ODAC Recommends Approval of Verluma for Staging of SCLC

BETHESDA, Md--The Oncologic Drugs Advisory Committee (ODAC), ina vote of 9 to 4, recommended that Verluma imaging be approvedfor the initial staging of patients with biopsy-confirmed small-celllung cancer (SCLC). Verluma is a murine monoclonal antibody (MoAb)Fab fragment, targeted to the NR-LU-10 antigen and linked to technetium-99m.

Dr. Darrell Salk, of the University of Washington, Seattle, presentedinformation on Verluma on behalf of the sponsoring company, NeoRxCorporation (Seattle). Dr. Salk emphasized that Verluma is intendedonly for cancer staging and should not be used for the differentialdiagnosis of suspected lung tumors or metastatic disease.

Verluma whole body gamma camera imaging (see figure at right)is performed on an outpatient basis and has an outstanding historyof safety in studies of more than 500 patients, Dr. Salk said.It results in only a 6% rate of low-level HAMA (human antimouseantibody) responses, with no associated toxicity.

Most of the radioactive antibody from the test goes to the kidneys,where it is excreted. The rest goes to the tumor and remains concentratedthere. The radioactive antibody will also show up in the bonemarrow if cancer cells have traveled into the blood, he said

When Verluma imaging shows extensive cancer, no further testingis needed prior to the initiation of palliative treatment. Whenlimited disease is revealed, then additional diagnostic testsshould be performed.

In the pivotal phase III study conducted from July 1988 to July1989 at 24 US sites, a single dose was used, and imaging tookplace 14 to 17 hours after injection, Dr. Salk said.

The Verluma imaging process correctly staged 73 of 89 newly diagnosedSCLCs (82% accuracy), compared with 71% accuracy for CT of theabdomen, 63% for bone scan, 54% for bone marrow aspiration, 49%for CT of the head, and 44% for physical examination.

Verluma imaging alone identified 77% of patients who had extensivedisease, with a positive predictive value of 94%. There was a3% rate of false positives (cancer overstaged) and a 15% rateof false negatives (cancer understaged).

Dr. Andrew Turrissi, of the University of South Carolina, alsospeaking on behalf of Verluma imaging, said that the new procedureshould lead to more efficient, less expensive staging since, inthe case of extensive disease (approximately 70% of all SCLC patients),the full battery of tests need not be performed.

False-positive results can be eliminated with further clinicalinput, while false negatives show up with further testing, hesaid.

Dr. Salk added that the availability of a single test with theaccuracy of Verluma may also decrease the number of inaccuratestagings that stem from failure to perform one or more of thebattery of traditional tests.

Dr. George Mills, representing the Food and Drug Administration,said that "the odds were purposely stacked against Verlumain the phase III trial by blinding the Verluma tests but not blindingthe other tests. Even then, Verluma was far superior in accuracy."

He emphasized that since Verluma imaging is a biologic and a diagnosticprocedure, not a drug, the FDA does not require multiple clinicaltrials for its approval.