Secreted protein acidic and rich in cysteine (SPARC) reportedly influences the response to albumin-bound paclitaxel due to its characteristics of albumin-binding matrix-associated protein that may enhance the drug accumulation in the tumor tissue. However, its role in gastric cancer (GC) has been controversial. In this study, correlation between SPARC expression and the efficacy of nab-paclitaxel (nab-PTX) for GC was evaluated to explore its potential as a predictor of sensitivity.
In a multi-institutional prospective phase II trial (CCOG1303), efficacy of nab-PTX under a modified dose reduction criteria was evaluated in 47 advanced GC patients refractory to fluoropyrimidine. Correlation between SPARC expression on immunohistochemistry and efficacy endpoints was evaluated as a predetermined exploratory analysis in the CCOG1303 trial. SPARC staining was scored in two compartments: cancer associated fibroblasts (CAF) in the tumor stroma and tumor epithelial cells.
The SPARC expression in the tumor epithelia was higher than that in the non-tumorous epithelia in only 5 patients (11%), while negative or weaker SPARC staining in the tumor epithelia was observed in the remaining specimens. SPARC expression level in the CAF was classified into the following 3 categories: 1/3 or less (score 0), 1/3∼2/3 (score 1+), and 2/3 or more (score 2+) of CAF were positive for SPARC [18 patients (38%), 11 (23%), and 18 (38%), respectively]. There was no difference according to clinicopathological characteristics between CAF SPARC level [low (score 0) vs. high (score 1+/2+)]. CAF SPARC level (low vs. high) was not associated with the progression free survival (median, 4.8 vs. 3.0 months; P = 0.259), overall survival (median, 10.2 vs. 8.0 months; P = 0.419), time to treatment failure (median, 4.7 vs. 3.0 months; P = 0.291), and overall response rate (0 vs. 25%; P = 0.850).
SPARC level was not correlated with efficacy of nab-PTX for GC. The results of this exploratory analysis do not support the possibility of SPARC expression level for clinical biomarker regarding nab-PTX in GC.
Clinical trial identification
UMIN Clinical Trials Registry Registration Number: UMIN000012247
Legal entity responsible for the study
Chubu Clinical Oncology Group
Y. Kodera: Honoraria: Olympus, Chugai Pharma, Lilly, Johnson & Johnson, Ajinomoto, Takeda, Yakult Honsha, Taiho Pharmaceutical, Otsuka, Kaken Pharmaceutical, Ono Pharmaceutical, Asahi Kasei, Covidien/Medtronic All other authors have declared no conflicts of interest.