Based on 149 of the required 514 deaths, no difference in OS could be detected [33]. ‘Tailoring’ maintenance therapy: which agent to which patient and future perspectives As highlighted in the previous paragraphs, evidence on the continued (maintenance) use of the same third-generation agent employed in the induction regimen GDC-0449 remains inconclusive with respect to gemcitabine and frankly negative in terms of cost/benefit ratio with respect to weekly paclitaxel [20–22, 34].

Nowadays, available data about pemetrexed in maintenance setting do not answer to the question see more if this approach could be useful in those patients responding to a first line with platinum compound and pemetrexed and the answer will be available soon from a randomized trial

comparing pemetrexed versus placebo in patients who do not progress following four cycles of pemetrexed plus cisplatin learn more [35]. Positive data in terms of cost-effectiveness switching to pemetrexed, which employment in non-squamous NSCLC is really cost-effective, are driven by its impact on PFS and OS [36]. This is indeed a crucial point: resources use and costs involved with this new paradigm in the clinic, would all argue for a meaningful improvement in survival as a critical necessity from a practical standpoint. As a consequence, the usefulness of maintenance therapy has to be based on a clearly defined, reproducible and measurable endpoint. Using PFS as the basis for the adoption of a new therapeutic approach, may be considered as a limitation due to the variability in the definition of progression and frequency of response assessment across studies; in this context, it seems very relevant to standardize PFS measurement in definitive phase III trials. For example, in the Fidias trial, patients on the immediate docetaxel arm underwent radiologic assessment after cycles two, four and six, while patients in the delayed docetaxel arm the evaluation was performed every three months. Timing and the type of imaging studies used in the Casein kinase 1 control arm has been considered

one of the main limitations of this study, as unfavorably delaying detection of possible disease progression [37]. As it happens in routine daily practice, only about two thirds of patients on the control arm was able to receive second-line docetaxel, as opposed to 95% of patients who received the study drug in the immediate, maintenance arm; thus, the true benefit with “”immediate”" docetaxel in this study could be entirely attributed to the higher proportion of patients receiving active therapy in the maintenance setting. Indeed, a post-hoc analysis documented an identical OS duration of 12.5 months for patients who received docetaxel on either arm of the study, clearly indicating that when patients stop first-line chemotherapy, they should be followed closely to detect progression early and at a time when they remain fit for further treatment [24].