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Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3
Brian I Rini1, Bernard Escudier, Piotr Tomczak
1Cleveland Clinic Taussig Cancer Institute, Main Campus, Euclid Avenue, Cleveland, OH 44195, USA. rinib2@ccf.org
Background:
The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer.
Methods:
We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392.
Findings:
A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib (hazard ratio 0·665; 95% CI 0·544-0·812; one-sided p<0·0001). Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm.
Interpretation:
Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma.
Funding:
Pfizer Inc.
Insights
Axitinib significantly improved progression-free survival (PFS) in patients with advanced renal cell carcinoma compared to sorafenib. This study positions axitinib as a valuable second-line treatment option for this condition.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced renal cell carcinoma (RCC) treatment has been transformed by anti-angiogenic targeted therapies.
- No prior phase 3 trials have directly compared different targeted agents in RCC.
Purpose of the Study:
- To compare the efficacy of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma.
- To evaluate progression-free survival (PFS) as the primary endpoint.
Main Methods:
- A randomized phase 3 trial involving 723 patients with advanced RCC who progressed on first-line therapy.
- Patients were assigned to receive either axitinib or sorafenib.
- Progression-free survival (PFS) was assessed by independent radiology review.
Main Results:
- Axitinib demonstrated a median PFS of 6.7 months, compared to 4.7 months for sorafenib (Hazard Ratio 0.665; p<0.0001).
- Discontinuation due to toxicity was lower with axitinib (4%) than sorafenib (8%).
- Common adverse events included hypertension and fatigue with axitinib, and palmar-plantar erythrodysaesthesia with sorafenib.
Conclusions:
- Axitinib offers significantly longer PFS than sorafenib in the second-line treatment of advanced RCC.
- Axitinib represents a viable and effective treatment option for patients with advanced renal cell carcinoma.
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