Peri- or post-operative chemotherapy benefits patients with resectable CRCLM

Administering chemotherapy to patients with resectable colorectal cancer liver metastases (CRCLM) significantly reduced the risk of recurrence and was associated with better overall survival in an analysis of individual patient data from 4 phase 3 trials.

The liver is the most frequent site of metastatic spread of CRC. 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. The relatively small available sample size of randomised phase 3 studies precludes meaningful survival analyses in the entire population and specific subgroups.

To get more insight into the value of post-operative or peri-operative systemic chemotherapy in patients with CRCLM, individual patient data (IPD) was collected from 3 randomised phase 3 trials investigating post-operative chemotherapy (i.e. FFCD-ACHBTH-AURC 9002, ENG [EORTC/NCIC CTG/GIVIO], and UMINC000000013) and 1 randomised phase 3 trial investigating peri-operative chemotherapy (EORTC 40983), with a total of 821 participants [1–4]. The primary endpoint of the IPD analysis was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and survival outcomes in pre-specified subgroups. Dr Giacomo Bregni (Brussels University Hospital, Belgium) presented the results [5].

Of all patients included in the analysis, 411 had undergone surgery alone and 410 had undergone surgery and chemotherapy. A statistically significant difference in median DFS was observed between cohorts: 1.2 versus 1.9 years in the surgery alone and chemotherapy cohort, respectively (HR 0.79; 95% CI 0.67–0.93; P=0.004). DFS benefit for chemotherapy was maintained after leaving out IPD from the peri-operative trial. A trend was observed for a better median OS in the chemotherapy cohort (HR 0.82; 95% CI 0.68–1.00; P=0.048 in all trials; HR 0.77; 95% CI 0.58–1.02; P=0.063 in post-operative trials).

Analysis of pre-planned subgroups showed a significant improvement of DFS both in patients with normal alkaline phosphatase levels (P=0.026 vs raised levels) and patients with synchronous metastases (P=0.036 vs metachronous metastases). However, no significant improvement in OS was observed in any subgroup.

“This largest IPD meta-analysis to date shows that administering chemotherapy to patients with resectable CRCLM significantly reduces the risk of recurrence and is associated with better OS,” Dr Bregni concluded. Patients with synchronous liver metastases or normal alkaline phosphatase levels may benefit most from chemotherapy.

1. Portier G, et al. J Clin Oncol. 2006;24:4976-4982.
2. Langer B, et al. Proc Am Soc Clin Oncol 2002;21:149a.
3. Hasegawa K, et al. PLoS One 2016;1(9):e0162400.
4. Nordlinger B, et al. Lancet Oncol. 2013;14:1208-1215.
5. Bregni G, et al. Individual patient data (IPD) meta-analysis of randomised phase III trials (RP3) of chemotherapy for resectable colorectal cancer liver metastases (CRCLM): EORTC RP-2145. Abstract 5MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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Posted on 21 August 202421 August 2024