GRANITE-1: Second-line everolimus did not extend OS for advanced gastric cancer
2012 Gastrointestinal Cancers Symposium
SAN FRANCISCO — Patients assigned to everolimus monotherapy did not enjoy a survival benefit, according to phase-3 results from the GRANITE-1 trial presented here.
Although everolimus (Afinitor, Novartis) extended 6-month PFS, the drug failed to meet the primary endpoint of improved OS. Median OS was 5.39 months with everolimus vs. 4.34 months with placebo (HR=0.90; 95% CI, 0.75-1.08).
The difference was non-significant, said Eric Van Cutsem, MD, PhD, head of digestive oncology and professor of medicine with the University Hospital Gasthuisberg in Leuven, Belgium.
“There was no significant reduction in death in pre-treated patients with advanced gastric cancer exposed to everolimus,” he said. “The trial did not meet the primary endpoint. However, everolimus did reduce the risk for progression compared with best supportive care.”
Van Cutsem presented results from the international, double-blind, multi-center study at the 2012 ASCO Gastrointestinal Cancers Symposium.
The study enrolled 656 patients from 23 countries from July 2009 December 2010. Of them, 439 were randomly assigned to 10 mg daily everolimus and 217 were assigned to placebo. Both groups of patients received best supportive care. Researchers stratified randomization by region (Asia vs. rest of world) and previous lines of chemotherapy (1 vs. 2).
Roughly three-quarters of patients were men, 55.3% were from Asia, 47.7% received one previous line of chemotherapy and 50.6% had undergone gastrectomy.
Per local investigator assessment, median PFS was 1.68 months with everolimus compared with 1.41 months with placebo (HR=0.66; 95% CI, 0.56-0.78). Estimated 6-month PFS was 12.0% in the experimental group and 4.3% in the placebo group.
OS and PFS results were consistent across the various subgroups.
Patients assigned to everolimus demonstrated improved response. ORR was 4.5% (95% CI, 2.6%-7.1%) in the everolimus group compared with 2.1% (95% CI, 0.6%-5.3%) with placebo.
“What is going to be crucial, and what we hope to present at future meetings, is a biomarker analysis to identify the patients in whom we saw these minor responses and hints of activity,” Van Cutsem said.
Anemia was the most common grade-3/grade-4 adverse event (16.0% with everolimus vs. 12.6% with placebo), followed by anorexia and fatigue. The safety profile was consistent with previously results, Van Cutsem said. – by Jason Harris
Disclosure: Dr. Van Cutsem reports receiving research funding from Novartis.
This study suggests that everolimus has no meaningful activity as a single agent in patients with advanced gastric cancer. Given the observed improvement in PFS, everolimus may be interesting in combination with other biological or chemotherapy agents in future studies, especially if evaluated in first-line therapy. There have been very few documented responses in studies focusing on second and third line gastric cancer, making it very difficult to demonstrate a meaningful activity in this setting.
Tanios S. Bekaii-Saab, MD
HemOnc Today Editorial Board member
Disclosure: Dr. Bekaii-Saab reported no relevant financial disclosures.
For more information:
- Van Cutsem E. Abstract #LBA3. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2012; San Francisco.
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