Pixantron (1) – Pixuvri®

• Clinical trials
  • The PIX301 trial is cited in the pharmaceutical manufacturer’s dossier to demonstrate additional benefit. This is a randomised controlled trial in which Pixantron monotherapy was compared with a monotherapy determined individually for each patient by the doctor, using one of seven antineoplastic drugs specified in the protocol.

Patient-specific therapy as determined by the treating doctor, in particular therapy containing bleomycin, cyclophosphamide, etoposide, ifosfamide, methotrexate, mitoxantrone, rituximab, trofosfamide, vinblastine, vincristine or vindesine, provided that, taking prior treatment into account, the active ingredients (INN) are once again suitable for treatment, and subject to the respective German marketing authorisation status and approved dosages

• Compared with the appropriate comparator therapy determined by the G-BA, on which this assessment is based, the comparator therapy used in the PIX301 study exhibits limitations relevant to the decision.
• The appropriate comparator therapy determined by the G-BA is patient-specific therapy as determined by the treating doctor, with particular consideration to be given to those antineoplastic active ingredients (INN) that have marketing authorisation for the relevant therapeutic indication. Both monotherapy and combination therapy are eligible for consideration.
• By contrast, in the control group of the PIX301 study, treatment was determined on an individual patient basis at the doctor’s discretion; however, according to the study protocol, the doctor’s choice was restricted to seven INN active ingredients, which, moreover, were to be used exclusively as monotherapy.
• In the G-BA’s view, the restriction to monotherapy alone is open to question, given that, according to the current state of medical knowledge, there is no standard treatment for the therapeutic situation in question and that combination therapy may also be an option on a case-by-case basis.
• Furthermore, some of the active ingredients used are explicitly authorised only for combination therapy. Overall, of the seven active ingredients used in the study’s control group, only two have marketing authorisation in Germany for the use as practised in the study.
• The pre-treatment of patients in the PIX301 study does not correspond to the standard of care and treatment in Germany.
• In the study, only 55 per cent of all enrolled patients had been pre-treated with rituximab, whereas in Germany, treatment with rituximab is standard practice in first-line therapy.
• This is also reflected in the study’s patient data, according to which 91 per cent of Western European and US patients had been pre-treated with rituximab. By contrast, only 37 per cent of patients from other regions – who made up the majority of the PIX301 study population – had received prior treatment with rituximab.
• This difference is significant, as prior treatment or lack thereof with rituximab is relevant to the outcome of subsequent therapies.
• A further imbalance is evident in the proportion of patients who had previously undergone a stem cell transplant: 37 per cent of patients from Western Europe and the US compared with 8 per cent of patients from other regions.
• Overall, the PIX301 study does not reflect the appropriate comparator therapy or the standard of care in Germany with regard to prior treatments.
• The results of the study therefore do not allow a conclusion to be drawn regarding the additional benefit of Pixantron.
• An additional benefit over the appropriate comparator therapy is not proven.

Courtesy translation only, please refer to the German original.