54
TDM-1 2.4 mg/m^2 was selected by the independent data moni-
toring committee after stage one of the study and further com-
parison was performed against weekly paclitaxel. After a median
follow-up of 17.5 months, the median overall survival was
7.9 months with TDM-1 and 8.6 months with paclitaxel (HR
1.15, 95% CI 0.87–1.51; p = 0.86). Although superiority of
TDM-1 was not demonstrated, it has a better safety profile. The
value of transtuzumab is being investigated in adjuvant setting.
The TOXAG study is an open-label single arm study that evalu-
ates the addition of trastuzumab to adjuvant chemoradiotherapy
with oxaliplatin and capecitabine (NCT01748773).The results of clinical trials on the addition of anti-EGFR mono-
clonal antibody, cetuximab and panitumumab, have been disap-
pointing in two global phase III randomized studies. Patients in
the EXPAND study were randomized to cetuximab with cisplatin
and capecitabine or chemotherapy alone [ 19 ]. Worse overall sur-
vival (9.4 months vs 10.7 months, HR 1.00; p = 0.95) and pro-
gression-free survival (4.4 months vs 5.6 months, HR 1.09;
p = 0.32) were seen with the addition of cetuximab. More skin
reaction was also observed with cetuximab. The REAL-3 study
mirrored the negative findings of the EXPAND study. Patients had
a significantly shorter overall survival (8.8 months vs 11.3 months,
HR 1.37; p = 0.013) if they received panitumumab and EOC (epi-
rubicin, oxaliplatin, and capecitabine) [ 20 ]. Again, significantly
increased frequency of anti-EGFR monoclonal antibody-related
toxicities including diarrhea, rash, mucositis, and hypomagnesemia
were seen with panitumumab. The third anti-EGFR monoclonal
antibody nimotuzumab is being investigated in a phase III study
with irinotecan in the second-line setting (NCT01813253). While
the result of nimotuzumab is awaited, anti-EGFR monoclonal
antibodies should not be used in routine clinical practice.Aberrant angiogenesis is the hallmarks of cancer and vascular endo-
thelial growth factor (VEGF) is a key mediator of angiogenesis in
normal and tumor tissue [ 21 ]. Bevacizumab is the first anti- VEGF
monoclonal antibody to be approved for anti-cancer treatment,
and it was the first anti-angiogenic agent to be evaluated in gastric
and esophagogastric adenocarcinoma. AVAGAST was a multi-
center phase III study that randomized patients to cisplatin and
capecitabine with or without bevacizumab [ 22 ]. The study failed
to meet its primary end point in improving overall survival
(10.1 months to 12.1 months, HR 0.87; p = 0.1002) but both the
progression-free survival (6.7 months vs 5.3 months, HR 0.80;
p = 0.0037) and response rate (46% vs 37.4%, p = 0.0315) were
significantly improved. Pre-planned subgroup analyses suggested
regional differences in the efficacy: patients enrolled in North1.1.2 Epidermal Growth
Factor Receptor
1.2 Vascular
Endothelial Growth
Factor (VEGF)
Ka-On Lam and Dora L. W. Kwong