CHICAGO—An investigational drug called axitinib is more effective than sorafenib in prolonging progression-free survival (PFS) in patients previously treated for metastatic renal cell carcinoma (mRCC), according to data presented at the 47th Annual Meeting of the American Society of Clinical Oncology.

In a phase 3 study comparing the two agents, median PFS was 6.7 among patients treated with axitinib and 4.7 months among those treated with sorafenib, reported Brian Rini, MD, of the Taussig Cancer Institute at Cleveland Clinic in Ohio.

“These data from the first head-to-head phase 3 study comparing active targeted therapies in advanced RCC are important for clinicians, as they help us advance our understanding of this tumor, where there are limited proven options for previously treated patients,” Dr. Rini said. “The clinically meaningful improvement in PFS seen with axitinib is even more encouraging as it was accompanied by generally manageable tolerability, an important consideration for these patients.”

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Axitinib is an oral selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. VEGF receptors are thought to play a role in the growth and spread of many tumors, including RCC, and breast, lung, thyroid, and colorectal cancer. VEGF receptors 1, 2, and 3 can influence tumor growth, vascular angiogenesis, and metastatic progression of cancer through lymphangiogensis than by inhibiting an individual pathway.

Dr. Rini and his colleagues conducted a randomized, open-label trial comparing the efficacy and safety of axitinib versus sorafenib as second-line therapy for metastatic RCC (mRCC). Eligible patients had clear cell mRCC after first-line systemic therapy with sunitinib, cytokines, bevacizumab, or temsirolimus.

In the study, which was conducted at centers in the United States, Europe, Asia, Canada, Australia, and Latin America, 361 patients received axitinib at a starting dose of 5 mg twice daily and 362 received sorafenib 400 mg twice daily. The study population had a mean age of 61 years and 75% were male. 

Among patients previously treated with sunitinib, median PFS was significant longer in the axitinib recipients than the sorafenib-treated subjects (4.8 vs. 3.4 months). Among patients previously treated with cytokines, median PFS was nearly twice a long in axitinib recipients than sorafenib-treated patients (12.1 vs. 6.5 months).

The objective response rate, which was a secondary study endpoint, was more than double with axitinib compared with sorafenib in the overall patient population (19.4% vs. 9.4%).

“All these drugs are not the same,” Dr. Rini said. “It is important to know there are meaningful differences between these drugs and which ones may be most beneficial in a particular situation. Axitinib was better tolerated than we expected. The patients receiving it had less diarrhea, less rash, and less alopecia [compared with sorafenib recipients], and those are three side effects that are important to patients.”

The most common adverse events that occurred more frequently with axitnib than sorafenib were hypertension (40% vs. 29%), fatigue (39% vs. 32%), dysphonia (31% vs. 14%), and hypothyroidism (19% vs. 8%).  Adverse events found to be more frequent with sorafenib were hand-foot syndrome (27% vs. 51%), rash (13% vs. 32%), alopecia (4% vs. 32%), and anemia (4% vs. 12%).