Presentation Authors: Anup Patel*, London, United Kingdom, Alain Ravaud, Bordeaux, France, Robert Motzer, New York, NY, Allan Pantuck, Los Angeles, CA, Michael Staehler, Munich, Germany, Bernard Escudier, Villejuif, France, Jean-François Martini, La Jolla, CA, Mariajose Lechuga, Milan, Italy, Xun Lin, La Jolla, United Kingdom, Daniel George, Durham, NC
Introduction: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are reported to predict clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). Adjuvant sunitinib (SU) significantly improved disease-free survival (DFS) vs placebo (PBO) in patients with loco-regional RCC at high risk of recurrence post nephrectomy (S-TRAC trial). This study aimed to evaluate NLR and PLR as potential prognostic factors in high-risk loco-regional non-metastatic RCC.
Methods: Post-hoc exploratory analysis of the high-risk S-TRAC trial patients. Kaplan-Meier estimates and Cox proportional analyses were performed on baseline and change from baseline at Week 4 NLR and PLR to assess their association with DFS. P-values were two-sided and based on an unstratified log-rank test.
Results: 609/615 patients had NLR and PLR baseline values; 574 patients had paired values at both baseline and at Week 4. Cut-off values were defined as NLR < 3 vs â‰¥3 and PLR < 140 vs â‰¥140, based on ROC curves. The significantly shorter DFS of baseline NLR < 3 vs NLR â‰¥3 in PBO patients (HR 0.63, P=0.04), was eliminated by SU treatment (HR 0.91, P=0.67). SU Patients with baseline NLR < 3 had significantly longer DFS vs PBO (median DFS 7.1 vs 4.7 years; HR 0.71, P=0.02); however, DFS was similar regardless of treatment for baseline NLR â‰¥3 (HR 1.03, P=0.91). No statistically significant differences in DFS were observed for baseline PLR ( < 140 vs â‰¥140) in the overall (HR 0.91, P=0.45), SU (HR=0.83, P=0.33) or PBO (HR=0.97, P=0.87) population; however, there was a trend toward longer DFS in SU patients with baseline PLR < 140. Overall, a â‰¥25% decrease in NLR or PLR at Week 4 was associated with longer DFS vs no change (NLR, HR 0.71 [P=0.01]; PLR, HR 0.76 [P=0.05]). A greater proportion of patients had a â‰¥25% decrease in NLR or PLR at Week 4 when treated with SU (NLR, n=200 [71.2%]; PLR, n=175 [62.3%]) vs PBO (NLR, n=51 [17.4%]; PLR, n=43 [14.7%]). Patients with â‰¥25% decrease in NLR or PLR at Week 4 continued on to receive a higher median cumulative dose of SU (NLR 10137.5 mg; PLR 9856.3 mg) vs those with no change (NLR 8168.8 mg; PLR 9418.8 mg) or â‰¥25% increase (NLR 6712.5 mg; PLR 6425.0 mg).
Conclusions: Low baseline NLR, and a â‰¥25% decrease in NLR or PLR after 4 weeks, could both be early predictors of those high-risk patients most likely to benefit from adjuvant SU. NLR and PLR changes at Week 4 appeared to separate those most likely to tolerate and respond to adjuvant SU, eliminating potential toxicity risk in those least likely to benefit.
Source of Funding: Pfizer Inc.