Ramucirumab in metastatic renal cell carcinoma: The sex, race, and age issues


In an editorial,[1] Drs. Pal and Figlin made substantial comments regarding the results of the study by Garcia et al from a phase 2 trial of ramucirumab in patients with metastatic renal cell carcinoma (mRCC).[2] We want to add that the sex, race, and age of the patients should not be ignored in future trials of ramucirumab in the treatment of patients with mRCC.

Ramucirumab is a monoclonal antibody vascular endothelial growth factor (VEGF) receptor 2 antagonist. Although the significant association between the expression of VEGF and mRCC is well known, the difference in expression levels of VEGF in serum between men and women has been reported.[3] Renal disease in response to low nephron endowment secondary to intrauterine growth restriction also has been reported to be sex-specific.[4] Thus, the response to ramucirumab is likely sex-specific.

In addition, because VEGF plays a role in angiogenesis and is relevant to the hormone pathway, its expression levels change along with patient age.[5] Furthermore, polymorphism differences in VEGF among ethnic/racial groups has been documented. [6] Together, these differences may potentially influence the differential response to ramucirumab.

Although to our knowledge the data regarding the sex, age, and racial differences in response to treatment with ramucirumab have not been well investigated to date, current evidence has shown the high probability of these differences. We noticed that in the article on ramucirumab monotherapy for previously treated patients with advanced gastric or gastroesophageal junction adenocarcinoma,[7] the hazards ratio for women was 1.431 whereas that for men was 0.676. Thus, the treatment is efficient only for men. In the study of convergent RANK (receptor activator of nuclear factor-kappa B)-mediated and c-Met–mediated signaling components predicting survival among patients with prostate cancer, [8] Hu et al reported that the RANK ligand and neuropilin-1 expression was predictive of survival in white men with prostate cancer, whereas neuropilin-1, nuclear factor-kappa-B (NF-KB)/P65 protein (p-NFκB p65) and VEGF are predictors of overall survival among Chinese men with prostate cancer. We look forward to examining future solid data regarding ramucirumab in the treatment of patients with mRCC.


No specific funding was disclosed.


The authors made no disclosures.

  • Fengxia Liu, MD, NRQingyi Liu, MD, PhDGuiying Wang, MD, MS

  • The Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei, China

  • Weikuan Gu, PhD

  • Department of Orthopedic Surgery, Campbell Clinic and Pathology, University of Tennessee Health Science Center, Memphis, Tennessee