Systemic inflammation and prognosis in patients with RAS/BRAF wild-type metastatic colorectal cancer receiving anti-EGFR therapy: A real-world cohort study

Aim

Colorectal cancer outcomes are heterogeneous, so greater prognostic discrimination is needed. In this retrospective real-world analysis, we assessed the prognostic effect of markers of systemic inflammation in a cohort of patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) who received anti-EGFR therapy during routine care. We further examined the association between these markers and the known predictive biomarkers of anti-EGFR efficacy, amphiregulin (AREG) and epiregulin (EREG).

Method

The prognostic effect of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were tested. The cohort was randomly partitioned into training and validation sets (1:1). Cutoff values were defined in the training set, with analyses repeated in the validation set. The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS), objective response rate and disease control rate.

Results

374 patients with RAS and BRAF wild-type mCRC who received treatment with cetuximab or panitumumab across eight UK centres were included. NLR (≤4 vs >4) and PLR (≤200 vs >200) were independently prognostic for both OS and PFS. SII (≤900 vs >900) gave the strongest prognostic signal (OS: adjusted HR 1.63 [1.26-2.11], P=0.0002 and PFS: adjusted HR 1.62 [1.26-2.08], P=0.0001). There were no associations between NLR or PLR with AREG or EREG, suggesting anti-EGFR benefit in AREG/EREG-high tumours is not related to systemic inflammation.

Conclusion

Routinely assessed markers of systemic inflammation are independently prognostic in patients with mCRC receiving anti-EGFR therapy and may serve as useful adjuncts in informing discussions with patients about prognosis.