Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg⁻¹ ipilimumab, and 27 patients treated with 10 mg kg⁻¹ ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22–0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13–0.46; P<0.0001) compared with those with a NLR5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

Background: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. Patients and methods: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m²) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis (FLIE) questionnaires. The main objective was protection from delayed nausea; secondary endpoints included intercycle nausea and nausea anticipatory symptoms. Results: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the 2 arms in the 1st cycle and 2nd cycle. A benefit of ginger over placebo in FLIE nausea score differences (day 6-day 1) was identified for females (P=0.048) and HNC patients (P=0.038) Conclusions: In patients treated with high dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.