ASCO: Anti-VEGF Agents Show Activity in Thyroid and Ovarian Cancer

CHICAGO, June 3 -- Two novel therapies targeting vascular endothelial growth factor (VEGF) demonstrated activity in refractory thyroid and ovarian cancer, investigators reported here.

Axitinib, an oral inhibitor of VEGF receptor 1, 2, and 3, led to partial responses in 30% of a group of patients with refractory thyroid cancer, reported Ezra Cohen, M.D., of the University of Chicago, at the American Society of Clinical Oncology meeting.

The antiangiogenic fusion protein VEGF-Trap led to stable disease or partial response after four weeks in 85% of a group of women with recurrent, heavily treated, platinum-resistant ovarian cancer, said William P. Tew, M.D., of Memorial Sloan-Kettering Cancer Center in New York, in another ASCO report. However, by week 30 only 4% of patients had at least stable disease.

Axitinib was evaluated in patients with advanced thyroid cancer, said Dr. Cohen. The malignancy often can be treated successfully with surgery and radiation. "But patients who fail standard therapy, unfortunately, have a five-year survival of 30%, with very few, or in some instances non-existent, treatment options," he added.

There have been no new drugs approved for thyroid cancer in over 30 years, noted Dr. Cohen.

The axitinib data emerged from a phase II, single-arm, multicenter study involving 60 patients with thyroid cancer refractory to conventional therapy. The patients received axitinib at 5 mg BID, and the primary endpoint was response rate, as defined by RECIST criteria.

Dr. Cohen reported that 18 patients (30%) responded to the treatment. An additional 25 (42%) had stable disease for at least 16 weeks, and 23 of the 25 had some degree of tumor shrinkage.

Response duration ranged between one and 16 months. The most common side effects were fatigue, diarrhea, and stomatitis-mucositis, and proteinuria, which occurred in 40% to 50% of patients, nausea (32%), and hypertension (28%). Grade 3-4 adverse events were uncommon.

Median progression-free survival was 18.6 months, and 37 (62%) of patients remain alive without evidence of progression. Dr. Cohen emphasized that the positive results occurred "in a disease setting where there are few treatment options."

The VEGF-Trap fusion protein (aflibercept) is being tested in an ongoing phase II trial involving patients with heavily pretreated, platinum-resistant ovarian cancer. The study has an accrual target of 200 patients, 153 of them evaluable for response, said Dr. Tew.

Patients are being randomized to 2 mg/kg or 4 mg/kg of VEGF-Trap, administered every two weeks. All patients have received at least three prior chemotherapy regimens. The patients' disease is resistant to topotecan (Hycamtin) or liposomal doxorubicin (Doxil), in addition to platinum.

So far, 13 patients (8%) have had radiologically confirmed partial responses. Additionally, 21 patients (13%) had at least a 50% decrease in levels of the tumor marker CA-125, and seven of 23 have had resolution of ascites. Four-week data showed that 138 (85%) patients had stable disease or partial responses, decreasing to 41% at 14 weeks, 15% and 22 weeks, and 4% at 30 weeks.

The most common side effects have been hypertension (46%), headache (39%), dysphonia (35%), fatigue (28%), nausea (21%), and asthenia (20%). Grade 3/4 toxicity has been uncommon, except for hypertension in 18% of patients.

"VEGF-Trap as a single intravenous agent has activity in patients with advanced chemotherapy-refractory ovarian cancer," Dr. Tew concluded. "VEGF-Trap has an acceptable safety profile, and accrual continues toward the goal of 200 patients."