Patients with previously treated metastatic colorectal cancer (CRC) experienced significant improvement in quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) when treated with a combination of Fruzaqla (fruquintinib) with best supportive care when compared with treatment via placebo and best supportive care, according to post hoc analysis findings from the phase 3 FRESCO-2 trial presented at the 2024 Gastrointestinal Cancers Symposium.
The mean Q-TWiST was 6.25 months among those in the Fruzaqla arm compared with 4.21 months among patients who received placebo plus best supportive care. Additionally, the mean time from randomization to disease progression with toxicity (TWiST) in each respective arm was 4.06 months versus 1.92 months and the mean time spent with grade 3/4 treatment-emergent side effects between randomization and disease progression (TOX) was 0.45 months versus 0.21 months.
Patients in the Fruzaqla arm had a mean duration of 3.93 months between disease progression and death or censoring (REL) compared with 4.36 months among those in the placebo arm.
Investigators reported consistent improvements in Q-TWiST with the Fruzaqla 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 Fruzaqla arm versus 4.26 months in the placebo arm with a Q-TWIST difference of 2.14 months, representing a 33% relative improvement with Fruzaqla.
“Post hoc Q-TWiST showed that (Fruzaqla) 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,” Dr. Sebastian Stintzing, professor of medicine and head of the department of hematology, oncology and tumor immunology at Charité Universitaetsmedizin Berlin, said during the presentation. “(Fruzaqla) has the potential to provide an improved survival benefit with quality of life (QOL) for patients with previously treated (metastatic) CRC who have limited treatment options.”
The trial’s primary endpoint was overall survival (the time a patient lives following treatment regardless of disease status).
Secondary endpoints included progression-free survival (the time a patient lives without their disease spreading or worsening), objective response rate (patients whose disease responded partially or completely to treatment), disease control rate (patients whose disease disappeared, shrunk or stabilized from treatment), duration of response, safety and health-related QOL.
As part of the post hoc Q-TWiST analysis, investigators divided patient survival time into three 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 side effects that may have affected a patient’s QOL and their ability to tolerate active therapies. For this analysis, Q-TWiST was recalculated using serious side effects rather than grade 3/4 side effects in the TOX health state.
Findings from the FRESCO-2 trial supported the FDA approval of Fruzaqla in metastatic CRC in November 2023. 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 RASwild-type disease who previously received an anti-EGFRtherapy were considered eligible for treatment with Fruzaqla.
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