Health-related quality of life (HRQoL) associated with fruquintinib in the global phase 3, placebo-controlled, double-blind FRESCO-2 study.
Authors: Sobrero Alberto F. , Dasari Arvind , Lonardi Sara , Garcia-Carbonero Rocio , Elez Elena , Yoshino Takayuki , Yao James C. , Garcia-Alfonso Pilar , Kocsis Judit , Cubillo Antonio , Sartore-Bianchi Andrea , Satoh Taroh , Randrian Violaine , Tomasek Jiri , Chong Geoff , Yang Zhao , Schelman William R. , Kania Marek K. , Tabernero Josep , Eng Cathy 
Published: January 2023

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Background: The global phase 3 FRESCO-2 study, (NCT04322539) demonstrated that fruquintinib (F) vs placebo (P) significantly improved OS (HR=0.66 [95% CI: 0.55-0.80]; p<0.001) and PFS (HR=0.32 [95% CI: 0.27-0.39]; p<0.001) in heavily pre-treated patients (pts) with refractory metastatic colorectal cancer (mCRC). F safety profile was consistent with the established monotherapy profile. Here we report the HRQoL and tolerability results. Methods: Pts were randomized 2:1 to F + BSC or P + BSC. EORTC QLQ-C30 and EQ-5D-5L were assessed at baseline and on Day (D) 1 of each Cycle (C) until treatment discontinuation, and ECOG PS was assessed at baseline, D1 of each C, and D21 of C1 to C3. Least-squares mean (LSM) change from baseline to post-baseline visits and the difference between F and P in QLQ-C30 scale scores (e.g. global health status [GHS]/QoL) and EQ-5D-5L scale scores (e.g. visual analog scale [VAS]) were calculated using mixed model repeated measures approach. For each scale, the appropriate minimally important difference (MID) thresholds were determined to evaluate the improvement or deterioration. Time to deterioration (TTD), defined as worsening from baseline in scale-specific MID or death, was analyzed using Kaplan-Meier method, adjusted log-rank test, and stratified Cox PH model. QLQ-C30 and EQ-5D-5L analyses were conducted on the ITT population, and ECOG PS was on the safety population. Results: 691 pts were randomized (F: 461 vs P: 230) and 686 pts received study drug (F: 456 vs P: 230). Median treatment Cycles received (range) were 3 (1, 20) for F vs 2 (1, 13) for P. More than 79% of pts on both arms had a baseline and ≥1 post-baseline assessment for QLQ-C30, EQ-5D-5L, and ECOG PS. GHS/QoL was similar between F and P at baseline; the LSM differences between F and P were 1.7 (95% CI: -1.7, 5.0) for C2 and 1.6 (95% CI: -3.2, 6.4) for C3. At C4, <30 P patients were available. The % of patients who remained stable (MID -6.38 to <8.43) or improved (≥8.43) was numerically higher for F vs P (C2: 61.5% vs 57.1%; C3: 56.4% vs 50.9%). Median TTD was 2.1 months in F and 1.8 months in P (HR=0.9; 95% CI: 0.7-1.0; P=0.098). EQ-5D VAS was similar between F and P at baseline; the LSM differences between F and P were 0.6 (95% CI: -2.3, 3.5) for C2 and 1.4 (95% CI: -2.8, 5.6) for C3. The % of patients who remained stable (MID -7 to <7) or improved (≥7) was similar for F and P (C2: 64.6% vs 58.3%; C3: 64.2% vs 64.8%). Median TTD was 2.6 months in F and 1.9 months in P (HR=0.8; 95% CI: 0.6-0.9; P=0.001). The % of patients with ≥1-point increase from baseline in ECOG PS was 52.1% in F vs 54.0% in P. Conclusions: HRQoL is not negatively impacted by treatment with F. TTD in health utility instrument EQ-5D is improved for patients receiving F. These results, along with improved OS and PFS and favorable toxicity profile, further support F as a potential new treatment option for patients with refractory mCRC. Clinical trial information: NCT04322539 .