Treatment-naive Metastatic Renal Cell Carcinoma Research Articles

Axitinib for the treatment of metastatic renal cell carcinoma.

Renal cell carcinoma is a cancer that results from a genetic inactivation of the VHL tumor suppressor gene leading to an upregulation of VEGF. Targeted therapies against VEGF receptors have piqued substantial interest among clinicians and researchers, and these drugs are now the standard of care in the treatment of advanced renal cell carcinoma. One of these VEGF receptor inhibitors, axitinib, has been shown to be a superior second-line therapy when compared with sorafenib. Although axitinib has clinical activity and a manageable safety profile in patients with treatment-naive metastatic renal cell carcinoma, utility in the front-line setting is area of ongoing investigation. Another area of ongoing research is dose titration of axitinib to achieve the maximum clinical benefit. Interestingly, the axitinib-related side effect of hypertension has shown to be associated with more favorable clinical outcomes. This article describes the development of axitinib and discusses the current indications for clinical use in the management of metastatic renal cell carcinoma.

Axitinib as first-line therapy in metastatic renal cell carcinoma

Axitinib is a highly potent and selective VEGF receptor inhibitor. Previous trials suggested a significant advantage of axitinib versus sorafenib in progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with prior cytokine therapy. Recently an important negative study was reported, which evaluated the PFS with axitinib and with sorafenib in treatment-naive metastatic RCC. This study was underpowered but conveyed an important message on the limit of current VEGF signal targeted drugs as a first-line therapy. In the future, more emphasis should be put on arrangement of dosing and scheduling of drugs already approved as well as development of new agents targeting novel molecules in this disease.

Overall survival (OS) of sorafenib (So) plus interleukin-2 (IL-2) versus So alone in patients with treatment-naive metastatic renal cell carcinoma (mRCC): Final update of the ROSORC trial.

356 Background: A randomized phase II trial evaluating So plus IL-2 versus So alone as first-line treatment of mRCC, did not show any difference in progression-free survival (PFS) (primary endpoint) between the two groups. The final overall survival analysis is here reported. Methods: In this open-label phase II study, 128 patients with mRCC were randomized to receive either oral So 400 mg bid continuous dosing plus IL-2 4.5 MIU subcutaneously administered 5 times weekly for 6 weeks every 8 weeks (Arm A), or So alone (Arm B). At relapse, most patients of the two arms underwent treatment with other targeted therapies (TTs) including sunitinib, everolimus, and axitinib. Overall survival was estimated by Kaplan-Meier method and compared by two-sided log-rank test. Results: According to Motzer criteria 55 % of the patients were low risk in both arms, and 41% and 39% were intermediate risk in Arm A and B respectively. After a median follow-up time of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in Arm A and B, respectively (p = 0.667). Five-year OS was 26.3% (95% CI: 15.9-43.5) for the combination arm and 23.1% (95% CI: 13.2-40.5) for single agent arm. The overall number of death was 85, 42 of whom in the So monotherapy group. Median PFS survival was 7.3 and 6.9 months for Arm A and B, respectively (p = 0.109). Overall, 49 (77%) and 48 (75%) patients in Arm A and B, respectively, received at least one subsequent targeted therapy (TTs). The most common adverse events (AEs) in both arms were asthenia, hand-foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were documented in 38% of patients treated with the combination regimen and in 25% of those undergoing single agent treatment. Conclusions: The OS results suggest an improved outcome in patients with mRCC treated with TTs which appears independent of the treatment initially administered. This prospective study, regarding use of sorafenib in first line of treatment, was associated with a surprising median OS. Clinical trial information: NCT00609401.