Fruquintinib Plus BSC Provides Clinically Meaningful Quality-Adjusted Survival Benefit Vs BSC Alone in mCRC

Fruquintinib (Fruzaqla) combined with best supportive care (BSC) showcased a clinically meaningful improvement in quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) vs BSC alone in patients with previously treated metastatic colorectal cancer (mCRC) enrolled in the phase 3 FRESCO-2 trial (NCT04322539), according to data from a post-hoc analysis presented at the 2024 Gastrointestinal Cancers Symposium.¹

The mean Q-TWiST was 6.25 months (95% CI, 5.89-6.61) among those in the fruquintinib arm compared with 4.21 months (95% CI, 3.81-4.60) among patients who received placebo plus BSC(difference, 2.04; 95% CI, 1.51-2.57; P <.05). Additionally, the mean time from randomization to disease progression with toxicity (TWiST) in each respective arm was 4.06 months (95% CI, 3.75-4.36) vs 1.92 months (95% CI, 1.75-2.10; difference, 2.14; 95% CI, 1.78-2.49; P <.05), and the mean time spent with grade 3/4 treatment-emergent adverse effects (TEAEs) between randomization and disease progression (TOX) was 0.45 months (95% CI, 0.37-0.53) vs 0.21 months (95% CI, 0.15-0.28; difference, 0.24; 95% CI, 0.13-0.34; P <.05).

Patients in the fruquintinib arm had a mean duration of 3.93 months (95% CI, 3.55-4.32) between disease progression and death or censoring (REL) compared with 4.36 months (95% CI, 3.75-4.96) among those in the placebo arm (difference, –0.43; 95% CI, –1.15 to 0.29; P ≥.05).

Investigators reported consistent improvements in Q-TWiST with the fruquintinib combination across all patient subgroups apart from those with unknown primary tumor sites and those with right- and left-sided tumors. These outcomes were attributed to a very small number of patients within these subgroups. Based on a sensitivity analysis, the mean duration of Q-TWiST was 6.41 months in the fruquintinib arm vs 4.26 months in the placebo arm with a Q-TWIST difference of 2.14 months (95% CI, 1.61-2.68; P <.05), representing a 33.0% relative improvement with fruquintinib.

“Post-hoc Q-TWiST showed that fruquintinib delays disease progression and prolongs patient survival without substantially increasing toxicity, which is particularly notable when considering the toxicity was evaluated against an inactive comparator,” Sebastian Stintzing, MD, professor of medicine and head of the Department of Hematology, Oncology, and Tumor Immunology at Charité Universitaetsmedizin Berlin, said during the presentation. “Fruquintinib has the potential to provide an improved survival benefit with quality of life [QOL] for patients with previously treated mCRC who have limited treatment options.”

In the FRESCO-2 trial, 691 patients with mCRC from North America, Europe, Japan, and Australia were randomly assigned 2:1 to receive fruquintinib at 5 mg orally (n = 461) or matched placebo (n = 230) plus BSC as part of a 3-weeks-on, 1-week-off 28-day cycle.

The trial’s primary end point was overall survival. Secondary end points included progression-free survival, objective response rate, disease control rate, duration of response, safety, and health-related QOL.

As part of the post hoc Q-TWiST analysis, investigators divided patient survival time into 3 health states: TOX, TWiST, and REL. Investigators calculated Q-TWiST as the utility-weighted sum of the mean durations of each of the previously described health states. Additionally, Kaplan-Meier estimates were used to determine the mean time spent in these health states for each treatment arm.

The study also included a sensitivity analysis to account for serious AEs that may have affected a patient’s QOL and their ability to tolerate active therapies. For this analysis, Q-TWiST was recalculated using serious TEAEs rather than grade 3/4 TEAEs in the TOX health state.

Findings from the FRESCO-2 trial supported the FDA approval of fruquintinib in mCRC in November 2023.² Specifically, the approval extended to those who received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy plus an anti-VEGF agent. Additionally, those with RAS wild-type disease who previously received an anti-EGFR therapy were considered eligible for treatment with fruquintinib.

References

1. Stintzing S, Tabernero J, Satoh T, et al. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial. J Clin Oncol. 2024;42(suppl 3):116. doi:10.1200/JCO.2024.42.3_suppl.116
2. Takeda receives US FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed January 20, 2024. https://www.takeda.com/newsroom/newsreleases/2023/Takeda-Receives-US-FDA-Approval-of-FRUZAQLA-fruquintinib-for-Previously-Treated-Metastatic-Colorectal-Cancer/