ASCO: Neuroendocrine Tumors Respond to Treatment with RAD001

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CHICAGO -- The investigational drug RAD001 has demonstrated activity in the treatment of neuroendocrine tumors, researchers reported here.

CHICAGO, June 7 -- Carcinoid tumors and pancreatic islet cell lesions appear to be sensitive to treatment with the investigational drug RAD001 (everolimus), researchers said here.

In a phase II trial, James Yao, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston said that 72% of patients achieved stable disease and 20% of patients treated with RAD001achieved a partial response. Dr. Yao

"We still have no effective treatment for these neuroendocrine cancers," said Dr. Yao said at the American Society of Clinical Oncology meeting. "Yet the diagnoses of these tumors are on the rise."

The investigators tested RAD001 -- an mTOR (mammalian target of rapamycin) inhibitor -- in both a 5-mg and 10-mg dose. Patients were also treated with depot octreotide (Sandostatin), to help manage complications of the disease, although it has not shown any evidence of being able to control growth of tumors.

In the study, researchers enrolled 60 patients -- 30 patients on each dose of the drug. Half the patients had islet cell tumors and half had carcinoid tumors. Among the findings:

  • Median progression-free survival (for both doses) was 59 weeks.
  • Twenty-seven percent of patients treated with 10 mg of RAD001 achieve a partial response and 70% had stable disease, with a median progression-free survival of 62 weeks. At the 5-mg dose the partial response rate was 13%, and 73% had stable disease, with a median progression-free survival of 50 weeks.
  • Among patients with carcinoid tumors, the partial response rate was 13% versus a partial response rate of 27% among patients with islet cell tumors.
  • At 64 weeks, the progression-free survival was longer from patients with carcinoid tumors than for patients with islet cell tumors, at 50 weeks.

Not surprisingly, patients who entered the study with progressive disease fared worse than those who had stable disease at baseline, Dr. Yao said.

The patients who were progressing at the start achieved a 50-week progression-free survival while those who were stable at the beginning of the study achieved a 73-week progression free survival (P=0.01)

"Anti-tumor activity assessed by RECIST (Response Evaluation Criteria in Solid Tumors) response and progression-free survival was promising for both patients with carcinoid and pancreatic neuroendocrine tumors," Dr. Yao said.

He noted that additional phase II and phase III trials with the drug are under way.

Gary Schwartz, M.D., of Memorial Sloan-Kettering Cancer Center in New York, who discussed Dr. Yao's presentation, said that while the work with RAD001 was promising, the drug is not ready yet for prime time.

Dr. Schwartz suggested it is possible that some of the actions of RAD001 may enhance tumor growth and sandostatin's molecular actions may mute those effects.

"We need to wait for the outcome of on-going clinical trials comparing sandostatin alone to sandostatin plus RAD001," he said.