title: Rationale for treatment and study design of tailor: a randomized phase III trial of second-line erlotinib versus docetaxel in the treatment of patients affected by advanced non-small-cell lung cancer with the absence of epidermal growth factor receptor mutations.
abstract: We present the rationale and study design of the Tarceva Italian Lung Optimization trial phase III, multicenter, open-label, randomized trial on efficacy of second-line therapies in different subgroups of non-small-cell lung cancer (NSCLC) patients identified using molecular and clinical evaluations. To date, we can assume that advanced NSCLC epidermal growth factor receptor (EGFR)-mutated patients benefit from EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, whereas their role in the treatment of patients who do not have EGFR mutations is controversial. The aim of this study is to assess whether it is possible to optimize second-line treatment in NSCLC patients with absence of EGFR mutations. Moreover, the predictive value of the K-ras mutation, EGFR protein expression, and EGFR gene copy number, as well as a smoking habit and histotype for determining a different effect of erlotinib compared with chemotherapy will be assessed in patients who do not have EGFR mutations. The primary endpoint is overall survival; the secondary endpoints are progression-free survival, response rate, quality of life, and toxicity. We have planned to collect blood samples to identify different prognosis-related polymorphisms and to assess their sensitivity and specificity in the detection of EGFR and K-ras mutations with respect to histologic samples.
authors.affiliation: Dipartimento di Oncologia Ospedale Fatebenefratelli e Oftalmico, Milan.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Farina
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.forename: Olga
authors.initials: O
authors.lastname: Martelli
authors.forename: Ida
authors.initials: I
authors.lastname: Pavese
authors.forename: Andrea
authors.initials: A
authors.lastname: Mancuso
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolini
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Daniele
authors.initials: D
authors.lastname: Fagnani
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valmadre
authors.forename: Antonio
authors.initials: A
authors.lastname: Ardizzoia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tomirotti
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.forename: Marina Chiara
authors.initials: MC
authors.lastname: Garassino
authors.forename: Alberto
authors.initials: A
authors.lastname: Scanni
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors