with neoadjuvant-adjuvant trastuzumab, or neoadjuvant chemotherapy alone.
In study MO16432, trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance every 3 weeks) was administered concurrently with 10 cycles of neoadjuvant chemotherapy
as follows:
• Doxorubicin 60 mg/m2 and paclitaxel 150 mg/m2, administered 3-weekly for 3 cycles, which was followed by
• Paclitaxel 175 mg/m2 administered 3-weekly for 4 cycles,
which was followed by
• CMF on day 1 and 8 every 4 weeks for 3 cycles
which was followed after surgery by
• additional cycles of adjuvant trastuzumab (to complete 1 year of treatment)
The efficacy results from Study MO16432 are summarized in Table 12. The median duration of follow-up in the trastuzumab arm was 3.8 years.
Table 12 Efficacy results from MO16432
Parameter
Chemo + trastuzumab
(n=115)
Chemo only
(n=116)
Event-free survival
Hazard ratio
(95% CI)
No. patients with event
46
59
0.65 (0.44, 0.96)
p=0.0275
Total pathological complete response* (95% CI)
40%
(31.0, 49.6)
20.7%
(13.7, 29.2)
p=0.0014
Overall survival
Hazard ratio
(95% CI)
No. patients with event
22
33
0.59 (0.35, 1.02)
p=0.0555
* defined as absence of any invasive cancer both in the breast and axillary nodes
An absolute benefit of 13 percentage points in favour of the trastuzumab arm was estimated in terms of 3-year event-free survival rate (65% versus 52%).
astatic gastric cancer
Trastuzumab has been investigated in one randomised, open-label phase III trial ToGA (BO18255) in combination with chemotherapy versus chemotherapy alone.
Chemotherapy was administered as follows:
- capecitabine - 1000 mg/m2 orally twice daily for 14 days every 3 weeks for 6 cycles (evening of day 1 to morning of day 15 of each cycle)
or
- intravenous 5-fluorouracil - 800 mg/m2/day as a continuous intravenous infusion over 5 days, given every 3 weeks for 6 cycles (days 1 to 5 of each cycle)
Either of which was administered with:
- cisplatin - 80 mg/m2 every 3 weeks for 6 cycles on day 1 of each cycle.
The efficacy results from study BO18225 are summarized in Table 13:
Table 13 Efficacy results from BO18225
Parameter
FP
N=290
FP +H
N=294
HR (95% CI)
p-value
Overall survival, median months
11.1
13.8
0.74 (0.60-0.91)
0.0046
Progression-free survival, median months
5.5
6.7
0.71 (0.59-0.85)
0.0002
Time to disease progression, median months
5.6
7.1
0.70 (0.58-0.85)
0.0003
Overall response rate,%
34.5%
47.3%
1.70a (1.22, 2.38)
0.0017
Duration of response, median months
4.8
6.9
0.54 (0.40-0.73)
<0.0001
FP + H: fluoropyrimidine/cisplatin + trastuzumab
FP: fluoropyrimidine/cisplatin
a Odds ratio
Patients who were previously untreated for HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction not amenable to curative therapy were recruited to the trial. The primary endpoint was overall survival which was defined as the time from the date of randomization to the date of death from any cause. At the time of the analysis a total of 349 ran
