Erlotinib and Chemotherapy for Patients With Stage IB-IIIA NSCLC With EGFR Mutations (ECON)

Chemotherapy and surgery in combination represents the standard of care for patients with resectable stage IB-IIIA NSCLC. However, the 5-year survival continues to be disappointing despite this standard of care. This study incorporates targeted therapy with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) as part of a multimodality strategy for stage IB-IIIA resectable NSCLC tumors with a known EGFR activating mutation. The rationale for including only patients with EGFR mutations is based on recent data that reported that patients with advanced NSCLC whose tumor harbor EGFR activating mutations had an objective response rate of 71% with gefitinib compared with a 1% objective response rate in patients with EGFR wild-type tumors.

Inclusion criteria

• Pathologic confirmation of NSCLC
• Patients must have previously untreated stage IB-IIIA NSCLC (T1-3N0-2M0)
• Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q)
• Patients must be candidates for resection with curative intent
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded on CT)
• Age greater or equal to 18 years
• Karnofsky performance status greater or equal to 70%
• Normal marrow function: leukocytes greater than or equal to 3,000/μl, absolute neutrophil count greater than or equal to 1,500/μl, platelets greater than or equal to 100,000/μl, hemoglobin greater than or equal to 9 gm/dl
• Adequate renal function, with creatinine less than or equal to 1.3 mg/dl or calculated creatinine clearance greater to or equal to 60ml/min by Cockroft and Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl)
• Adequate hepatic function: Total bilirubin within normal limits, AST < 1.5 X UNL, alkaline phosphatase < 1.5 X UNL
• Women of childbearing age must have a negative urine or blood pregnancy test
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Patients must have ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Prior chemotherapy or radiation therapy, with the exception of chemotherapy for nononcologic conditions (ie, methotrexate for the treatment of rheumatoid arthritis)
• Prior treatment with gefitinib, erlotinib, or other drugs that target EGFR
• Patients must not be receiving any other investigational agents
• Any evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
• Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (CTCAE grade 2 or higher)
• Peripheral neuropathy > grade 1
• Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs.
• Other serious illness or medical condition including unstable cardiac disease requiring treatment, history of significant neurologic or psychiatric disorders (including psychotic disorders, dementia, or seizures), or active uncontrolled infection
• Women who are pregnant or breast-feeding
• Psychiatric illness or social situation that would limit compliance with study requirements