Case Report
Interstitial Lung Disease Arising From Erlotinib Treatment in a Caucasian Patient

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Introduction

Our knowledge of lung cancer has changed with the discovery of oncogenic driver alterations in a subset of non–small-cell lung cancer (NSCLC) patients. EGFR mutations were the first drivers to enter into the lung cancer scenario. It is present in 10% to 30% of NSCLC patients, depending on the population studied. EGFR mutations are more frequent in women, nonsmokers, disease of adenocarcinoma histology, and subjects of Asian ethnicity.1, 2, 3

EGFR is a tyrosine kinase protein receptor located on the tumor cell membrane. By binding to its ligand (EGF, TGF-α), a cascade of cellular proliferation is activated by electrical signals, producing tumor reproduction, forming new blood vessels (angiogenesis), and resulting in tumor cell survival.1, 2, 3 Approximately 90% of these mutations are located in exons 19 and 21. In cases in which the mutation is present, patients treated with EGFR tyrosine kinase inhibitors (TKI) have a better response rate, progression-free survival (PFS), and quality of life compared to those who received chemotherapy.1, 2, 3, 4, 5, 6, 7, 8, 9, 10

EGFR mutations can result in increased sensitivity to treatment directed against these specific alterations. However, a subset of EGFR mutations is associated with resistance to these treatments. There are 2 types of anti-EGFR drugs in cancer treatment: monoclonal antibodies and TKI. TKI are the only treatments that have demonstrated a benefit in NSCLC patients. TKI interact with the intracellular domain of EGFR, inhibiting ligand-induced phosphorylation. These molecules compete with the ATP (adenosine 5′-triphosphate) binding site on the intracellular domain of the tyrosine kinase. Three drugs (erlotinib, gefitinib, and afatinib) are currently approved for the treatment of EGFR-mutant NSCLC patients.

Despite good initial and prolonged response, all patients experience relapse. Different molecular alterations, such as the presence of a secondary mutation in exon 20 of the EGFR gene, which is the replacement of a methionine residue by one of threonine at position 790 of the kinase domain (T790M), has been described as mechanisms of acquired resistance to these treatments. This mutation is present in approximately 50% of tumors with acquired resistance to TKI.11 Additional mechanisms of acquired resistance to TKI, such as bypass activation of HER3, MET, or EGFR amplification, have been described.12, 13, 14, 15

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Case Presentation

The patient, a 63-year-old nonsmoking man, complained of cough in February 2008. Thoracic radiography in April 2008 revealed parahilar infiltration. Computed tomography (CT) revealed supraclavicular, anterior mediastinal adenopathy (13.3 mm), right parahilar tumor (45 mm), and multiple lung and liver metastases; brain metastases were revealed by brain scan. Bronchoscopy biopsy was negative. Liver biopsy confirmed adenocarcinoma that was CK7 positive and TTF1 positive. The patient was diagnosed

Discussion

NSCLC patients with EGFR mutations in exons 19 and 21 have a better response rate and PFS when treated with an EGFR TKI than with chemotherapy. In the first-line setting, several phase 3 trials have demonstrated the superiority of TKI over chemotherapy, indicating that this is the best choice for patients, including the patient reported here.4, 5, 6, 7, 8, 9, 10 However, EGFR TKI are not free of toxicity. The most common adverse events are rash and diarrhea,4, 5, 6, 7, 8, 9, 10 usually of low

Conclusion

Some reports have shown that retreatment with EGFR TKI after ILD may be possible. EGFR TKI is the best treatment choice in patients with EGFR-mutated NSCLC and should therefore be considered after ILD in these patients.

The underlying mechanism of ILD remains unclear. More investigation is needed to better identify and prevent the underlying ILD risk factors associated with TKI.

Disclosure

The authors have stated that they have no conflicts of interest.

References (29)

  • J.L. Dallas et al.

    Successful erlotinib rechallenge after erlotinib-induced interstitial lung disease

    J Thorac Oncol

    (2011)
  • K.F. Wang et al.

    Both gefitinib and erlotinib induced drug-related interstitial lung disease in a patient with pulmonary adenocarcinoma

    J Chin Med Assoc

    (2013)
  • T.J. Lynch et al.

    Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib

    N Engl J Med

    (2004)
  • W. Pao et al.

    EGF receptor mutations are common in lung cancer from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib

    Proc Natl Acad Sci U S A

    (2004)
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