Prognostic and predictive value of baseline derived neutrophil-to-lymphocyte ratio (dNLR) in <i>RAS</i> wild-type (WT) metastatic colorectal cancer (mCRC) receiving 5-fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) maintenance: A post-hoc analysis of the PANAMA/AIO KRK 0212) trial.

Abstract

e15552 Background: The derived neutrophil-to-lymphocyte ratio (dNLR) is an established prognostic marker in solid tumors including metastatic colorectal cancer (mCRC), but its predictive value remains unclear. The dNLR was evaluated as a prognostic biomarker and as a potential predictor of treatment outcome during fluorouracil/folinic acid (FU/FA) ± panitumumab (pmab) maintenance therapy in patients with RAS wild-type mCRC enrolled in the PANAMA trial (NCT01991873). Methods: Patients with available baseline blood counts prior to induction therapy were grouped according to dNLR using a predefined cut-off of 2.2. Progression-free survival (PFS) and overall survival (OS) from initiation of maintenance therapy, as well as PFS of reinduction therapy, were estimated using the Kaplan–Meier method and compared by log-rank testing and Cox proportional hazards regression. Multivariable Cox models adjusted for confounders were used to assess independent prognostic effects. Predictive effects were evaluated using interaction tests within Cox proportional hazards models for maintenance and reinduction. Results: Of 241 patients included into the full analysis set with available data, n = 140 had baseline dNLR ≤2.2 and n = 101 dNLR &gt; 2.2. While median PFS during maintenance therapy did not differ according to baseline dNLR (dNLR ≤2.2 vs. &gt; 2.2: 10.1 vs. 9.7 months; log-rank p = 0.25), OS was significantly longer in patients with dNLR ≤2.2 (30.8 vs 22.7 months; log-rank p &lt; 0.001). Baseline dNLR remained independently associated with OS in multivariable Cox regression (HR 1.56, 95% CI 1.15–2.12; p = 0.004). Despite numerical prolongation of PFS and OS during maintenance therapy by the addition of pmab to FU/FA, no significant interaction between baseline dNLR and maintenance treatment arms was observed (PFS (maintenance): dNLR ≤2.2 = 8.8 vs 5.6 months; dNLR &gt; 2.2 = 9.7 vs 5.8 months; interaction p = 0.72; OS: dNLR ≤2.2 = 33.7 vs 28.2 months; dNLR &gt; 2.2 = 26.1 vs 20.1 months; interaction p = 0.294). By contrast, PFS after treatment reinduction was significantly shorter after FU/FA + pmab compared with FU/FA maintenance in patients with dNLR ≤2.2, whereas no difference according to prior maintenance treatment was observed in patients with dNLR &gt; 2.2 (dNLR ≤2.2 = 2.6 vs 7.4 months; dNLR &gt; 2.2 = 5.8 vs 6.2 months; interaction p = 0.036). Conclusions: Baseline dNLR is an independent prognostic biomarker for OS in patients with RAS WT mCRC treated within the PANAMA trial. Potential information might be derived for the optimal choice of maintenance and reinduction strategies.