Clinical significance of sunitinib-associated macrocytosis in metastatic renal cell carcinoma.

Abstract

453 Background: Increases in mean corpuscular volume (MCV) and hypothyroidism have been observed in patients on sunitinib treatment. We characterized tyrosine kinase-associated macrocytosis in metastatic renal cell carcinoma (mRCC) patients and its relationship, along with thyroid dysfunction, to progression-free survival (PFS). Methods: A retrospective chart review was performed on patients treated with sunitinib and/or sorafenib (01/2005-01/2011). Data pertaining to the development of macrocytosis was analyzed in association with our previous data on thyroid dysfunction in these patients. We assessed PFS, as clinically defined by the treating provider. Results: Seventy-four patients with 103 treatment periods for sorafenib (47) and sunitinib (56) were analyzed. Macrocytosis was found in 55% and 8% of sunitinib and sorafenib treatment periods, respectively (p<0.001). Focusing on the sunitinib-treated patients for all further analysis, the median PFS was 11 months (mo) (95% CI, 6-19). Median PFS was 21 mo (95% CI, 11-25) for patients who developed macrocytosis compared to 4 mo (95% CI, 3-8) in normocytic patients (p=0.0001). The time to development of macrocytosis did not affect the degree of macrocytosis observed (p=0.47). Macrocytosis and hypothyroidism were both significant predictors of prolonged PFS in our cohort. The greatest difference in PFS was noted between patients who developed both macrocytosis and hypothyroidism (25 mo) versus those who remained both normocytic and euthyroid (5 mo) (p<0.0001). Conclusions: Sunitinib-related macrocytosis is associated with a prolonged PFS in mRCC. The concurrent development of both hypothyroidism and macrocytosis in this setting was associated longer PFS compared to either alone. Increased MCV may be used as a biomarker for sunitinib response in this setting. [Table: see text]