Liposomal doxorubicin in combination with bortezomib for relapsed or refractory multiple myeloma.
OBJECTIVE
On May 17, 2007, doxorubicin HCl liposome injection (Doxil) in combination with bortezomib (Velcade) received approval from the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma after at least one prior therapy that has not included bortezomib. Liposomal doxorubicin's efficacy and safety were demonstrated in a phase III, randomized, multicenter, international trial comparing the combination of this agent plus bortezomib vs bortezomib alone in multiple myeloma patients who had not previously received bortezomib and had received at least one prior therapy. Here we summarize the FDA review of the data that support this approval.


RESULTS
An interim analysis of time to disease progression (TTP), the primary endpoint, was conducted after 249 TTP events in this study that randomized 324 patients to liposomal doxorubicin plus bortezomib treatment and 322 patients to bortezomib monotherapy. Time to progression was significantly prolonged in the combination arm (median TTP = 9.3 months) compared with bortezomib monotherapy (median TTP = 6.5 months), P < .0001 (log-rank test); hazard ratio = 0.55 (95% confidence interval = 0.43-0.71). The response rates were similar between the two arms and not statistically different; however, among responding patients, the median duration of response was longer with the combination--10.2 months compared to 7.0 months in the monotherapy arm. Adverse reactions occurred more frequently with the combination therapy. As compared to the monotherapy, frequent grade 3/4 adverse reactions with the combination were neutropenia and thrombocytopenia.


CONCLUSIONS
Liposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.
Ning
Yang-Min
YM
Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration Silver Spring, Maryland 20993-0004, USA. ningy@cder.fda.gov
He
Kun
K
Dagher
Ramzi
R
Sridhara
Rajeshwari
R
Farrell
Ann T
AT
Justice
Robert
R
Pazdur
Richard
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D017277:Drug Approval; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D014481:United States
D000903:Antibiotics, Antineoplastic; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D004317:Doxorubicin