Treatment with Osimertinib in Patients with NSCLC After Disease Progression on Previous Therapy – Case Study
We present a case study of a patient with non-small cell lung cancer (NSCLC) with a proven activating mutation of the epidermal growth factor receptor (EGFR) gene, who developed resistance to the first-generation EGFR tyrosine kinase inhibitor (TKI) gefitinib during treatment. After the secondary mutation EGFR T790M was confirmed, osimertinib, a third-generation EGFR TKI, was introduced, resulting in disease regression, which is ongoing. This case study illustrates the significance of the role of osimertinib in the treatment of patients with NSCLC with an activating EGFR mutation, whose disease progresses during treatment with first and second-generation EGFR TKIs due to the emergence of the secondary EGFR T790M mutation.
EGFR Tyrosine Kinase Inhibitors in NSCLC Treatment – the Position of Osimertinib
NSCLC accounts for approximately two-thirds of all lung tumors. Traditionally, they have been considered less sensitive to chemotherapy and radiotherapy. Molecular genetic methods have revealed the genetic heterogeneity of these tumors, allowing treatment to be individualized according to the specific detected genetic mutation. In the Czech Republic, NSCLC with adenocarcinoma histology, nonspecified histology, and at the request of a clinical physician, NSCLC with squamous cell histology, among others, is reflexly tested for the presence of an activating EGFR mutation. If this mutation is confirmed and other conditions are met, the patient can initiate treatment with an EGFR tyrosine kinase inhibitor (TKI).
During treatment with first and second-generation EGFR TKIs (gefitinib, erlotinib, afatinib), resistance to this treatment can be expected over time. In 60% of cases, this resistance is due to the EGFR T790M mutation. Osimertinib, a third-generation EGFR TKI, has been approved in the Czech Republic since 2016 for the treatment of patients with locally advanced or metastatic NSCLC with a proven T790M mutation in the EGFR gene due to resistance to other EGFR TKIs, and since 2018 as a first-line treatment for patients with NSCLC with a confirmed activating EGFR gene mutation.
Case Description
In April 2015, a 59-year-old non-smoking woman was diagnosed with bronchogenic carcinoma of the right upper lung lobe at stage T4N2M1b (metastases to the skull bones). Histological examination of the tissue obtained by bronchial excision revealed adenocarcinoma, and molecular genetic testing confirmed the presence of an activating mutation in exon 19 of the EGFR gene. The patient met the criteria for treatment with EGFR tyrosine kinase inhibitors, and treatment with gefitinib was initiated.
This therapy resulted in a partial response and an improvement in the patient's clinical condition, with the therapeutic response lasting for 21 months. In February 2017, however, her clinical condition deteriorated, and a control chest CT scan showed disease progression. Gefitinib treatment was therefore discontinued, and chemotherapy with a combination of carboplatin and pemetrexed was initiated. However, in the following month, there was a significant deterioration in the patient's clinical condition, and imaging studies showed massive progression of lung involvement. Molecular genetic analysis of tumor cells obtained from the pleural effusion puncture confirmed the original activating mutation and the EGFR T790M mutation, which causes resistance to gefitinib.
In April 2017, treatment with osimertinib was initiated in the third treatment line. The condition rapidly improved, and after just one month of osimertinib therapy, lung x-rays showed disease regression. The patient tolerated the new treatment very well, with only a mild papular rash on the forearm and paronychia on two fingers of the left hand appearing in January 2018. These skin issues were manageable with local therapy and resolved within two months without the need to modify the osimertinib dosage. Osimertinib treatment again resulted in a partial response, confirmed by the most recent CT scan in December 2018. According to an examination in February 2019, the patient showed no clinical signs of disease progression and continued therapy with osimertinib.
Conclusion
This case study illustrates the rapid onset and long-term duration of the effect of osimertinib treatment and its significance in the therapy of patients with disease progression due to acquired EGFR T790M mutation. The treatment is generally well-tolerated by patients.
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Source: Čoupková H., Bílek O., Mužík J., et al. Osimertinib in the Treatment of Non-Small Cell Lung Carcinoma with Proven T790M Mutation. Acta Medicinae 2019; 8 (4): 22–24.
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