Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60–80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin. Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: “cases” developed oxaliplatin-induced grade 3–4 neuropathy (n = 48), and “controls” (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated. We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16–0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673. SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.

Background/Objectives: Anti–PD-1/PD-L1 blockers have revolutionized the treatment landscape of non–small cell lung cancer (NSCLC) lacking oncogene-addicted alterations, particularly in tumors with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%). Cemiplimab is approved as first-line monotherapy in this setting. However, real-world data remain scarce. This study aimed to evaluate the efficacy and safety of single-agent cemiplimab in a multicenter Spanish cohort and compare outcomes with a historical pembrolizumab cohort. Methods: Cemi-SPA is a retrospective multicenter study including 150 patients with advanced NSCLC and PD-L1 ≥ 50% treated with cemiplimab as first-line monotherapy across 21 Spanish centers. Clinical outcomes were analyzed and compared with a historical cohort of 144 patients treated with pembrolizumab. Propensity score matching (PSM) was performed to adjust for baseline differences. Results: Median progression-free survival (PFS) and overall survival (OS) were 8.1 and 12.6 months, respectively. ECOG performance status ≥ 2 was independently associated with worse outcomes, whereas the development of immune-related adverse events correlated with improved PFS and OS. After PSM, no significant differences were observed between cemiplimab and pembrolizumab in terms of efficacy. Conclusions: Cemiplimab demonstrated comparable real-world efficacy and safety to pembrolizumab in patients with advanced NSCLC and PD-L1 ≥ 50%. ECOG performance status emerged as the strongest prognostic factor, highlighting the importance of patient selection in routine clinical practice.