Everolimus monotherapy is usually well tolerated with promising activity in patients with previously treated metastatic gastric cancer, Japanese investigators announced.

Everolimus, an orally bioavailable inhibitor of mammalian target of rapamycin, has shown anticancer activity in preclinical cellular and animal models and in patients with advanced gastric cancer.

"Given the poor long-term outcomes associated with surgical and traditional chemotherapeutic management of advanced gastric cancer, it is important to examine the use of new targeted agents in this population," Hiroya Takiuchi, MD, with Osaka Medical College, pointed out.

Takiuchi reported findings in 53 patients with metastatic gastric adenocarcinoma who received daily everolimus after failing up to two prior chemotherapy regimens.

"Gastric cancer is the fourth most common cancer worldwide and the second most common cause of cancer mortality, with an estimated 700,000 deaths annually," Takiuchi observed.

"While surgical resection for gastric cancer is curative, patients commonly present with unresectable disease," he added. "What's more, the relapse rate following curative-intent resection is high [roughly 60%]."

Various combination chemotherapy regimens are used for treating advanced gastric cancer, with a median overall survival typically less than 1 year, he said.

In the present phase 2 trial, oral everolimus, 10 mg/day, was administered in continuous 28-day cycles until the patient developed progressive disease or unacceptable toxicity or chose to quit the study prematurely for any other reason, with a dose reduction allowed for tolerability.

The primary study end point was disease control rate (DCR), which referred to the percentage of patients with a complete response, partial response, or stable disease as the best overall response.

Trial participants had a median age of 63 years, and most were men.

The study population was evenly split between second-line and third-line patients. Most patients had been pretreated with 5-fluorouracil alone or with cisplatin, and about half had undergone a prior gastrectomy.

The study showed a DCR of 56%, a rate that occurred in both secondand third-line patients. Although no complete or partial responses were documented, 45% of patients had a decrease in tumor size from baseline by independent radiologic review. The median overall survival was 10.1 months, with a median follow-up time of 9.6 months.

Adverse events were typically grade 1 or 2 in severity. Grade 3 adverse events occurred in 20 patients, and grade 4 adverse events that were considered to be possibly due to everolimus treatment occurred in only four patients.

Takiuchi said that, based on these favorable results, a phase 3 trial is currently under way that is comparing everolimus plus best supportive care with placebo plus best supportive care in patients with advanced gastric cancer whose disease has progressed after prior systemic chemotherapy.