Abstract P4-21-02: Pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: Efficacy analysis of a phase II cardiac safety study (TRYPHAENA)
Authors: Schneeweiss A , Chia S , Hickish T , Harvey V , Eniu A , Waldron-Lynch M , Eng-Wong J , Kirk S , Cortés J 
Published: May 2019

Abstract
Background:
The multicenter, open-label Phase II TRYPHAENA study (NCT00976989) showed that neoadjuvant pertuzumab (P) + trastuzumab (H) + chemotherapy (anthracycline-containing or anthracycline-free) was generally well tolerated with low rates of symptomatic left ventricular systolic dysfunction (LVSD, the primary endpoint), in patients (pts) with HER2-positive, operable, locally advanced or inflammatory breast cancer. All three arms were highly clinically active: total pathologic complete response in the breast and axilla (tpCR; ypT0/is, ypN0) rates were 55–64%. We now report long-term disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cardiac safety.
Methods:
Pts were randomized 1:1:1 to six 3-weekly neoadjuvant treatment cycles. Arm A: H + P (cycles 1–6) + fluorouracil, epirubicin, cyclophosphamide (FEC, cycles 1–3) + docetaxel (T) (cycles 4–6), Arm B: FEC (cycles 1–3) followed by T + H + P (cycles 4–6), Arm C: T + H + P + carboplatin (cycles 1–6). Adjuvant H was then given to complete 1 year of treatment. Doses: P 840mg loading and 420mg maintenance; H 8mg/kg loading and 6mg/kg maintenance; T 75mg/m2, up to 100mg/m2 if tolerated (Arms A and B); fluorouracil 500mg/m2; epirubicin 100mg/m2; cyclophosphamide 600mg/m2; carboplatin area under the plasma concentration–time curve 6. A preplanned descriptive analysis of DFS (time from surgery until disease progression or death), PFS (time from randomization until disease progression or death, equivalent to the common definition of event-free survival), and OS (time from randomization until death from any cause) was conducted 5 years after randomization of the last pt.
Results:
Median follow-up was balanced across arms (61.1 months in Arm A; 61.8 months in Arm B; 60.9 months in Arm C); 3-year Kaplan–Meier (KM) survival estimates and 95% CIs are shown in the table.
Arm A n=73Arm B n=75Arm C n=773-year KM survival estimate, %DFS87 (79–95)88 (80–96)90 (82–97) PFS89 (81–96)89 (81–96)87 (80–95) OS94 (89–100)94 (89–100)93 (87–99)
For all three arms combined, the hazard ratio for DFS in pts who achieved tpCR versus those who did not achieve tpCR was 0.27 (95% CI 0.11–0.64). During post-treatment follow-up, 2/72 (2.8%) pts in Arm A, 3/75 (4.0%) in Arm B, and 4/76 (5.3%) in Arm C had LVSD (any grade). Of the pts with LVSD, only 1 pt experienced an event indicative of symptomatic LVSD (assessed as NYHA class II and grade ≥3). Also during this period, 8 pts in Arm A (11.1%), 12 (16.0%) in Arm B, and 9 (11.8%) in Arm C experienced LVEF declines to &lt;50% and ≥10% from baseline.
Conclusions:
The 3-year DFS and PFS rates were similar between treatment arms and were comparable to rates previously observed in the neoadjuvant NeoSphere study. Pts who achieved tpCR had improved DFS compared with those who did not achieve tpCR, supporting previous findings of an association between pCR and long-term outcomes (Cortazar et al, Lancet 2014). The combination of P, H, and standard anthracycline-containing or anthracycline-free chemotherapy regimens was generally well tolerated and no new safety signals were identified with 5 years follow-up.
Citation Format: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: Efficacy analysis of a phase II cardiac safety study (TRYPHAENA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-02.