‘Osimertinib – as the Front Line Therapy for Treatment of Lung Cancer (NSCLC)’

Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Patients with NSCLC require a complete staging workup to evaluate the extent of disease, because stage plays a major role in determining the choice of treatment. Approximately one-half of patients with epidermal growth factor receptor (EGFR) mutation-(NSCLC) develop resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) due to a secondary T790M mutation. 71% are likely to benefit from osimertinib. There have been several reports about the secondary resistance to osimertinib treatment in T790M positive patients. Case presentation : A 62-year-old male never smoker who presented with stage IV EGFR L858R-positive adenocarcinoma developed EGFR T790M mutation after 14 months of treatment with erlotinib combined with thoracic radiotherapy as first-line therapy. The patient was initiated on osimertinib treatment with T790M mutation detected (14.4%), and the disease progression ceased for 2 months later. This prospective observational study enrolled patients with EGFR mutation-positive advanced/metastatic NSCLC who reported disease progression during treatment with first- or second-generation EGFR TKIs. Data regarding sampling methods for T790M mutation testing (plasma sample, cytology or tissue biopsy) and the treatment strategies after disease progression were recorded prospectively. Osimertinib, the third-generation EGFR inhibitor, has favorable pharmacological properties for both efficacy and toxicity. It has a strong affinity for sensitizing and resistance (T790M) mutations, thereby achieving efficacy as both an initial therapy and after EGFR TKI failure. Additionally, it has a minimal inhibition of wild-type EGFR, resulting in lower rates and severity of dermatological and GI toxicities as per case report. This so far have been ultimately providing the greatest duration of disease control, the longest overall survival of 23 months, than those of other targeted therapies for lung cancer. In the light of osimertinib’ s impressive activity subsequent studies evaluated its efficacy as an effective agent in first-line therapy.