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Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP)

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Abstract

Background

Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations.

Objective

The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression.

Patients and Methods

EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations.

Results

Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0–1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746–750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7–19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2–36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4–35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05).

Conclusions

Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.

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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. Andrés Felipe Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills contributed equally to the study.

Authors and Affiliations

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

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

  2. Foundation for Clinical and Applied Cancer Research – FICMAC, Bogotá, Colombia

    Andrés F. Cardona, Beatriz Wills, Hernán Carranza, Carlos Vargas, Jorge Otero & Pilar Archila

  3. Internal Medicine Department, Universidad El Bosque- Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Andrés F. Cardona & Martín Ignacio Zapata

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

    Oscar Arrieta & Zyanya Lucia Zatarain-Barrón

  5. Medical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia

    Leonardo Rojas

  6. Medical Oncology, Hospital Clinic, Barcelona and Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Noemí Reguart

  7. Translational Research Unit, IOR/Dexeus, University Hospital, Barcelona, Spain

    Niki Karachaliou

  8. Medical Oncology Department, Thoracic Oncology Unit, Instituto Flemin, Buenos Aires, Argentina

    Claudio Martín

  9. Medical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica

    Luis Corrales

  10. Medical Oncology Department, UdeLAR, Montevideo, Uruguay

    Mauricio Cuello

  11. Clinical Oncology Group, Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Luis E. Pino

  12. Medical Oncology Department, Catalan Institute of Oncology-ICO, Barcelona, Spain

    Rafael Rosell

Authors
  1. Andrés F. Cardona
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  2. Oscar Arrieta
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  18. Zyanya Lucia Zatarain-Barrón
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Corresponding author

Correspondence to Andrés F. Cardona.

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Funding

Funding Supported by the Foundation for Clinical and Applied Cancer Research -FICMAC (Bogotá, Colombia) research grant 018–2014.

Conflict of Interest

Andrés F. Cardona has received consulting fees or honorarium, support for travel to meetings for the study, manuscript preparation or other purposes, and payment for lectures including service on speakers bureaus from Roche, Pfizer, Bristol-Meyers Squibb, Merck, MSD, and AstraZeneca. Noemí Reguart has received consulting fees or honorarium for advisory roles, payment for lectures including service on speaker bureaus, and has given expert testimony for Boehringer Ingelheim, Roche, AstraZeneca, Bristol-Myers Squibb, and Pfizer. Luis Corrales has participated in advisory boards organized by AstraZeneca and received honoraria from AstraZeneca for lectures in scientific meetings. Carlos Ortiz has received consulting fees or honorarium for advisory boards for Pfizer, Amgen, and Roche.

All other authors declare no conflict of interest.

Disclaimer

Preliminary results from this study were previously presented during the 2015 European Cancer Congress – ESMO (25 September 2015, Vienna, Austria), during the Latin American Lung Cancer Conference - LALCA (25–27 August 2016, Panamá City, Panamá), and during the 17th World Conference on Lung Cancer – IASLC (4–7 December 2016, Vienna, Austria).

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Latin American Consortium for the Study of Lung Cancer

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Cardona, A.F., Arrieta, O., Zapata, M.I. et al. Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP). Targ Oncol 12, 513–523 (2017). https://doi.org/10.1007/s11523-017-0497-2

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