Ramucirumab (trade name: Cyramza) is a monoclonal antibody, which blocks a receptor, reducing the growth of blood vessels and so reducing blood supply to the tumours. This aims to slow the growth of the tumours. As a so-called orphan drug, i.e. a drug for the treatment of rare diseases, ramucirumab was initially exempt from proof of an added benefit. With several expansions of the therapeutic indication, it has lost this special status.
Having already conducted early benefit assessments for two other oncological indications recently, the German Institute for Quality and Efficiency in Health Care (IQWiG) was now commissioned to investigate, based on a third manufacturer dossier, whether ramucirumab offers an added benefit in comparison with the appropriate comparator therapy for adults with advanced adenocarcinoma of the stomach or of the gastro-oesophageal junction. Since the requirements specified by the Federal Joint Committee (G-BA) for the appropriate comparator therapy and for the target population were not met in the studies cited by the drug manufacturer, such an added benefit is not proven.
Approved as combination and monotherapy
After previous chemotherapy, ramucirumab can be used either in combination with paclitaxel or alone if paclitaxel is inadequate for the patients. The G-BA specified different appropriate comparator therapies for both situations: in the first case, individually optimized treatment specified by the physician under consideration of the respective approvals, and in the second case, best supportive care (BSC).
Combination therapy: control arm did not concur with the G-BA’s specifications
For the first research question, the manufacturer cited the study RAINBOW, in which ramucirumab plus paclitaxel was compared with placebo plus paclitaxel. This study was unsuitable for conclusions on an added benefit of the combination therapy in comparison with the appropriate comparator therapy for several reasons. First, determining paclitaxel deviated from the specification of “individually optimized treatment specified by the physician”. …