Quality-adjusted time without symptoms or toxicity (Q-TWiST) of nanoliposomal irinotecan (nal-IRI; MM-398) plus 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma (mPAC) patients (pts) previously treated with

[[abstract]]Background: nal-IRI is a nanoliposomal formulation of irinotecan. In the primary analysis of the pivotal NAPOLI-1 Phase-3 trial, nal-IRI+5-FU/LV significantly improved median overall survival (OS, primary endpoint; 6.1 vs 4.2 months, HR = 0.67, P = 0.012) and progression-free survival (PFS; 3.1 vs 1.5 months, HR = 0.56, P = 0.0001) vs 5-FU/LV alone in mPAC pts previously treated with gemcitabine-based therapy. This analysis evaluates between-treatment differences in quality-adjusted survival using a Q-TWiST approach. Methods: Total survival in NAPOLI-1 intent-to-treat cohort over 12 months was partitioned into time with adverse event grade ≥ 3 toxicity (TOX), time in relapse after disease progression (REL), and time without symptoms or adverse event grade ≥ 3 toxicity (TWiST). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility. In the base-case, the utility for TOX (uTOX), REL (uREL) and TWIST (uTWiST) were set to 0.5, 0.5 and 1.0. Nonparametric bootstrapped 95% CIs were derived. The relative Q-TWiST gain of nal-IRI+5-FU/LV vs mean OS for 5-FU/LV was calculated. Threshold analyses varied uTOX and uTWiST between 0.0 and 1.0. Scenario analysis was conducted using per-protocol (PP) population. Results: Nal-IRI+5-FU/LV (n = 117) vs 5-FU/LV (n = 119) pts had significantly more time in TWiST (mean 3.4 vs 2.4 months) and TOX (1.0 vs 0.3 month) but similar time in REL (2.5 vs 2.7 months). In the base-case, nal-IRI+5-FU/LV pts had a 1.3 months (95% CI: 0.4–2.1; 5.1 vs 3.9) greater Q-TWiST (range threshold analyses: 0.9–1.6 months), with a relative Q-TWiST gain of 24% (range threshold analyses: 17%-31%). In the PP population, Q-TWiST was also significantly superior in MM-398+5-FU/LV pts (Q-TWiST gain = 1.8 months; 95% CI: 0.7–3.0). Conclusions: Within NAPOLI-1, combination of nal-IRI+5-FU/LV resulted in statistically significant and clinically important gains in quality-adjusted survival vs 5-FU/LV alone, confirming the clinical outcome benefit of nal-IRI+5-FU/LV in mPAC