A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing lapatinib plus capecitabine compared to capecitabine for metastatic breast cancer (MBC)

1026 Background: Data for this analysis is from a Phase III randomized study that was stopped early by the IDMC since a planned interim analysis demonstrated the primary endpoint had been achieved i.e. longer time to disease progression for patients taking lapatinib plus capecitabine (L+C) versus capecitabine (C) alone. The study included women with refractory advanced or ErbB2+ MBC who had received prior therapy which included anthracyclines, taxanes and trastumuzab. The Q-TWiST method was used to compare the trade-off between toxicities and delayed progression. Methods: The area under overall survival curves for each treatment group was partitioned into three health states: toxicity (TOX), time without toxicity or disease progression (TWiST), and the period until death or end of follow-up following disease progression (REL). TOX is time spent with grade ¾ adverse events (AEs) during progression-free survival (PFS) time. TWiST is the remaining time prior to progression in which no serious AEs were experienced. The utility-weighted sum of the mean health state durations was derived and treatment comparisons of Q-TWiST were made at varying combinations of the utility weights using a threshold utility analysis. Results: The ITT population included 399 subjects ages 26–83 [L+C group N=198, C group N=201]. Overall median survival was 67 weeks based on data through 3APR2006. There was not a significant difference between groups in mean duration of serious AEs prior to progression. (L+C 1.7 weeks, C 1.5 weeks). Using utility weights of 0.5 for both TOX and REL, i.e. counting 2 days of TOX or REL as 1 day of TWiST, resulted in a 7-week difference in quality-adjusted survival favoring L+C (p = 0.0013). The Q-TWiST difference was significant across an entire matrix of possible utility weights. Results were robust in sensitivity analyses including all AEs. An observed-utility analysis based on EQ-5D scores is in progress. Conclusions: The longer time to disease progression with L+C versus C was achieved without increased time with serious AEs, resulting in more quality-adjusted survival for patients. No significant financial relationships to disclose.