Phase II study of everolimus as a salvage treatment after failure of fluoropyrimidine and platinum in patients with metastatic gastric cancer positive for pS6Ser240/4expression

Abstract

Background: Everolimus is a macrolide derivative of rapamycin which inhibits mTOR. Our previous phase II study in 2nd line setting showed that everolimus had no significant activity with 1.7 months of median progression-free survival (PFS) in unselected population with gastric cancer (GC) and suggested that pS6Ser 240/4 might be a potential predictive biomarker of everolimus (Yoon et al, Br J Cancer. 2012;106:1039). In this study, we aimed to evaluate the efficacy and safety of everolimus in 2nd line GC patients selected by pS6Ser240/4 expression. Methods: The primary endpoint was 4-month PFS rate. Patients with metastatic or recurrent GC positive for pS6Ser240/4 were enrolled after failure of fluoropyrimidine and platinum. pS6Ser240/4positivity was defined as immunostain of 10% or more cancer cells with moderate or strong intensity. Patients received everolimus 10 mg p.o. once daily until disease progression or unacceptable toxicity. Results: Between December 2011 and May 2013, a total of 45 patients were enrolled. Median age was 58 years (range 34-78). Thirty-nine (86.7%) patients had ECOG performance status 0-1, and 6 (13.3%) had 2. In addition to fluoropyrimidine and platinum, 14 (31.1%) and 5 (11.1%) patients received docetaxel and irinotecan, respectively. One (2.2%) patient achieved a partial response and 26 (57.8%) showed stable disease. With a median follow-up of 13.3 months (range, 9.9-24.1) in surviving patients, the median PFS was 2.6 months (95% CI, 1.9-3.2), and 4-month PFS was 25.6%. The median overall survival was 5.8 months (95% CI, 5.1-6.6). Grade 3 or 4 drug-related toxicities in > 5% of patients included neutropenia (13.3%), anemia (13.3%), stomatitis (8.9%), and pneumonia (6.7%). Conclusions: Everolimus was safe, and it showed better activity in the current study which included biomarker-selected patients, compared with our previous study in biomarker-unselected population. Currently, further biomarker analysis is ongoing.