Axitinib for kidney cancer: hint of considerable added benefit

The drug axitinib (trade name Inlyta®) has been approved since September 2012 for the treatment of people with advanced kidney cancer (advanced renal cell carcinoma) in whom previous treatment with sunitinib or a cytokine was unsuccessful. The German Institute for Quality and Efficiency in Health Care (IQWiG) has examined the added benefit of the drug pursuant to the "Act on the Reform of the Market for Medicinal Products" (AMNOG). IQWiG found a hint of a considerable added benefit over the drug sorafenib, because the risk of certain side effects is lower with axitinib. In contrast, an added benefit in comparison with everolimus is not proven, because of the lack of suitable data.

Axitinib compared with everolimus or sorafenib

When the Federal Joint Committee (G-BA) specified the appropriate comparator therapy (ACT), it distinguished between two treatment situations: in the case of ineffective previous treatment with sunitinib, axitinib was to be compared with everolimus. Had the patients previously received a cytokine, a comparison of axitinib with sorafenib was to be undertaken. This specification corresponds to the current approval status of everolimus and sorafenib.

Added benefit in comparison with everolimus is not proven

In its dossier, the drug manufacturer did not present any data suitable for the comparison with everolimus, i.e. for the patients previously treated with sunitinib. An added benefit of axitinib for this treatment situation is therefore not proven.

No relevant differences in important outcome criteria

A single approval study (AXIS study) was available to IQWiG for the comparison with sorafenib, i.e. for patients in whom previous treatment with a cytokine had been ineffective (cytokine population).

In terms of the outcomes "overall survival”, "symptoms” and "health-related quality of life”, there were no statistically significant differences in the treatment results of this study between the axitinib and the sorafenib group. This means that in respect of these outcome criteria, axitinib has neither advantages nor disadvantages.

Both positive as well as negative effects of axitinib

On the other hand, relevant differences were found for side effects (adverse events), where the risk with axitinib was sometimes greater, sometimes smaller than with sorafenib. For example, hair loss (alopecia), skin rash and the hand-foot syndrome occurred less often when axitinib was taken. In contrast, disturbances of the voice (dysphonia) were less common in patients who took sorafenib.

Results for side effects are susceptible to bias

However, these results are subject to several uncertainties. For instance, it is unclear which side effects occurred most often in the patients previously treated with a cytokine and how intense they were (severity). Therefore IQWiG rated both the negative and the positive effects not as an indication, but as a hint of a respectively lesser or added benefit of axitinib. The extent of both effects for patients can be considerable.

Overall, there is a hint of a considerable added benefit of axitinib in comparison with sorafenib in patients with advanced metastatic renal cell carcinoma, in whom previous treatment with a cytokine has failed.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on axitinib.

The G-BA website contains both general English-language information on benefit assessments pursuant to §35a Social Code Book V and specific German-language information on the assessment of axitinib.