EORTC-NCI-AACR: Avastin and Tarceva a Possible Bonus for Kidney Cancer Surgery

PRAGUE, Nov. 9 -- For metastatic kidney cancer, neoadjuvant targeted therapy is apparently safe and may prolong progression-free survival, researchers said here.

Eight weeks of induction therapy with Avastin (bevacizumab) and Tarceva (erlotinib) before cytoreductive surgery had some peri-operative complications, but few that could be pinned to the treatment, according to Eric Jonasch, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues.

Also progression-free survival among evaluable patients was 16.6 months, longer than expected for a "relatively challenging" group, Dr. Jonasch told a symposium on molecular targets and cancer therapeutics, organized by the European Organisation for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research.

But Dr. Jonasch cautioned in an interview that the finding is preliminary and the translational phase II study -- involving only 35 patients so far of a planned 50 -- is intended as "hypothesis-generating, not hypothesis confirming."

Dr. Jonasch and colleagues are enrolling previously untreated patients, without brain metastases, who have a performance status of 0 or 1 and predominant clear cell histology, and have not undergone cytoreductive nephrectomy.

Patients get intravenous Avastin, at 10 mg/kg, once every two weeks over the eight-week induction period, and 150 mg of Tarceva daily.

Dr. Jonasch reported here on 33 patients who can be evaluated for toxicity and 25 who can be evaluated for efficacy.

The drug therapy appeared to be safe, although there were some cases of what Dr. Jonasch called "superficial wound dehiscence" after surgery that is probably attributable to the medications. Also, one patient suffered a post-operative blood clot, and another developed a deep wound infection - both known adverse effects of the surgery.

In terms of efficacy, he said:

• Three patients had a partial response, including one who had a complete response of the primary tumor and stable disease in the metastatic lesion.
• 18 had stable disease, defined as less than a 30% shrinkage of the tumor.
• Four had progressive disease.

Dr. Jonasch cautioned that the induction period is short and that "you could see stability in as many patients without treatment."

One goal of the study, he said, was to see if Avastin had an effect on its target, the vascular endothelial growth factor (VEGF) receptor, in renal cell carcinoma. In fact, although patients appeared to respond to treatment, Dr. Jonasch said, the VEGF receptor did not appear to be down-regulated in the tumor tissue.

"It's an important lesson to us that things are not always as simple as they seem," he said. One implication, he said, is that even though all the patients' tumors looked the same under the microscope, they may differ in the cellular signaling pathways that are active.

"We are probably dealing with a much more heterogenous tumor from the standpoint of what's going in within the cell," he said.

It's that sort of insight that makes the study valuable, commented Alexander Eggermont, M.D., Ph.D., of Erasmus Medical Center in Rotterdam, The Netherlands.

Dr. Eggermont, the symposium's chairman, said in an interview, it's "a very useful development in clinical research to neoadjuvant therapy in the four weeks prior to surgery to find out something that gives you direct information about whatever agent you are using."

But, he added, it's too early to suggest that the drug combination might be used clinically to decrease the size of tumors. "At this point, you can't make any claim of treatment efficacy or that it would play a convincing role in making non-resectable tumors resectable," Dr. Eggermont said.