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EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP)

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Abstract

Background

Non-small cell lung cancer (NSCLC) has a 5-year survival of 5–16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role.

Objective

Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp.

Patients and Methods

Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status.

Results

30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3–34.6) vs. (11.0, 95% CI 8.2–16.7); p = 0.002] and OS [(37.8, 95% CI 30.9–44.7) vs. (27.1, 95% CI 12.8–41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0–44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4–42.5) (p < 0.001) and longer PFS (p = 0.043).

Conclusion

Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.

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Acknowledgements

We are grateful for the generous contribution from the Silberman and Buendía families for altruistically promoting the development of cancer research in Colombia.

Author information

Author notes

  1. Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Andrés F. Cardona, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Beatriz Wills, and Oscar Arrieta contributed equally to this work.

Authors and Affiliations

  1. Foundation for Clinical and Applied Cancer Research (FICMAC), Calle 116 No. 9–72, c. 318, Bogotá, Colombia

    Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Andrés F. Cardona, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, July Rodriguez, Jenny Avila & Melissa Bravo

  2. Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia

    Andrés F. Cardona, Leonardo Rojas, Hernán Carranza, Carlos Vargas & Jorge Otero

  3. Molecular Oncology and Biology Systems Research Group (FOX-G), Universidad El Bosque, Bogotá, Colombia

    Andrés F. Cardona

  4. Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia

    Leonardo Rojas

  5. Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico

    Zyanya Lucia Zatarain-Barrón & Oscar Arrieta

  6. Internal Medicine Department, Johns Hopkins University, Baltimore, MD, USA

    Beatriz Wills

  7. Medical Oncology Department, Hospital Clinic, Barcelona, Spain

    Noemí Reguart

  8. Clinical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica

    Luis Corrales

  9. Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina

    Claudio Martín

  10. Medical Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Luis Eduardo Pino

  11. Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Rafael Rosell

Authors
  1. Alejandro Ruiz-Patiño
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  2. Christian David Castro
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  13. Claudio Martín
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  14. Pilar Archila
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  15. July Rodriguez
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  16. Jenny Avila
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  17. Melissa Bravo
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  18. Luis Eduardo Pino
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  19. Rafael Rosell
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  20. Oscar Arrieta
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Consortia

On behalf of the Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)

Corresponding author

Correspondence to Andrés F. Cardona.

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Funding

Supported by the Foundation for Clinical and Applied Cancer Research (FICMAC, Bogotá, Colombia) research grant 017-2015.

Conflict of Interest

Andrés F. Cardona declares consulting fees or honorarium, support for travel to meetings for the study, manuscript preparation or other purposes, payment for lectures including service on speakers’ bureaus for Roche, Pfizer, Bristol-Myers Squibb, Merck, MSD, and AstraZeneca. Noemí Reguart declares advisory roles for Boehringer Ingelheim, Roche, AstraZeneca, Bristol Myers, and Pfizer, lectures and speaker bureaus for Boehringer Ingelheim, Roche, AstraZeneca, Bristol Myers, and Pfizer, and expert testimony for Boehringer Ingelheim, Roche, AstraZeneca, Bristol-Myers, and Pfizer. Luis Corrales declares that he has participated in advisory boards organized by AstraZeneca and received honoraria from AstraZeneca for lectures in scientific meetings. Oscar Arrieta declares advisory role, lectures, and speaker bureaus and expert testimony for Boehringer Ingelheim, Roche, AstraZeneca, and Lilly. Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Beatriz Wills, Hernán Carranza, Carlos Vargas, Jorge Otero, Claudio Martín, Pilar Archila, July Rodriguez, Jenny Avila, Melissa Bravo, Luis Eduardo Pino, and Rafael Rosell declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Ruiz-Patiño, A., Castro, C.D., Ricaurte, L.M. et al. EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP). Targ Oncol 13, 621–629 (2018). https://doi.org/10.1007/s11523-018-0594-x

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  • DOI: https://doi.org/10.1007/s11523-018-0594-x

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