(Q)-Twist Analysis Of Trastuzumab Plus Fluoropyrimidine/Cisplatin (T-Xp/Fp) Versus Xp/Fp Alone As First-Line Therapy For Advanced Her2-Positive Gastric Cancer

4048 Background: The international, randomized phase III Trastuzumab for Gastric Cancer (ToGA) study has shown that trastuzumab (T) in combination with capecitabine/5-FU and cisplatin (XP/FP) improves overall survival vs. XP/FP alone (median: 13.8 vs. 11.1 mo, HR=0.74, p=0.0046) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) cancer, without impacting on safety. Here we assess the OS gain in the trastuzumab arm, by applying the quality-adjusted time without disease symptoms or treatment toxicity (Q-TWiST) methodology. Methods: The area under the OS curve was partitioned into 3 health states: duration of toxicity (TOX: time spent experiencing grade 3/4 adverse events while in PFS and on study medication), TWiST (PFS minus TOX), and time from progression until end of follow-up or death (REL: OS minus PFS). To exclude treatment bias, clinical follow-up for this analysis was truncated to longest follow-up of the shortest curve (31.3 mo). In a scenario analysis, each health state was utility adjusted per the Q-TWiST methodology. Sensitivity analyses were conducted. Results: No significant difference in time spent in either TOX or REL was observed between arms. Time spent in TWiST was significantly longer for T-XP/FP vs. XP/FP (Table). Overall Q-TWiST results (utility adjusted for treatment toxicities and disease relapse) showed a mean difference of 2.42 mo (95% CI: 1.53–3.25) between treatment arms. Results were confirmed in sensitivity analyses. Conclusions: Per Q-TWiST analysis, the OS gain in HER2-positive advanced gastric or GEJ cancer patients seen with T-XP/FP vs. XP/FP translates into longer PFS without disease symptoms or treatment toxicity. These results confirm earlier findings that the improved OS comes without a negative impact on safety or QoL, which are considered main treatment objectives for advanced gastric cancer. Mean time in each health state by treatment arm, mo (95% CI) Health state XP/FP (n=290) T-XP/FP (n=294) Mean difference PFS 7.07 (6.24–7.89) 9.36 (8.27–10.45) 2.29 OS 13.01 (11.79–14.24) 15.54 (14.24–16.84) 2.52 TOX 2.52 (2.13–2.9) 2.54 (2.10–2.98) 0.02 TWiST 4.55 6.82 2.27 REL 5.95 6.18 0.23 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche