5MO - Individual patient data (IPD) meta-analysis of randomised phase III trials (RP3) of chemotherapy for resectable colorectal cancer liver metastases (CRCLM): EORTC RP-2145

Background

The optimal management of resectable CRCLM remains a matter of debate, and practice in this setting is highly heterogeneous. In particular, the value of post-operative or peri-operative systemic chemotherapy is uncertain, and the relatively small sample size of the available RP3 precludes meaningful survival analyses in the entire population and specific subgroups.

Methods

We conducted a systematic review and meta-analysis of RP3 trials testing surgery plus systemic chemotherapy (given either post-operatively or peri-operatively) versus surgery alone in patients with resectable CRCLM. IPD from the retrieved and accessible trials were pooled in a central database. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and survival outcomes in pre-specified subgroups. The study is sponsored by the EORTC.

Results

IPD from 4 RP3 trials (EORTC 40983, FFCD-ACHBTH-AURC 9002, ENG, UMIN C000000013) were collected. Pooling data from the post-operative chemotherapy studies (FFCD, ENG, UMIN C000000013) (n=457), a significant difference in terms of DFS (HR 0.77; 95% CI: 0.61-0.96; p=0.020) and a trend for OS (HR 0.78; 95% CI: 0.59-1.03; p=0.076) were observed in favour of the chemotherapy arm. 3-year DFS were 41% and 35%, while 5-year OS were 58% and 52% in the chemotherapy and surgery alone arm, respectively. Pooling these data with those from trials testing a peri-operative chemotherapy strategy (EORTC 40983) (n=821), a significant benefit for PFS (HR 0.79; 95% CI: 0.67-0.93; p=0.004) and a trend for OS (HR 0.83; 95% CI: 0.68-1.00; p=0.052) were confirmed. 3-year DFS were 40% and 33%, while 5-year OS were 55% and 50% in the chemotherapy and surgery alone arm, respectively.

Conclusions

This is the largest IPD meta-analysis to date in this setting. Administering systemic chemotherapy (either post-operatively or peri-operatively) to patients with resectable CRCLM reduces significantly the risk of recurrence/progression or death, and is associated with a trend towards a better OS. Further results, including survival outcomes in specific subgroups, will be presented at the meeting.

Legal entity responsible for the study

European Organisation for Research and Treatment of Cancer (EORTC).

Funding

European Organisation for Research and Treatment of Cancer (EORTC).

Disclosure

N. Kokudo: Financial Interests, Personal, Other, Steering committee member for a clinical trial: AstraZeneca. T. Aparicio: Financial Interests, Personal, Invited Speaker, 2022: Servier; Financial Interests, Personal, Invited Speaker, 3 Conferences: Pierre Fabre; Financial Interests, Personal, Advisory Board, 2 Board in 2022 and 2023: BMS; Financial Interests, Personal, Invited Speaker, 1 conference: MSD; Non-Financial Interests, Leadership Role, 2021-2024: Fédération Francophone de Cancérologie Digestive. F. Sclafani: Financial Interests, Personal, Advisory Board: AMAL Therapeutics, Bayer, BMS, Dragonfly Therapeutics, GSK, Nordic Pharma, Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck, Servier; Financial Interests, Institutional, Research Grant: Amgen, Astellas, AstraZeneca, Bayer, BMS, Merck, MSD, Pierre Fabre, Roche, Sanofi; Non-Financial Interests, Leadership Role, Secretary of the EORTC Gastrointestinal Tract Cancer Group: EORTC Gastrointestinal Tract Cancer Group; Other, Travel grants: Amgen, Bayer, Lilly, Merck, Roche, Servier. All other authors have declared no conflicts of interest.