A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing lapatinib plus paclitaxel versus paclitaxel alone for first line metastatic breast cancer (MBC) in HER2+ patients.

Abstract

Abstract Abstract #4090 Background: Women with MBC received first line treatment with lapatinib and paclitaxel (L+P) or paclitaxel alone (P) in a phase III randomized, multicenter, double-blind, placebo-controlled study. In a sub-group analysis of HER2+ (ErbB2+) patients, time to tumor progression for L+P was significantly improved, with an emerging trend for survival benefit. The Q-TWiST method was used to examine overall quality-of-life adjusted survival experience comparing the trade-off between treatment toxicities and delayed progression in a subset of the randomized ITT population that overexpressed HER2.
 Methods: Survival curves for each treatment arm were partitioned into 3 health states: TOX (toxicity) - time with grade 3/4 adverse events (AEs) during progression-free survival time; TWiST (time without toxicity or disease progression) - remaining time prior to progression in which no serious AEs were experienced; REL (relapse) - time until death or end of follow-up following disease progression. The utility-weighted sum of the mean health state durations was derived to calculate a Q-TWiST score and treatment comparisons were made at varying combinations of the utility weights using a threshold utility analysis.
 Results: The ITT population included 579 subjects ages 23-87 of which 91 were HER2+ (n = 52 L+P, n = 39 P) based on FISH+ or IHC3+ irrespective of FISH (86 patients based on FISH+ or IHC3+ if FISH unknown; n = 49 L+P, n = 37 P). Overall median survival was 96 weeks after randomization based on data through 5FEB07. For the 91 patient cohort, 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 9.4 week difference (p = 0.0459) in quality-adjusted survival favoring L+P. For the 86 patient cohort the difference was 8.5 weeks still favoring L+P (p = 0.1005). Q-TWiST differences between the arms (for 91 patient cohort) ranged from 5-13 weeks across utility weight combinations, with most tests providing a statistically significant advantage of L+P over P alone. Results from the sensitivity analysis using all grade AEs in the TOX state gave similar results.
 Conclusions: Among HER2+ patients, treatment with L+P resulted in more quality-adjusted survival than with P monotherapy. When utilities for periods of toxicity and relapse were valued at half the utility of TWiST, the Q-TWIST difference was around 9 weeks, approximately 10% of the 96 weeks median overall survival. These findings represent clinically important differences between treatment groups in quality-adjusted survival. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4090.