Axitinib Outperforms Sorafenib in Renal Cell Carcinoma Trial

Brian I. Rini, MD

Axitinib, an oral targeted therapy for advanced renal cell carcinoma (RCC), demonstrated significantly better progression-free survival (PFS) compared with sorafenib in pivotal trial data presented at the ASCO annual meeting Monday.

The AXIS 1032 phase III trial marks the first head-to-head comparison of active targeted therapies in advanced RCC, said lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio.

Pfizer Inc said the European Medicines Agency has agreed to review the drug for approval in second-line settings.

Investigators found that patients in the axitinib arm of the randomized study experienced a median PFS of 6.7 months compared with 4.7 months for those receiving sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals), which equates to a hazard ratio of approximately 0.66 in favor of axitinib.

Additionally, objective response rates were more than doubled with axitinib at 19.4% versus 9.4% for sorafenib.

The study involved 723 patients with clear-cell metastatic RCC whose disease had progressed after prior treatment. Participants were randomized 1:1 to receive either axitinib starting at a dose of 5 mg twice daily or sorafenib at 400 mg twice daily.

Axitinib is a more potent inhibitor of vascular enthothelial growth factor (VEGF) receptors than other VEGF-targeted therapies, Rini said in an interview. He said there currently are 4 other VEGF inhibitors available for RCC, along with 2 drugs that inhibit mammalian target of rapamycin (mTOR).

Despite such options, RCC remains a difficult disease, with 5-year survival rates for patients with advanced RCC of <20%.

“Though there are other choices, none of them are curative,” Rini said. “Not all patients respond. Many can have significant toxicities. While we’re a quantum leap from where we were 10 years ago, there’s still a long way to go. There’s absolutely room for new drug development both along the VEGF front and along other targets as well.”

Rini said the axitinib trial proves the theory that a more powerful VEGF inhibitor can translate to measurably better results.

“Many of us have had a hypothesis that agents that are more potent and selective against the VEGF receptor family, which is the major therapeutic receptor in kidney cancer, would indeed produce clinical benefits,” he said. “Up until now, we haven’t had any comparative data to support or refute that hypothesis.”

Adverse events (AEs) varied between the 2 arms but were considered manageable. Patients treated with axitinib more frequently experienced hypertension, fatigue, dysphonia, and hypothyroidism. In the sorafenib arm, patients most frequently experienced hand-foot syndrome, rash, alopecia, and anemia.

Rini said the AEs were less bothersome to patients treated with axitinib; only 3.9% stopped treatment as a result of toxicities versus >8% for sorafenib.

A substudy in which participants’ quality of life was measured through questionnaires indicated patients using axitinib did not experience a worsening of symptoms when compared with the sorafenib group, according to lead investigator David Cella, PhD, a clinical research specialist and chair of the Department of Medical Social Science at Northwestern University Feinberg School of Medicine in Chicago.

Rini BI, Escudier B, Tomczak P, et al. Axitinib vs sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): results of phase 3 AXIS trial. J Clin Oncol. 2011. (suppl; abstract 4503).

Cella D, Escudier B, Rini B, et al. Patient-reported outcomes (PROs) in a phase 3 AXIS trial of axitinib vs sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC) J Clin Oncol. 2011. (suppl; abstract 4504).