ODAC Finds Study Data Inadequate to Recommend Evacet

SILVER SPRING, Md—The Food and Drug Administration’s 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, Liposome’s 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 3’s 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 Study 2.

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 Evacet’s efficacy in the first-line treatment of breast cancer. That left the pivotal study to support the sponsor’s claim, and many members questioned its adequacy. “In my heart, no pun intended, I believe the drug works, but I don’t think the data presented to date are adequate,” said David H. Johnson, MD, of Vanderbilt University Medical School.