With regard to the last point, prospectively specified analysis plans for randomized phase III studies are

fundamental to achieve reliable results. Paradoxically, many of the currently ongoing trials for adjuvant treatment of resected NSCLC are designed in order to select patients on the basis of genetic features when ‘old-fashioned’ chemotherapeutics are experimented (i.e. the Spanish Customized Adjuvant Treatment, SCAT, randomizing patients on the basis of BRCA overexpression, the and the International TAilored Chemotherapy Adjuvant trial, ITACA, with a two-step randomization taking into account both levels of ERCC1 and TS tissue expression), and with a non-selection strategy, when adopting ‘new and targeted’ agents (i.e. erlotinib and bevacizumab in the RADIANT, 10058-F4 nmr and in the ECOG E1505 trial, respectively). In an ideal scenario, when complete information on predictive factors and proper selection of patients can be definitely obtained in the early phases of drug development, the conduction of subsequent phase III study could be optimized. Unfortunately, this ideal scenario occurs rarely, also with molecularly targeted agents. selleck compound When planning a phase III trial comparing an experimental treatment with the standard, we

often have evidence supporting a predictive role of a check details marker (M) about the efficacy of the experimental treatment: according to that evidence, patients with expression of the marker (M+)

are expected to potentially benefit of the experimental treatment, and patients with absence of expression of the marker (M-) are not [32]. In such a scenario, different strategies based on prospective determination of marker status are theoretically possible: (a) “” randomize-all “” strategy, randomization between standard and experimental treatment without selection, bu with stratification based on the status of the marker; (b) “” targeted “” design, randomization between standard and experimental treatment only in patients selected according to the status of the marker; (c) “” customized “” strategy (also called “” marker-based strategy “”), randomization between standard arm, in which the treatment is the same for all patients, and a personalized arm, in which treatment is chosen based on the marker www.selleck.co.jp/products/pci-32765.html status of each patient. The “” randomize-all “” strategy is useful if investigators are not sure of the complete lack of efficacy of experimental treatment in M- patients. Marker is prospectively assessed in all patients, allowing stratification, but all patients are randomized, regardless of the marker status. Interaction between marker status and treatment effect can be formally tested by an interaction test. On the contrary, predictive role of the marker should not be addressed with separate comparison in M+ and M- patients, because this approach, as stated before, would be associated with a high risk of false results [29].