Malattia HER-2 positiva Terapia adiuvante: quesiti irrisolti e nuovi studi U.O. di Oncologia Medica “Sandro Pitigliani” Dipartimento di Oncologia USL 4 Prato Angelo Di Leo

Index Trastuzumab in the adjuvant setting - state of the art - open questions

Open questions with trastuzumab in the adjuvant setting which chemotherapy regimen (i.e. with or without anthracyclines) sequentially after chemotherapy or concomitantly

My interpretation of BCIRG 006 data Trastuzumab = confirmed active treatment TCH as a possible alternative to AC → TH in patients with low-risk disease (T < 2 cm, N neg) No convincing evidence on the equivalence between TCH and AC → TH, particularly in moderate/high risk patients (unpowered study)

H=trastuzumab (4 mg/kg loading dose, followed by 2 mg/kg); A=doxorubicin dose 60 mg/m 2 ; C=cyclophosphamide, 600 mg/m 2 ; paclitaxel, 80 mg/m 2 ; q 3w=every 3 weeks; qw=weekly H qw x 52 H qw x 40 Schema: N9831 RT and/or hormonal therapy as indicated Paclitaxel qw x 12 Arm A:AC q 3w x 4 Paclitaxel qw x 12 Arm B:AC q 3w x 4 Paclitaxel qw x 12 + H qw x 12 Arm C: n=3,505 Perez EA N9831 RANDOMIZERANDOMIZE

Alive and disease free (%) N9831 Sequential (B) vs Concurrent (C) Disease Free Survival No. at risk 89.1% 85.7% 84.2% 79.8% Years from randomization AC → T → H (174 events) AC →T+H → H ( 138 events) Logrank p=

Conclusions DFS is significantly improved with the addition of 52 wks of trastuzumab to AC  T There is a statistically significant 33% reduction in the risk of an event with the sequential addition of trastuzumab following AC  T –5 yr DFS: 72% vs. 80% There is a strong trend for a 25% reduction in the risk of an event with starting trastuzumab concurrently with taxane relative to sequentially –5 yr DFS: 80% vs. 84% N9831

My personal view on treatment options High risk patient (N + and/or T ≥ 2cm) A-based Taxane + T T (1-yr. duration) Low risk patient (N - and T < 2cm) Taxane-based + T T (1-yr. duration) Topoisomerase II α gene status not ready for clinical practice Concomitant T + chemo > chemo T Short ( 1 yr.) T-based regimens still experimental