In ANITA only 50% of patients completed the planned 4 cycles. The ‘fading effect’ of chemotherapy According to the breast or colon cancer models, the benefit of adjuvant treatment may vary over time; the data from NSCLC are conflicting. Long term effect of platinum

based ACT was LY2874455 mw maintained in ANITA after 5 years and in the 7-years (projected) analysis (OS benefit of 8.6% and 8.4%, respectively)[7] and in JBR10 (absolute OS benefit of 11%, after 9.3 years and 12% at 5 years)[9]. However the updated results of CALBG 9633 [13] and IALT [11] did rise many concerns. CALBG 9633 first analysis (at 2.8 years) showed a promising 11% OS increase in stage IB, which lead to early stopping of the study [12]. Unfortunately this was no longer confirmed after the 4.5 [49] and 6 years updates [13]. In the IALT trial (the largest with 1867 patients), the OS benefit after the 90 months analysis was less evident (and RAD001 cell line not statistically significant anymore) in comparison with the analysis performed at 56 months (HR 0.91 and 0.56, respectively). The rate of non-lung cancer related deaths increased by 20%, as compared with the first interim analysis, mostly after 5 years of follow up [11]. Although the unbalanced population taken into account after the 5-years time-point STA-9090 price should to be considered as a randomized comparison, long term

side effects of citotoxic drugs and the high rate of comorbidities in NSCLC patients may partially explain these results [50]. However some differences in classification and reporting of death causes may have influenced the reported outcomes [17]. LACE data show

a sustained effect of ACT over time (survival gain of 3,9% and 5,4% at 3 and 5 years, respectively). Considering only lung cancer-related deaths, the benefit was even higher (+ 6,9% at 5 years), partially outweighed by the higher rate of non lung cancer-related deaths observed in the ACT group. The integration of bio-molecular predictors in the risk assessment process: are they ready for prime time? An effective risk assessment is essential to identify “”high-risk”" stage IB (IA?) patients benefiting from ACT and spare some “”low-risk”" stage II from the toxicities of a treatment not impacting on their OS. Which factors Farnesyltransferase should be considered in this clinical decision process? Clinico-pathological factors Pathological stage is the only prospectively validated prognostic factor to guide the prescription of adjuvant chemotherapy, although based on inadequate prognostic power to stratify patients within the same TNM category [51, 52]. Older age, male gender, poorer PS and non-squamous cell histology are currently known to be associated with decreased survival, although their additional weight to clinical staging does not increase its prognostic power [53].