Osimertinib (AZD9291) in First-line Locally Advanced or Metastatic NSCLC Patients With EGFR and EGFR T790M

Inclusion Criteria

• Patient aged 18 years or older
• Patients with histological confirmation of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with an activating EGFR mutation and concomitant T790M mutation who are not candidates for local curative treatment.
• Patients with a M1a stage according to the TNM version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease that is not a candidate for curative treatment (including patients who progress after chemoradiotherapy in stage III disease).
• Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally.
• ECOG (Eastern Cooperative Oncology Group) performance status less than or equal to 2.
• Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable brain metastases are eligible for the study.
• Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumor or metastatic tumor tissue, within the 60 days prior to study entry.
• Life expectancy ≥12 weeks.
• Adequate hematologic function:
• Absolute neutrophil count (ANC) > 1.5 x 109/L
• platelet count > 100.0 x109/L
• hemoglobin > 9.0 g/dL (> 6.2 mmol/L).
• Adequate coagulation: INR ≤ 1.5.
• Adequate liver function
• Adequate renal function.
• Capacity to swallow, patient capable of completing treatment and accessible, ensuring proper follow-up.
• Patients able to complete study and within geographical proximity allowing for adequate follow-up.
• Resolution of all acute toxic effects of previous anti-cancer therapy (which can only be adjuvant or neoadjuvant) or surgical interventions not exceeding grade ≤ 1 according to the NCI CTCAE version 4.0 (except for alopecia or other side effects that the investigator does not consider to be a risk to patient safety).
• All men or women of childbearing potential must use a contraception method during the study treatment and for at least 12 months after the last dose of the study drug.
• Signed and dated informed consent form

Exclusion Criteria

• Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy.
• Patients diagnosed with another lung cancer subtype, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small-cell lung cancer component.
• Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally.
• Patients who have received prior antineoplastic treatment for advanced disease.
• Second active neoplasia
• Patients with just one measurable or evaluable tumor lesion that has been resected or irradiated prior to their enrollment in the study.
• Medical history of Interstitial Lung Disease (ILD) induced by drugs, radiation pneumonitis requiring steroid treatment or any evidence of clinically active ILD.
• Corrected QT Interval (QTc) >470 msec, obtained from 3 ECGs at rest, using the QTc value determined according to the clinical screening ECG machine.
• Any clinically significant abnormality in ECG rhythm, conduction or morphology at rest.
• Any factor that increases the risk of QTc prolongation or risk of irregular heartbeat or sudden inexplicable death under the age of 40 in first-degree relatives or any concomitant medications that prolong the QT interval.
• Uncontrolled, active or symptomatic metastases of CNS, carcinomatous meningitis or leptomeningeal disease indicated by known clinical symptoms, cerebral edema and/or progressive neoplasia. Patients with history of CNS metastasis or compression of the spinal cord are eligible if they have received local final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained clinically stable without using anticonvulsants and corticosteroi