J. R.

AU - Kim, E. S.

AU - Langer, C. J.

AU - Natale, R. B.

AU - Novello, S.

AU - Pérol, M.

AU - Ramalingam, S. S.

AU - Reck, M.

AU - Reynolds, C. H.

AU - Smit, E. F.

AU - Socinski, M. A.

AU - Spigel, D. R.

AU - Vansteenkiste, J. F.

AU - Wakelee, H.

AU - Thatcher, N.

N1 - Writing assistance was funded by Eli Lilly and Company (no grant numbers apply).

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - EGFR-directed monoclonal antibodies

KW - Non-small-cell lung cancer

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