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.

Abstract

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/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.

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. Cancer 2016;122:1434-1443. © 2016 American Cancer Society.

• Authors: Didier Meulendijks, Jan Willem B de Groot, Maartje Los, James E Boers, Laurens V Beerepoot, Marco B Polee, Aart Beeker, Johanna E A Portielje, Swan H Goey, Robert S de Jong, Steven A L W Vanhoutvin, Maria Kuiper, Karolina Sikorska, Dick Pluim, Jos H Beijnen, Jan H M Schellens, Cecile Grootscholten, Margot E T Tesselaar, Annemieke Cats
• Journal: Cancer (Cancer) Vol. 122 Issue 9 Pg. 1434-43 (05 01 2016) ISSN: 1097-0142 [Electronic] United States
• PMID: 26970343 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Taxoids
• Oxaliplatin
• Docetaxel
• Bevacizumab
• Capecitabine
• Methylenetetrahydrofolate Reductase (NADPH2)
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage)
• Capecitabine (administration & dosage)
• Docetaxel
• Drug Administration Schedule
• Female
• Humans
• Male
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Neoplastic Cells, Circulating
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Prospective Studies
• Receptor, ErbB-2
• Stomach Neoplasms (drug therapy, pathology)
• Taxoids (administration & dosage)