Endocrine Abstracts

Two anti-CD-20 radioantibody therapies: Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositutumomab (Bexxar) were approved in the USA in the early 2000s. The safety and efficacy of both Bexxar and Zevalin were proven relative to rituximab. While Zevalin remains on the market, sales are reportedly low. Bexxar exited the market in 2014 after low sales. Bexxar cost $26K USD, ‘very expensive’ by early 21st century standards, but low compared to cancer therapies in 2016. The challenges with Bexxar in the USA marketplace occurred at a time when private practice oncologists received the majority of their compensation from the mark up of drug prices between the wholesale and retail prices. Oncologists could prescribe rituximab at an infusion center, making money on every patient they treated. Prescribing radioimmunotherapy meant they would lose that revenue stream. In addition, there were logistical issues with radiopharmaceutical therapy, notably Bexxar, which had personalized dosimetry and challenges related to use I-131 as an inpatient in many locales. Other issues included US Medicare paying less than the cost of the dosimetric or therapeutic agent and a logistical arrangement which paid none of the providers much for their time. Both Bexxar and Zevalin have suffered from having multiple commerical owners of the key technology. Oncologists also had concerns of patients developing myelodysplastic syndromes, which could be fatal. In time, other therapies emerged, while the RIT were mainly static in their technologies such as Bendamustine and idelalisib.

A trial comparing 554 patients randomized to chemotherapy + rituximab or chemotherapy + Bexxar showed comparable outcomes. Bendamustine + ritiuximab appears to be even more effective. Zevalin remains available, as well as I-131 rituximab in Australia, but both are ‘underutilized’ relative to their efficacy. Lessons from these agents should serve to inform and caution the theranostics community. Theranostic agents need to ‘work’ in the disease and ‘work’ in the marketplace to succeed.