Pixantrone: no proof of added benefit

Pixantrone (trade name: Pixuvri) has been approved in Germany since May 2012 for the treatment of certain patients with aggressive B-cell non-Hodgkin's lymphoma (B-cell NHL). The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined the added benefit of the drug pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG). According to this, the manufacturer did not present any suitable data in its dossier, as it used results of a study where the patients in the control group were not treated in the way stipulated in the approval status of the appropriate comparator therapy specified by the Federal Joint Committee (G-BA). The manufacturer did not even provide an explanation why the data might still be applicable. Hence an added benefit of pixantrone cannot be derived from the dossier.

Comparison with individually tailored chemotherapy

Pixantrone, a drug from the group of cytostatics, is an option for adult patients who have experienced several cancer recurrences or who have already received 2 or 3 other (chemo) therapies without sufficient effect.

As appropriate comparator therapy, the G-BA specified a therapy individually tailored to the patient, for which, in principle, a wide variety of drugs are available. On the one hand, however, these drugs have to be an option for retreatment of the respective patient, and on the other, they have to be used according to their approval status.

Drugs in control arm are not approved as monotherapy

The manufacturer presented data from an approval study (PIX301) in its dossier. The manufacturer's analysis only used data of those patients for whom pixantrone is actually approved. But most patients in the comparator group did not receive approval-compliant treatment. They received etoposide or ifosfamide, two cytostatics, which in Germany are only approved in combination with other drugs in aggressive B-cell NHL, but which were used as mono-chemotherapy in the study.

Comparability of results not explained

In principle, studies where patients were treated outside the approval status might also be relevant for the assessment. But one condition has to be fulfilled: The effects of a treatment that does not comply with the approval status have to be sufficiently comparable to those of a treatment within the approval status. It has to be comprehensible why the therapy chosen instead is appropriate for the respective patients and at least not inferior to the appropriate comparator therapy specified by the G-BA. Because only then is it guaranteed that the treatment effect observed in the pixantrone group is at least not overestimated. However, the manufacturer did not provide a corresponding explanation in its dossier.

Hence, due to a lack of suitable data, an added benefit of pixantrone is not proven.

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.

An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on pixantrone.

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 pixantrone.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on www.informedhealthonline.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.