Abstract 400P
Background
Previous network meta-analyses (NMA) showed favorable overall survival (OS), progression-free survival (PFS), and safety profiles for regorafenib dose optimization (rego 80+) compared to best supportive care (BSC), regorafenib standard dosing (rego 160), and trifluridine/tipiracil (TAS) in the treatment of relapsed/refractory mCRC. This update adds fruquintinib (fruq) as a comparator.
Methods
Randomized controlled trials (RCTs) included in the NMA were identified via a systematic literature review. Fixed and random effect Bayesian and frequentist Bucher NMAs were used to synthesize hazard ratios (HRs) for OS and PFS, and odds ratios for adverse events (AEs). The NMA HRs were applied to the rego 80+ Kaplan-Meier curves from the ReDOS trial to estimate predicted median OS (mOS) and PFS of each treatment.
Results
Seven RCTs were included in the updated NMA (ReDOS, CORRECT, CONCUR, RECOURSE, TERRA, Yoshino 2012, and FRESCO). Findings were consistent across Bucher and Bayesian models. Rego 80+ was favorable in OS vs all comparators with a risk reduction of >50% and >3 months gain in mOS vs BSC (statistically significant), and ∼30% risk reduction and >2 months gain in mOS vs rego 160, TAS, and fruq (Table). Rego 80+ was favorable in PFS vs all comparators except fruq. For grade 3+ AEs, rego 80+ was favorable vs fruq in hypertension and comparable in other reported AEs; both had higher hand-foot skin reactions than TAS, but TAS had the highest hematological toxicities including anemia, neutropenia, febrile neutropenia, and leukopenia. Table: 400P
Bucher NMA results for overall survival and predicted medians
| Interventions | HR [95% CI] for Rego 80+ vs comparator | Median OS [95% CI] months |
| Rego 80+ | reference | 9.8 [7.5, 11.9] |
| BSC | 0.48 [0.28, 0.82] | 6.4 [2.3, 11.1] |
| Rego 160 | 0.72 [0.41, 1.27] | 7.5 [4.6, 11.9] |
| TAS | 0.69 [0.40, 1.20] | 7.5 [4.2, 12.6] |
| Fruq | 0.74 [0.41, 1.33] | 7.7 [4.2, 13.5] |
Conclusions
Findings from this NMA indicate that rego 80+ is superior in OS to all other comparators. Its safety profile was mostly comparable to fruq, and offered advantages to TAS in terms of lower hematological toxicities. Given these findings, rego 80+ could be considered a favored treatment option for patients with relapsed/refractory mCRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
H. Ostojic: Financial Interests, Institutional, Full or part-time Employment: Bayer. L. Gaianu: Financial Interests, Institutional, Full or part-time Employment: Bayer. Y. Su: Financial Interests, Institutional, Full or part-time Employment: Bayer. All other authors have declared no conflicts of interest.