GAITHERSBURG, Md--Members of the FDA's Oncology Drug Advisory Committee (ODAC) agreed that Immu-nex Corp.'s Novantrone (mitoxan-trone)--in combination with corticosteroids--offers a clinical benefit to patients with hormone-resistant prostate cancer.
GAITHERSBURG, Md--Members of the FDA's Oncology Drug AdvisoryCommittee (ODAC) agreed that Immu-nex Corp.'s Novantrone (mitoxan-trone)--incombination with corticosteroids--offers a clinical benefit topatients with hormone-resistant prostate cancer.
However, the panel recommended further evaluation of trial databefore the FDA makes a decision. Novantrone was originally approvedin 1987 for use in acute myelogenous leukemia.
"Until recently, we have had no effective chemotherapy foradvanced prostate cancer," said Ian Tannock, MD, professorof medicine at the University of Toronto, who led the pivotalstudy of the drug. "Pain is the dominant problem."
At the meeting, the company presented data from two unblindedclinical trials to back up its contention that the drug combinationdecreases pain, suppresses prostate cancer, and significantlyimproves quality of life in advanced disease patients.
The pivotal study of the drug's analgesic effects involved 161patients treated at 11 centers with Novantrone plus pred-nisoneor prednisone alone. Its primary endpoint called for a reductionof two points on a six-point pain scale with stable analgesicuse.
Of 80 patients receiving the combination, 21 (26%) achieved thisendpoint, as did 10 (12%) of the 81 patients given prednisoneonly. Those getting the drug combination had a median time toprogression of 168 days, compared with 62 days in the prednisone-onlygroup. PSA was reduced in 27% of patients who received the combination,compared with 5% of patients in the prednisone-only group. Therewas no significant difference in median survival (339 vs 324 days).
A supportive study involved 119 prostate cancer patients givenNovantrone plus hydrocortisone and 123 given hydrocortisone aloneat 62 centers. This study did not examine the primary endpointof the first study, but did find a PSA decrease in 14% of patientsand a time to progression of 218 days in the Novantrone-hydrocortisonegroup versus a PSA drop in 5% of patients and a progression timeof 122 days for those getting hydrocortisone only.
The FDA's assessment of the studies disagreed little with Immunex'sinterpretation of the data, Julie Beitz, MD, said. "The painrelief, supported by the length of time to progression, resultsin net clinical benefit to the patients," she said.
Some panel members expressed concern about whether the evidencefor Novantrone was clear enough to warrant approval, given theunblinded nature of both studies, the differences in the two studyprotocols, and the possibility of serious flaws in the pivotalstudy and the incomplete reporting of the supportive study. However,members also pointed out that the pivotal study has been publishedin a peer-reviewed journal (J Clin Oncology 15:1756-1764, 1996).
The panel agreed 9-to-0 that the two-point improvement in painfound in the pivotal study was clinically meaningful. However,they voted unanimously that the second study did not support thepivotal study. On the question of whether Novantrone plus corticosteroidsoffer a net benefit to hormone-resistant prostate cancer patients,the panel agreed 6-to-2, with one abstention. Nonetheless, thepanel asked the FDA and Immunex to do further analyses to clarifythe meaning of the data in both studies.