SILVER SPRING, MdThe Food and Drug Administrations
Oncologic Drugs Advisory Committee (ODAC) has voted 9 to 2 against
recommending approval of Evacet (doxorubicin HCl liposome injection,
The Liposome Company) for the first-line treatment of metastatic
breast cancer in combination with cyclophosphamide. The vote against
Evacet came after Liposome presented three controlled, randomized studies.
Study 1, Liposomes pivotal study, randomized 297 patients and
compared Evacet to conventional doxorubicin, evaluating each drug in
combination with cyclophosphamide. Study 2 randomized 224 patients to
compare the two drugs alone. The primary endpoints were time to
cardiotoxicity and tumor response rate.
Study 3 compared Evacet to epirubicin (Ellence), but it was
terminated early, the company said, for financial reasons. Because of
this termination, both the FDA reviewers and committee members
questioned the value of Study 3s findings.
The FDA analysis of study data put the median time to a cardiac event
at 15.2 months in the Evacet arm and 9.8 months in the conventional
doxorubicin group in Study 1, and 9.8 months vs 6.9 months,
respectively, in Study 2. The tumor response rate was 44% for Evacet
vs 43% for the doxorubicin arm in Study 1, and 26% in both groups in
ODAC members agreed unanimously that Studies 1 and 2 both showed that
Evacet is significantly less cardiotoxic than conventional
doxorubicin. However, they voted 10 to 0, with one abstention, that
Study 2 did not meet FDA standards as an adequate and
well-controlled clinical trial that demonstrated Evacets
efficacy in the first-line treatment of breast cancer. That left the
pivotal study to support the sponsors claim, and many members
questioned its adequacy. In my heart, no pun intended, I
believe the drug works, but I dont think the data presented to
date are adequate, said David H. Johnson, MD, of Vanderbilt
University Medical School.