TY - JOUR
T1 - Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer
T2 - A multicenter phase 2 study
AU - Meulendijks, Didier
AU - De Groot, Jan Willem B
AU - Los, Maartje
AU - Boers, James E.
AU - Beerepoot, Laurens V.
AU - Polee, Marco B.
AU - Beeker, Aart
AU - Portielje, Johanna E A
AU - Goey, Swan H.
AU - De Jong, Robert S.
AU - Vanhoutvin, Steven A L W
AU - Kuiper, Maria
AU - Sikorska, Karolina
AU - Pluim, Dick
AU - Beijnen, Jos H.
AU - Schellens, Jan H M
AU - Grootscholten, Cecile
AU - Tesselaar, Margot E T
AU - Cats, Annemieke
PY - 2016/5/1
Y1 - 2016/5/1
N2 - BACKGROUND The current study was a multicenter, single-arm, phase 2 study performed to investigate the feasibility and efficacy of bevacizumab combined with docetaxel, oxaliplatin, and capecitabine (B-DOC) in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, previously untreated, gastric or gastroesophageal adenocarcinoma. METHODS Tumor HER2 status was determined centrally. Patients received 6 cycles of bevacizumab at a dose of 7.5 mg/kg, docetaxel at a dose of 50 mg/m2, and oxaliplatin at a dose of 100 mg/m2 (all on day 1) combined with capecitabine at a dose of 850 mg/m2 twice daily (days 1-14) every 3 weeks followed by maintenance with capecitabine and bevacizumab in patients with disease control. The primary objective was to demonstrate a progression-free survival (PFS) of >6.5 months, according to the 95% confidence interval (95% CI). Secondary endpoints included safety, objective response rate, overall survival (OS), analyses of circulating tumor cells (CTCs), and pharmacogenetic analyses. RESULTS Sixty eligible patients were enrolled. The median PFS was 8.3 months (95% CI, 7.2-10.9 months). The objective response rate was 70% (95% CI, 55%-83%) and the disease control rate was 96% (95% CI, 85%-99%). The median OS was 12.0 months (95% CI, 10.2-16.1 months). According to CTC-AE v4.0, the most common treatment-related grade ≥3 adverse events were neutropenia (20%), leukocytopenia (18%), diarrhea (15%), and nausea/vomiting (15%). The presence of CTCs at baseline was strongly predictive of PFS (hazard ratio [HR], 3.8; P =.007) and OS (HR, 3.4; P =.014). The methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype was strongly associated with PFS (HR, 4.7 for TT vs CC or CT; P =.0007) and OS (HR, 5.9; P =.0001). CONCLUSIONS The B-DOC regimen plus maintenance was feasible and active. CTCs were found to be prognostic in patients treated with B-DOC. Docetaxel-based triplet chemotherapy as a backbone for targeted therapies is feasible and deserves further study.
AB - BACKGROUND The current study was a multicenter, single-arm, phase 2 study performed to investigate the feasibility and efficacy of bevacizumab combined with docetaxel, oxaliplatin, and capecitabine (B-DOC) in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, previously untreated, gastric or gastroesophageal adenocarcinoma. METHODS Tumor HER2 status was determined centrally. Patients received 6 cycles of bevacizumab at a dose of 7.5 mg/kg, docetaxel at a dose of 50 mg/m2, and oxaliplatin at a dose of 100 mg/m2 (all on day 1) combined with capecitabine at a dose of 850 mg/m2 twice daily (days 1-14) every 3 weeks followed by maintenance with capecitabine and bevacizumab in patients with disease control. The primary objective was to demonstrate a progression-free survival (PFS) of >6.5 months, according to the 95% confidence interval (95% CI). Secondary endpoints included safety, objective response rate, overall survival (OS), analyses of circulating tumor cells (CTCs), and pharmacogenetic analyses. RESULTS Sixty eligible patients were enrolled. The median PFS was 8.3 months (95% CI, 7.2-10.9 months). The objective response rate was 70% (95% CI, 55%-83%) and the disease control rate was 96% (95% CI, 85%-99%). The median OS was 12.0 months (95% CI, 10.2-16.1 months). According to CTC-AE v4.0, the most common treatment-related grade ≥3 adverse events were neutropenia (20%), leukocytopenia (18%), diarrhea (15%), and nausea/vomiting (15%). The presence of CTCs at baseline was strongly predictive of PFS (hazard ratio [HR], 3.8; P =.007) and OS (HR, 3.4; P =.014). The methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype was strongly associated with PFS (HR, 4.7 for TT vs CC or CT; P =.0007) and OS (HR, 5.9; P =.0001). CONCLUSIONS The B-DOC regimen plus maintenance was feasible and active. CTCs were found to be prognostic in patients treated with B-DOC. Docetaxel-based triplet chemotherapy as a backbone for targeted therapies is feasible and deserves further study.
KW - bevacizumab
KW - capecitabine
KW - clinical trial
KW - docetaxel
KW - gastric cancer
KW - phase 2
UR - http://www.scopus.com/inward/record.url?scp=84960426049&partnerID=8YFLogxK
U2 - 10.1002/cncr.29864
DO - 10.1002/cncr.29864
M3 - Article
AN - SCOPUS:84960426049
SN - 0008-543X
VL - 122
SP - 1434
EP - 1443
JO - Cancer
JF - Cancer
IS - 9
ER -