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 effects 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.