1. CASI CLINICI: trattamento dei tumori HER2 positivi T1a,b N0 terapia sequenziale vs concomitante
Federico Piacentini MD Department of Oncology, Hematology and Respiratory Diseases
Modena University Hospital – Italy
Nonantola Novembre 2011

2. CLINICAL CASE - CASE HISTORY -
46-year old pre-menopausal woman
APRIL 1985: diagnosis of stage II Hodgkin Lymphoma, treated with MOPP x6 and mantle field RT
SEPTEMBER 2010: screen detected left breast carcinoma
conservative surgery and axillary node dissection
pT1b (0.6 cm) N0 (0/13), high grade, infiltrating ductal carcinoma
ER 95%, PgR 90%, MIB1 20% HER2 score 3+ by IHC, HER2 amplification by FISH: HER2/CEP17 >3
normal echocardiography with LVEF 60%
MOPP MECLORETAMINA-VINCRISTINA–PROCARBAZINA-PREDNISONE

3. Would you recommend adjuvant treatment(s) ?
- CLINICAL CASE -
pT1b N0, infiltrating ductal carcinoma
G3, ER 95%, PgR 90%, MIB1 20%, FISH positive
Would you recommend adjuvant treatment(s) ?
Yes No

4. Clinical outcome of pts
Clinical outcome of pts. with HER2+, T1a,bN0M0 BC treated w/o trastuzumab

5. Which regimen would you recommend?
- CLINICAL CASE -
pT1b N0, infiltrating ductal carcinoma
G3, ER 95%, PgR 90%, MIB1 20%, FISH positive
Which regimen would you recommend?
Chemotherapy plus trastuzumab - endocrine therapy at the end of chemoRx
Chemotherapy followed by endocrine therapy without trastuzumab
Endocrine therapy alone
Endocrine therapy (w/o chemoRx) + trastuzumab (off label)

7. Adjuvant trastuzumab trials: patient characteristics
Regimen N°
T ≤ 2 cm (%) N0
(%)
HR+
HERA
Observation
1698 43 33 50
H (1 year)
1703 39 32
Joint analysis
B31/N9831
AC  T
2017 40 15 52
AC  TH (1 year)
2028 38 14 51
BCIRG 006
AC  D
1073 41 29 54
AC  DH (1 year)
1074 28
DCcH (1 year)
1075
FinHER
DV  FEC
116 30 22 NR
DVH (9 weeks)  FEC 10
PACS-04
FEC or ED
268 49 - 61
FEC or ED  H (1 year)
260 58

8. DFS improvement in node-negative cohort of HERA trial
The node negative subgroup included 93 (8.5%) patients with tumor < 1cm in size
Untch M et al, Ann Oncol 2008; 19:

9. DFS in node-negative cohort of BCIRG 006 trial
T1a,b tumors eligible if N+ or N- with at least one of the following:
ER-/PgR-; G2-3; <35 years
DFS by tumor size in BCIRG 006 trial
p 0.03
p 0.09
Supplement to: Slamon et al., NEJM 2011; 365:

10. - CLINICAL CASE –
pre-treated for Hodgkin Lymphoma
pT1b N0, infiltrating ductal carcinoma
G3, ER 95%, PgR 90%, MIB1 20%, FISH positive
If you choose chemoRx + trastuzumab, which regimen would you recommend?
AC followed by taxane plus 1 yr trastuzumab
Non anthra-based regimen plus 1 yr trastuzumab
ChemoRx with short duration of trastuzumab (ShortHER trial)
Other

11. Which schedule of trastuzumab?
- CLINICAL CASE –
pre-treated for Hodgkin Lymphoma
pT1b N0, infiltrating ductal carcinoma
G3, ER 95%, PgR 90%, MIB1 20%, FISH positive
Which schedule of trastuzumab?
Trastuzumab administered sequentially for 1 year after the completion of chemotherapy
Trastuzumab started concomitantly with chemotherapy and administered up to 1 year

12. Sequential vs Concurrent trastuzumab
NCCTG N9831 trial
- Follow up mediano di 6 anni - When testing
- Whether DFS differed with respect to the timing of trastuzumab addition to AC then paclitaxel, the log-rank P value was .0216, which did not cross the prespecified O’Brien-Fleming boundary of significance (.00116) at this first interim analysis
Perez EA et al., JCO 2011

13. BCIRG 006
ADVERSE EVENTS
Slamon et al., NEJM 2011; 365:

14. adjuvant trastuzumab and cardiotoxicity
Trial
CHF NYHA 3-4 %
Syst. dysf. %
No trastuzumab
0-0.7 NR
BCIRG 006 DCH
0.4
HERA
0.6
1.4
N9831 armB (seq)
2.8
5.0
BCIRG 006 AC-DH
2.0
N9831 armC (comb)
3.3
6.6
NSABP B31
3.8
11.7

15. … OUR CHOICE … RT* OT** q 3w, for one year * IG-IMRT by Tomotherapy
Related citations
8. Image-guided intensity-modulated radiotherapy
RT*
OT**
Docetaxel + Carboplatin
Trastuzumab
* IG-IMRT by Tomotherapy
** LhRh-agonist plus Tamoxifen