Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

BACKGROUND: Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. OBJECTIVES: To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. METHODS: We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. RESULTS: Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. CONCLUSIONS: MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives.

Radiolabeled immunotherapy in non-Hodgkin's lymphoma treatment: the next step.

Radiolabeled immunotherapy (RIT) is becoming a significant step forward in the treatment management of non-Hodgkin's lymphoma (NHL). In this state-of-the-art review article, general details, practical and health economic aspects, and next steps of RIT in NHL are reviewed from the existing literature and latest abstracts. As 90Y-ibritumomab tiuxetan is the only marketed RIT in NHL in Europe, the special focus of this review is on 90Y-ibritumomab tiuxetan, although the whole spectrum of available RIT concepts is highlighted. There is strong evidence to suggest that RIT is not only a safe and efficacious add-on treatment option in third or second line to chemotherapy, but is also a convincing asset as first-line therapy in various indications of lymphoma.

Radionuclide therapy for hepatocellular carcinoma: indication, cost and efficacy.

A large number of patients with hepatocellular carcinoma (HCC) will have large and/or multiple inoperable tumours, precluding percutaneous ablation, such as percutaneous ethanol, acetic acid or hot saline injection, and radiofrequency ablation. Similarly, if the tumour is not accessible percutaneously or the tumour is subcapsular or subdiaphragmatic, percutaneous therapy is ruled out. Many patients will also have associated portal vein thrombosis, making them unsuitable for chemoembolisation, depending upon the level and severity of thrombosis. Such patients can be offered internal radioisotope therapy to prolong their survival and improve the quality of life. The aim of radioisotope therapy is to deliver the radioisotope to the hepatic tumour, where it must reside for a period sufficient to deliver the scheduled dose of radiation. At the same time the amount delivered to the normal liver parenchyma and other organs should be as low as possible. A variety of radioisotopes, such as lodine-131, Yttrium-90, Rhenium-188, Holmium-166 etc. can be used for this purpose and targeting of the therapeutic agent to the tumour may be achieved by 1) direct intra-tumour implantation of the radioisotope, 2) parenteral injection of radiolabelled antibodies specific to HCC antigens (radioimmunotherapy) or, 3) injecting the radioisotope through the hepatic artery directly into the tumour or trans-arterial radioisotope therapy (TART). The radioisotope therapy appears to be a very reasonable and effective therapeutic alternative, a) for the treatment of large inoperable HCC, particularly with portal vein thrombosis, b) treatment of small inoperable tumours unsuitable for percutaneous therapy because of any reason, c) as a neoadjuvant therapy before hepatic transplantation to reduce the risk of recurrence in the graft or before hepatic resection to shrink the tumour size, and d) as an adjuvant therapy, after surgery or percutaneous ablative therapy to reduce the risk of recurrence. Further, it can be very affordable if generator produced Re-188 is used, which appears to be equally or more effective and useful than other currently available radioisotopes. The availability of Re-188 in a generator form makes its storage, transportation, elution and usage very convenient and cost-effective, particularly at remote places and in developing countries. The use of generator also makes Re-188 available on a constant and need to need basis.

Molecular imaging and personalized medicine: an uncertain future.

The Food and Drug Administration has described their view of the role that imaging will play in the approval, and perhaps postapproval, use of new therapeutic drugs. The therapeutic drug industry and regulatory authorities have turned to imaging to help them achieve better efficiency and efficacy. We must extend this initiative by demonstrating that molecular imaging can also improve the efficiency and efficacy of routine treatment with these same drugs. The role of molecular imaging in personalized medicine, using targeted drugs in oncology, is very attractive because of the regional information that it provides (in many cases, with a functional or dynamic component), which cannot be provided by in vitro methods ("regional proteomics"). There is great potential for molecular imaging to play a major role in selecting appropriate patients and providing early proof of response, which is critical to addressing the conflict between the high price of treatment and limited reimbursement budgets. This is a new venture in both molecular imaging and targeted drugs. However, there are various regulatory, financial, and practical barriers that must be overcome to achieve this aim, in addition to the normal scientific challenges of drug discovery. There is an urgent need to reduce the cost (i.e., time and money) of developing imaging agents for routine clinical use. The mismatch between the current regulations and personalized medicine includes molecular imaging and requires the engagement of the regulatory authorities to correct. Therapeutic companies must be engaged early in the development of new targeted drugs and molecular imaging agents to improve the fit between the two drug types. Clinical trials must be performed to generate data that not only shows the efficacy of imaging plus therapy in a medical sense, but also in a financial sense. Molecular imaging must be accepted as not just good science but also as central to routine patient management in the personalized medicine of the future.

National cancer institute perspectives.

The National Cancer Institute (NCI) Perspectives this year presented information on the systemic targeted radionuclide therapy (STaRT) research projects: (1) being investigated at the NCI's Intramural Center for Cancer Research; (2) funded by NCI's Radiation Research Program and other extramural programs; and (3) the appropriate National Institutes of Health/NCI funding mechanisms applicable to researchers for obtaining funds for STaRT projects.

Radioimmunotherapy in non-Hodgkin lymphoma: opinions of nuclear medicine physicians and radiation oncologists.

UNLABELLED: Despite approval by the Food and Drug Administration and consistent reports of the efficacy and safety of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, these therapies are infrequently used. This study investigates the opinions and patterns of the use of radioimmunotherapy by nuclear physicians, affiliated researchers, nuclear medicine technologists, and radiation oncologists and aims to identify possible barriers to the use of this promising therapy. METHODS: An e-mail-based survey with 13 broad questions related to radioimmunotherapy was sent electronically to 13,221 Society of Nuclear Medicine members and radiation oncologists throughout the United States. RESULTS: Six hundred thirteen individuals (4.6%) responded to the electronic survey. Two hundred fifty-one responders (40.9%) had treated patients with non-Hodgkin lymphoma (NHL) with radioimmunotherapy in the last 24 mo. Of the responders, 29.5% used only (90)Y-ibritumomab tiuxetan, 7.6% used only (131)I-tositumomab, and 24.9% used both radiopharmaceuticals; 37.9% did not treat NHL with radioimmunotherapy. Most responders said their patients came from university hospitals (33.9%) or private offices (25.6%), and they mainly treated in a second-line (42.9%), third-line (35.6%), or consolidation (23.5%) setting. Major concerns were that referring oncologists and hematologists wanted to treat by themselves with nonradioactive compounds (mean ± SD, 3.418 ± 1.49) and that (90)Y-ibritumomab tiuxetan and (131)I-tositumomab were expensive (mean ± SD, 3.413 ± 1.35). Of the responders and involved physicians, 40.4% and 35.2%, respectively, did not know if their institution accepted Medicare patients for radioimmunotherapy. Almost 30% (29.6%) of the responders thought radioimmunotherapy would probably grow and 38.0% thought it would grow in importance in the future. Responders who did not administer radioimmunotherapy for NHL thought it took too much time to administer radioimmunotherapy (P < 0.01) and had concerns about the dosimetry procedure (P < 0.01) and radiation safety (P < 0.01). Individuals who perceived a negative future for radioimmunotherapy had significantly more concerns about the time-consuming administration process (P < 0.05) and the high cost of radioimmunotherapy (P < 0.05). Responders from academic centers had significantly fewer concerns about payment (P < 0.01), dosimetry (P < 0.01), and radiation safety (P < 0.01). CONCLUSION: Radioimmunotherapy was generally viewed positively by the surveyed population. However, limited referrals due to alternative nonradioactive therapies and logistic, educational, and economic concerns played an important role for subgroups in the perception of radioimmunotherapy for NHL.