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- Title
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: A multicenter phase 2 study.
- Authors
Meulendijks, Didier; de Groot, Jan Willem B.; Los, Maartje; Boers, James E.; Beerepoot, Laurens V.; Polee, Marco B.; Beeker, Aart; Portielje, Johanna E.A.; Goey, Swan H.; de Jong, Robert S.; Vanhoutvin, Steven A.L.W.; Kuiper, Maria; Sikorska, Karolina; Pluim, Dick; Beijnen, Jos H.; Schellens, Jan H.M.; Grootscholten, Cecile; Tesselaar, Margot E.T.; Cats, Annemieke
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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/m(2) , and oxaliplatin at a dose of 100 mg/m(2) (all on day 1) combined with capecitabine at a dose of 850 mg/m(2) 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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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. Cancer 2016;122:1434-1443. © 2016 American Cancer Society.
- Subjects
STOMACH cancer treatment; BEVACIZUMAB; DOCETAXEL; OXALIPLATIN; HER2 gene; EPIDERMAL growth factor receptors; COMBINATION drug therapy; THERAPEUTICS
- Publication
Cancer (0008543X), 2016, Vol 122, Issue 9, p1434
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.29864