Final-Phase Trial Underway for Everolimus in Gastric Cancer

March 18, 2010

Pretreated patients with metastatic gastric cancer experienced a boost in overall survival after treatment with everolimus (Afinitor), according to the results of a phase II trial presented at the 2010 Gastrointestinal Cancers Symposium.

ORLANDO—Pretreated patients with metastatic gastric cancer experienced a boost in overall survival after treatment with everolimus (Afinitor), according to the results of a phase II trial presented at the 2010 Gastrointestinal Cancers Symposium. Based on these favorable results, a randomized, phase III study of the drug has begun enrollment.

Fifty-four patients were enrolled in the trial, which was conducted at multiple Japanese institutions including the Osaka Medical College in Osaka, the National Cancer Center Hospital in Tokyo, and the Tochigi Cancer Center in Tochigi. The eligibility criteria were:

Histologically proven metastatic gastric cancer (MGC)
At least one measurable lesion per RECIST
At least one prior chemotherapy regimen with documented progressive disease
ECOG PS 0 or 1

Oral everolimus (10 mg) was administered daily. Results in 53 patients showed a disease control rate of 56%, a median progression- free survival of 2.7 months, and a median overall survival of 10.1 months. Grade 3 adverse events occurred in 20 patients and included anemia, fatigue, and stomatitis. Grade 4 adverse events, such as lymphopenia and hemorrhage, occurred in eight patients (abstract 52).

In another study presented at the GI Cancers Symposium, researchers from the Research Institute and Hospital at the National Cancer Center in Goyang, South Korea, found that S-1 plus irinotecan (Camptosar) and oxaliplatin (Eloxatin) (TIROX) induced marked tumor reduction in both primary and metastatic tumor sites in MGC. The toxicity profile with this treatment regimen was deemed tolerable.

For this phase II study, 44 patients with previously untreated MGC and measurable lesion, ECOG PS 0-2, and adequate organ function were eligible. Patients received S-1 (40 mg/m2 bid) on days one through 14; irinotecan (150 mg/m2) on day one, and oxaliplatin (85 mg/m2) on day one every three weeks. Treatment was continued in the absence of disease progression or unacceptable toxicity for a maximum of 12 cycles. A total of 393 cycles have been administered to date with a median of 11 cycles per patient.

Among 42 patients assessable for response, six patients had a complete response and 27 had a partial response for a 79% objective response rate.

At a median follow-up of 23.8 months, the median time-to-progression was 10.2 months; overall survival was 17.6 months. Grade 3/4 neutropenia developed in 66% of patients (abstract 78).