16P High fibrinogen levels affect the clinical outcomes of nivolumab in the second-line treatment of metastatic renal cell carcinoma patients: A prospective cohort study

A number of coagulation-related studies found that fibrinogen was elevated in renal cell carcinoma (RCC) patients and correlated with more advanced disease. The impact of hyperfibrinogenemia on the clinical outcomes of immunotherapy remains uncertain. In this prospective cohort study, fibrinogen levels were measured one week prior to the second-line nivolumab therapy (240 mg or 480 mg every 2 or 4 weeks) and then monthly until disease progression or unacceptable toxicity. High fibrinogen level was defined as = >5 g/L. Key eligibility criteria included metastatic clear cell RCC resistant to the first-line targeted therapy, <= 3 MSKCC risk factors, ECOG PS 0-2, platelet count <400×10(9)/L, no heart diseases, no anticoagulation therapy, and age 40-65 years. The primary endpoint was overall survival (OS) in cohorts with high (H) and normal (N) fibrinogen levels. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and fibrinogen levels during therapy. Between November 2018 and January 2021, 82 patients were enrolled, of whom 41 and 41, respectively, were recruited in H and N cohorts. The groups were well balanced at baseline. The median follow-up time was 32.4 months. Compared to patients in N cohort, patients in H cohort had shorter OS (P=0.001), shorter PFS (P<0.01), and lower ORR (P=0.012). In H cohort, a below-median fibrinogen level was associated with longer observed OS (median, 23.7 vs. 19.4 months; P=0.03). In N cohort, 6 (15%) patients with stable disease had an increase in fibrinogen levels during nivolumab therapy. The table summarizes patients’ characteristics and clinical outcomes.Table: 16PH cohort, N=41N cohort, N=41Age (years), mean (range)59 (40-65)62 (43-65)MSKCC risk factors, N (%) 2 335 (85) 6 (15)33 (80) 8 (20)ECOG PS, N (%) 0-1 229 (71) 12 (29)28 (68) 13 (32)First-line therapy, N (%) Sunitinib Pazopanib Others24 (59) 10 (24) 7 (17)21 (51) 15 (37) 5 (12)Fibrinogen (baseline), g/L, mean (SD)6.4 (5.1-8.4)2.9 (1.8-3.7)OS, median (95% CI)20.2 (17.4-25)31.5 (26.8-NR)PFS, median (95% CI)4.0 (2.9-5.1)9.4 (5.5-14.1)ORR, N (%)7 (17)13 (32) Open table in a new tab Detection of high baseline levels of fibrinogen in plasma derived from patients with metastatic RCC may be associated with poor clinical outcomes with nivolumab. These findings require large-scale prospective validation.