Background: In the Phase III POLO trial (NCT02184195), maintenance olaparib significantly prolonged PFS vs placebo in pts with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and mPaC (median 7.4 vs. 3.8 months). The aim of maintenance treatment is to extend PFS and survival without compromising health-related quality of life due to adverse events. The duration of time spent without symptoms or toxicities (TWiST) and the QA-PFS were assessed in a post hoc analysis of the POLO trial. Methods: Patients were randomized 3:2 to receive maintenance olaparib (tablets; 300 mg bid) or placebo. Restricted mean (RM)-PFS was calculated by estimating the area under the Kaplan–Meier PFS curve between randomization and 29.8 months after randomization (maximum follow-up for the placebo arm in POLO). Patient-centered outcomes were assessed by QA-PFS (derived from the product of the EQ-5D-5L single-index utility score from randomization to disease progression and RM-PFS) and TWiST (RM-PFS minus time with toxicity after randomization). Results: RM-PFS was significantly longer with olaparib, with a between-treatment difference of 4.8 months (P=0.009; Table). Over this period, no significant or meaningful differences in mean EQ-5D-5L index were observed between treatment groups. The corresponding mean QA-PFS was significantly longer with olaparib vs placebo. TWiST analysis demonstrated a benefit with olaparib over placebo (Table): between-arm difference, 3.8 months (P=0.039) for the primary analysis (criteria 1: grade ≥2 nausea, vomiting or fatigue). Sensitivity analysis (criteria 1 plus abdominal pain, diarrhea, decreased appetite or constipation) also revealed a trend toward benefit with olaparib (difference: 3.4 months, P=0.062). Conclusions: Consistent with the primary PFS analysis of the POLO trial, RM-PFS and QA-PFS were significantly longer with maintenance olaparib than with placebo. As demonstrated by the findings of the TWiST analyses, the PFS benefit observed with olaparib in pts with a gBRCAm and mPaC persists even when symptoms of toxicity are considered. Clinical trial information: NCT02184195.

*Higher scores indicate better health status.