rr;PH arm and 7.9 years (range: 0.0 to 12.2) for the AC→P arm; Median duration of long term follow-up for the BCIRG 006 study was 10.3 years in both the AC→D arm (range: 0.0 to 12.6) arm and the DCarbH arm (range: 0.0 to 13.1), and was 10.4 years (range: 0.0 to 12.7) in the AC→DH arm
Early breast cancer (neoadjuvant-adjuvant setting)
So far, no results are available which compare the efficacy of trastuzumab administered with chemotherapy in the adjuvant setting with that obtained in the neo-adjuvant/adjuvant setting.
In the neoadjuvant-adjuvant treatment setting, study MO16432, a multicentre randomised trial, was designed to investigate the clinical efficacy of concurrent administration of trastuzumab with neoadjuvant chemotherapy including both an anthracycline and a taxane, followed by adjuvant trastuzumab, up to a total treatment duration of 1 year. The study recruited patients with newly diagnosed locally advanced (Stage III) or inflammatory EBC. Patients with HER2+ tumours were randomised to receive either neoadjuvant chemotherapy concurrently 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 summarised 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
No. patients with event
46
59
Hazard Ratio
(95% CI)
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
No. patients with event
22
33
Hazard Ratio
(95% CI)
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%).
Metastatic 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 – 1,000 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 summarised 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
T |
