Evaluating the efficacy of fruquintinib versus regorafenib and trifluridine/tipiracil in treating advanced metastatic colorectal cancer: A match-adjusted indirect comparison.

e15550 Background: Fruquintinib (fru), regorafenib (reg), and trifluridine/tipiracil (TAS102) are 3 rd line treatments for patients with previously treated metastatic colorectal cancer (mCRC). Further evidence is required to support clinical decision-making in treating mCRC. In the absence of head-to-head studies, we performed a match-adjusted indirect comparison (MAIC) to evaluate the weighted OS and PFS of fru versus the published OS and PFS of reg and TAS102. Methods: Individual participant-level data (IPD) from FRESCO (NCT02314819) and the published aggregate data (AgD) from the Chinese Subgroup of CONCUR (CONCURsub) (NCT01584830) and TERRA (NCT01955837) were used. According to the eligible criteria of the two AgD trials, 14 IPDs with colon and rectum (6 in fru arm and 8 in placebo arm) were excluded in MAIC with TERRA trial. The baseline covariances of IPD were re-weighted to match those of the AgDs separately. Hazard ratios (HRs) were estimated to compare the weighted OS and PFS of fru with the published OS and PFS of reg or TAS102. Due to the poor overlap of the placebo arms between FRESCO and CONCURsub, unanchored MAIC was conducted to compare fru with reg. Anchored MAIC was performed to compare fru with TAS102. Results: All identified covariances of IPD were well-matched with those of AgDs. The effective sample size (ESS) of IPD after matching and the comparative effect estimates for OS and PFS are presented in the table. Fru showed a numerically favorable weighted OS and a statistically superior weighted PFS versus reg, meanwhile fru had a numerically favorable weighted OS and a statistically superior weighted PFS versus TAS102. Fru showed statistically superior weighted PFS in the male and K-Ras wild-type subgroups versus reg, and in the K-Ras wild-type subgroup versus TAS102. Fru showed favorable weighted OS in < 65 years subgroup versus TAS102. Conclusions: Our analyses showed favorable OS and PFS for fru versus reg and TAS102, as well as beneficial PFS in male versus reg, in K-Ras wild-type subgroup versus reg and TAS102, along with superior OS in < 65 years subgroup versus TAS102, highlighting its therapeutic potential in treating patients with previously treated mCRC. Limitations include the inability to adjust all covariances, biases due to unobserved covariances, and lacking comparison between reg and TAS102 due to unavailable IPDs. The findings should be validated through future RWS. Items MAIC with reg MAIC with TAS102 ESS Fru: 157 (56%), Placebo: 49 (36%) Fru: 218 (80%), Placebo: 81 (62%) OSHR * (95% CI) 0.87 (0.57, 1.3) 0.82 (0.57, 1.19)0.62 (0.41, 0.94), < 65 years subgroup PFSHR * (95% CI) 0.72 (0.57, 0.93)0.50 (0.26, 0.95), male subgroup0.39 (0.2, 0.77), K-Ras wild-type subgroup 0.64 (0.44, 0.94)0.43 (0.26, 0.71), K-Ras wild-type subgroup * The upper limit of 95% CI of HR < 1.0 indicates the comparison statistically favors fru.