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Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma
Author(s) -
White Darrell,
Kassim Adetola,
Bhaskar Birbal,
Yi Jing,
Wamstad Karen,
Paton Virginia E.
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27745
Subject(s) - medicine , bortezomib , bevacizumab , multiple myeloma , clinical endpoint , hazard ratio , refractory (planetary science) , adverse effect , placebo , gastroenterology , proteasome inhibitor , phases of clinical research , progressive disease , oncology , surgery , randomized controlled trial , confidence interval , clinical trial , chemotherapy , pathology , physics , alternative medicine , astrobiology
BACKGROUND. Newer systemic therapies have significantly advanced the treatment of multiple myeloma, but additional agents are needed. Bortezomib is a proteasome inhibitor with efficacy in relapsed/refractory multiple myeloma that inhibits tumor angiogenesis, a process that has been implicated in multiple myeloma pathogenesis. METHODS. In AMBER(“A Randomized, Blinded, Placebo‐Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma”), patients with relapsed or refractory multiple myeloma were randomized to receive bortezomib (1.3 mg/m 2 on days 1, 4, 8, and 11 of each 21‐day cycle) and either placebo or bevacizumab (15 mg/kg on day 1 of each cycle) for up to 8 cycles. At completion, patients in the bortezomib‐plus‐bevacizumab arm could continue bevacizumab until they developed progressive disease or unacceptable toxicity. The primary endpoint was progression‐free survival (PFS). RESULTS. The stratified hazard ratio of PFS for the bevacizumab‐containing arm (n = 49) relative to the bortezomib monotherapy arm (n = 53) was 0.743 (95% confidence interval [CI], 0.43‐1.28; P = .2804); the median PFS was 6.2 months (95% CI, 4.4‐8.5 months) and 5.1 months (95% CI, 4.2‐7.2 months), respectively; the overall response rates were 51% and 43.4% ( P = .4029), respectively; and the median response duration was 6.9 months (95% CI, 4.73‐11.83 months) and 6.0 months (95% CI, 4.86‐8.31 months), respectively. Frequent adverse events occurred at similar rates across treatment arms, but hypertension, fatigue, and neuralgia occurred more frequently in the bevacizumab‐containing arm. CONCLUSIONS. The addition of bevacizumab to bortezomib in unselected patients with pretreated multiple myeloma did not result in significant improvements in efficacy outcomes. The combination was well tolerated, and no new safety concerns for either agent were identified. Cancer 2013. © 2012 American Cancer Society.