The aim of this study is to assess the superiority of docetaxel in comparison to erlotinib in second line in wild-type EGFR tumour patients.

Erlotinib is registered in all patients affected with NSCLC in second and subsequent lines with a small benefit on Overall Survival. Recent evidence suggest that patients with EGFR mutations have a clear benefit when they are treated with EGFR tyrosine kinase inhibitors, while the role of these drugs in wild-type EGFR patients, that are representing the large majority (about 85-90%), is still unclear and no properly planned trials assessed before this issue. Recently, indirect evidence on subgroup analyses on randomized trial suggest that chemotherapy might be superior to erlotinib in wild-type EGFR patients.

Moreover, several authors do not recommend the use of EGFR determined with immunohistochemistry (IHC) or FISH because they do not reproducibly predict outcome.

For these reasons the protocol was amended in May 2011 in a superiority trial of docetaxel versus erlotinib, while the first version was aimed to assess the interaction with biomarkers.

Inclusion Criteria:

• Age 18 years or older
• Histological or cytological confirmation of NSCLC (may be from initial diagnosis of NSCLC or subsequent biopsy). Only patients with available tissue samples may be included in the study
• Absence of EGFR mutations of exons 19 or 21 (randomization)
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
• One prior platinum-based at adequate doses and taxane free regimen
• Measurable (uni-dimensional) disease by RECIST in a lesion not previously irradiated or non-measurable disease
• ECOG-PS 0-2
• ANC greater than 1.5 x 109/L and platelets greater than 100 x 109/L
• Bilirubin level either normal or <1.5xULN
• AST (SGOT) and ALT (SGPT) <2.5xULN (≤5 x ULN if liver metastases are present)
• Serum creatinine <1.5xULN
• Effective contraception for both, male and female pts, if the risk of conception exists
• Recovery from all acute toxicities of prior therapies
• Provision of written informed consent to the analysis of biological markers (registration)
• Provision of written informed consent to enter the randomized part of the study (randomization)

Exclusion Criteria:

• Prior therapy with an experimental agent whose primary mechanism of action is inhibition of EGFR or its associated tyrosine kinase
• Prior chemotherapy with taxanes
• Newly diagnosed CNS metastases that have not yet been treated with surgery and/or radiation. Pts with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they have evidence of clinically SD (no steroid therapy or steroid dose being tapered) for at least 28 daysLess than 14 days since completion of prior radiotherapy or persistence of any radiotherapy related toxicity
• Any unresolved chronic toxicity from previous anticancer therapy that, in the opinion of the investigator, makes it inappropriate for the patient to be enrolled in the study Known severe hypersensitivity to erlotinib or any of the excipients of this product
• Known hypersensitivity to docetaxel, polysorbate 80 or other drugs formulated with polysorbate 80, or any of the excipients of docetaxel
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Unable to swallow tablets
• Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic or patients with uncomplicated progressive lymphangitic carcinomatosis need not be excluded)
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
• As judged by the investigator, any inflammatory changes of the surface of the eye
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study