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Axitinib (Inlyta°): No better than sorafenib in kidney cancer

FEATURED REVIEW In patients with metastatic kidney cancer in whom interferon alfa has failed, the only available comparative trial showed that axitinib did not prolong overall survival compared to sorafenib. Axitinib has a burdensome adverse effect profile and carries a risk of numerous drug-drug interactions.
Full review (2 pages) available for download by subscribers.

Abstract

  • In patients with advanced-stage or metastatic kidney cancer, interferon alfa, a cytokine, prolongs survival by about 4 months, and sunitinib, a tyrosine kinase inhibitor, by about 9 months. When interferon alfa fails, sorafenib, another tyrosine kinase inhibitor, appears to prolong survival by an additional 3 months. There is currently no treatment that prolongs survival after failure of sunitinib.
     
  • Axitinib (Inlyta°, Pfizer), a new tyrosine kinase inhibitor, is authorised in the European Union for the treatment of patients with advanced kidney cancer in whom sunitinib or cytokine therapy has failed.
     
  • The only comparative trial was unblinded. It involved patients in whom a first line of treatment had failed. Axitinib did not prolong overall survival compared to sorafenib (median about 20 months). There was no difference between the groups, regardless of the first-line treatment.
     
  • The time to death or disease progression (based mainly on radiological criteria) was 2 months longer with axitinib (6.7 versus 4.7 months, a statistically significant difference), but only in patients who had previously been treated with a cytokine alone or with sunitinib. In addition, the assessors disagreed in 40% of cases, thus undermining the results.

  • Axitinib shares the adverse effect profile of tyrosine kinase inhibitors. Compared to sorafenib, it appears to cause less hair loss, skin disorders and bleeding, but more hypertension, thyroid disorders and venous thrombosis.
     
  • Axitinib is metabolised by several cytochrome P450 isoenzymes and inhibits
    P-glycoprotein, which creates a high potential for drug-drug interactions.
     
  • Axitinib is teratogenic in animals and should not be used during pregnancy.
     
  • In practice, the only trial results available in early 2013 suggest that, compared to sorafenib, axitinib does not prolong survival in patients with kidney cancer who have previously received interferon alfa. After sunitinib treatment failure, there is no evidence that axitinib is more clinically beneficial than appropriate supportive care. Its adverse effect profile is just as burdensome as that of sorafenib. It also carries a risk of numerous drug interactions.

©Prescrire 1 November 2013

"Axitinib. No better than sorafenib in kidney cancer" Prescrire Int 2013; 22 (143): 262-263. (Pdf, subscribers only)
Download the full review.
Pdf, subscribers only