Managed Care - July 2008 - (Page H13) therapy is to extend a patient’s response to FIGURE 1 treatment for as long as possible. The most APEX response rates* important question with regard to maintenance therapy is whether continued use of 100 a novel agent previously used for induc90 tion is appropriate or whether this may re80 sult in more resistant relapses. P<.0001 Growing consensus exists that thalido70 mide may be the most appropriate agent for 60 use in the maintenance setting. However, 50 one study found that a longer event-free sur38% 40 vival (EFS) during the maintenance stage did not necessarily result in longer OS, as 30 25% PR 18% compared with other agents (Barlogie 2006). 20 One randomized trial did demonstrate 16% PR 7% nCR <1% nCR 10 that thalidomide is an effective maintenance <1% CR 6% CR 0 therapy in patients with myeloma (Attal Bortezomib Dexamethasone 2006). The study compared no maintenance *Median follow-up was 8.3 months. therapy (arm A), maintenance therapy with CR=complete response, nCR=near complete response, PR=partial response. pamidronate (Aredia) (arm B), and mainSource: Richardson 2005 tenance with pamidronate/thalidomide (arm C) in patients younger than age 65 (N=597) who were given high-dose induction therapy in 1 through 4, 9 through 12, and 17 through 20 for the form of a double ASCT two months earlier. Given as four 5-week cycles, followed by treatment on days adjunctive therapy, pamidronate is a second-generation 1 through 4, for five 4-week cycles. bisphosphonate, and a potent inhibitor of bone resorption. Although little benefit was seen among patients Compared with patients who received dexamethawho received pamidronate alone, improved EFS and OS sone, patients who received bortezomib had higher rerates were seen with the addition of thalidomide. Fiftysponse rates, significantly longer TTP (6.2 versus 3.5 five percent of patients in arm A, 57 percent in arm B, and months), and longer survival rates (Figure 1). 67 percent in arm C achieved CR or VGPR. The 4-year The 1-year survival rate was 80 percent among patients probability of survival was 77 percent in arm A, 74 pertaking bortezomib and 66 percent among patients taking cent in arm B, and 87 percent in arm C. Once investigadexamethasone (P=.003) (Richardson 2005). Because of tors determined that maintenance with thalidomide was the beneficial results with bortezomib, patients who were superior, the majority of patients crossed over to the assigned to receive dexamethasone were permitted to cross thalidomide arm and an overall survival benefit was over to receive bortezomib in a companion study. maintained for those who received thalidomide mainteSignificant primary toxicities associated with the use nance therapy upfront. It also was noted that mainteof bortezomib during the trial included thrombocytopenance treatment with pamidronate did not decrease the nia and peripheral neuropathy. A small number of paincidence of bone events. Ongoing clinical trials also are tients developed severe neuropathy (approximately 9 evaluating lenalidomide and bortezomib in this setting. percent), which was expected to be permanent in about half of this subgroup. Relapsed or refractory myeloma Lenalidomide trials. Two large phase 3 trials — one Several trials provide evidence for agents that may be based in North America (Weber 2007) and an internabeneficial for patients whose myeloma has relapsed or betional study (Dimopoulos 2007) demonstrated significome refractory despite prior therapies or transplants. cantly superior TTP in addition to exceptional overall reAPEX. In this trial, 669 patients who had received 1 to sponse rates and unprecedented rates of survival with 3 prior therapies were randomly assigned to receive either: lenalidomide plus dexamethasone, when compared with placebo plus dexamethasone (Figure 2, page 14). All patients — the majority of whom had relapsed • Intravenous bortezomib (1.3 mg/m 2 of bodyafter multiple prior therapies and transplantation —were surface area) on days 1, 4, 8, and 11, for eight 3-week randomized to receive lenalidomide 25 mg (days 1 cycles, followed by treatment on days 1, 8, 15, and through 21) with pulsed dexamethasone, or dexametha22, for three 5-week cycles, or sone alone. The overall response rates among patients • High-dose dexamethasone (40 mg orally) on days Response, % SUPPLEMENT / HEMATOLOGIC CANCER 13
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