Abstract 60P
Background
The objective of this study was to estimate the relative treatment (TRT) effects of trifluridine/tipiracil (FTD/TPI) + bevacizumab (BEV) versus (vs) other interventions for patients in third-line (3L) TRT for refractory metastatic Colorectal Cancer (mCRC) through systematic literature review (SLR) and network meta-analysis (NMA).
Methods
We conducted a search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, Ovid and clinical trial registries from January 1, 2010, to October 12, 2023, to include randomized clinical trials (RCTs), non-randomized, and open-arm trials of 3L TRTs for mCRC. A feasibility assessment for performing the NMA of overall survival (OS) and progression-free survival (PFS) was conducted to determine whether the RCT evidence for the interventions formed one network for each population and outcome of interest. The results of the RCTs identified in the SLR were synthesized through both fixed and random effect NMAs for OS and PFS.
Results
From 19 RCTs identified, 16 trials were connected in a network with FTD/TPI + Bev (8 TRT regimens for OS and 9 for PFS). The results of the fixed effect model are shown in the table. Similar results were observed with the random effect model; FTD/TPI + Bev was numerically and/or statistically superior in terms of OS and PFS vs 3L TRT (except for CETU + IRI + BEV). Table: 60P
| Fixed Effect | FTD/TPI + Bev vs | FTD/TPI | CETU | CETU + IRI | PANI | CETU + IRI+ Bev | Regorafenib | Fruquintinib | FTD/TPI + PANI | Placebo/BSC |
| OS | HR | 0.59 | 0.47 | 0.45 | 0.47 | 1.09 | 0.59 | 0.63 | 0.57 | 0.42 |
| 95% CI | 0.49 0.73 | 0.36 - 0.62 | 0.23 - 0.85 | 0.36 - 0.62 | 0.33 - 3.59 | 0.44 - 0.79 | 0.48 - 0.83 | 0.31 - 1.05 | 0.33 - 0.53 | |
| PFS | HR | 0.45 | 0.32 | 0.24 | 0.34 | 0.37 | 0.46 | 0.7 | 0.95 | 0.21 |
| 95% CI | 0.38 - 0.54 | 0.25 - 0.42 | 0.12 - 0.45 | 0.26 - 0.45 | 0.12 - 1.17 | 0.35 - 0.60 | 0.54 - 0.91 | 0.53 - 1.66 | 0.17 - 0.26 |
IRI = Irinotecan, CETU = Cetuximab, PANI = Panitumumab, results in bold = Statistically significant.
Conclusions
FTD/TPI + BEV demonstrated significant efficacy improvement in terms of OS and PFS vs the majority of 3L TRTs, in both fixed and random effects models supporting the use of this combination for mCRC patients in 3L.
Legal entity responsible for the study
Servier.
Funding
Servier.
Disclosure
J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Expert Testimony: Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, steering committee of clinical trial: Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD); Non-Financial Interests, Other, steering committee of clinical trials: Pfizer, Servier. S. Yahiaoui, E. Choucair, W. Yao, O. Hauch: Financial Interests, Personal, Full or part-time Employment: Servier.