The final multivariate analysis showed seven independent negative markers for PFS: baseline CAR > 0.51 (HR = 1.643, p = 0.003), NLR > 1.28 (HR = 2.017, p = 0.002), LDH > 250 U/L (HR = 1.345, p = 0.027), NSE > 16.3 ng/mL (HR = 1.827, p = 0.003), hyponatremia (HR = 1.483, p = 0.017), SD + PD for the best efficacy to first‐line chemotherapy (HR = 2.045, p < 0.001), and extensive stage (HR = 2.146, p < 0.001) . This evidence concerns the gene ENO2 and Hyponatremia.