Abstract P5-20-04: Safety of adjuvant treatment with pertuzumab plus trastuzumab after neoadjuvant anthracycline-based chemotherapy in patients with HER2-positive localized breast cancer: Updated results from the BERENICE study
Authors: Dang C , Ewer MS , Delaloge S , Ferrero J-M , Verrill M , Colomer R , Vieira C , de la Cruz Merino L , Lucas J , Werner TL , Douthwaite H , Bradley D , Waldron-Lynch M , Eng-Wong J , Swain SM 
Published: February 2018

Background Anti-HER2 therapies are associated with a risk of cardiac toxicity, particularly as part of anthracycline-based regimens. BERENICE (NCT02132949), a nonrandomized, Phase 2 cardiac safety study showed neoadjuvant treatment with pertuzumab (P) + trastuzumab (H) and 2 common anthracycline–taxane-based regimens had a safety profile consistent with prior studies of P+H, and was associated with high pathologic complete response rates. Here we report safety data from the P+H adjuvant treatment period (AP).

Methods Patients (pts) with centrally confirmed, localized HER2-positive breast cancer and normal cardiac function received 4 q2w dose-dense doxorubicin and cyclophosphamide cycles (60/600mg/m2) then 12 qw paclitaxel injections (80mg/m2; Cohort A), or 4 q3w fluorouracil/epirubicin/cyclophosphamide cycles (500/100/600 mg/m2) then 4 q3w docetaxel cycles (75mg/m2, up to 100mg/m2;Cohort B). In both cohorts, 4 q3w cycles of P (loading:840mg; maintenance:420mg) + H (loading:8mg/kg; maintenance:6mg/kg) were started with taxane therapy and continued in the adjuvant setting (for up to 13 cycles to complete 1 year of treatment). Surgery was scheduled after 8 cycles of preoperative therapy. Primary endpoints were incidence of New York Heart Association (NYHA) Class III/IV heart failure and incidence of left ventricular ejection fraction (LVEF) declines (≥10%-points from baseline to &lt;50%; asymptomatic and symptomatic events) assessed by ECHO/MUGA. Confirmed LVEF declines were defined as significant LVEF declines at 2 consecutive visits.

Results In total, 397 pts received ≥1 dose of study medication and were included in the overall treatment period (OTP) safety analysis. Of these, 371 (Cohort A:181; Cohort B:190) pts entered the AP and were included in the AP safety analysis. Mean (SD) number of AP treatment cycles of P and H were 12.3 (2.0) in Cohort A and 12.3 (2.2) in Cohort B. In the AP, incidence of heart failure was minimal (0.5%) and confirmed LVEF decline incidence was low (Table 1).

Table 1: Cardiac AE Cohort ACohort B OTP n=199AP n=181OTP n=198OTP n=190NYHA Class III/IV heart failure    Events, n4011Pts with event, n (%)3(1.5)01(0.5)1(0.5)LVEF decline    Events, n36223429Pts with LVEF decline, n (%)21(10.6)14(7.7)22(11.1)20(10.5)Pts with confirmed LVEF decline, n (%)7(3.5)5(2.8)7(3.5)6(3.2)

General adverse events (AEs) are shown in Table 2; 26 (14.4%) pts in Cohort A and 45 (23.7%) in Cohort B had diarrhea AEs (mostly grade 1).

Table 2: General AE Cohort ACohort BPts, n (%)OTP n=199AP n=181OTP n=198AP n=190Any AE198(99.5)171(94.5)198(100.0)171(90.0)Grade ≥3 AE109(54.8)23(12.7)126(63.6)40(21.1)Serious AE54(27.1)15(8.3)61(30.8)17(8.9)AE leading to P or H discontinuation19(9.5)9(5.0)14(7.1)11(5.8)

Conclusion P+H in the adjuvant setting, following P+H with anthracycline-based regimens in the neoadjuvant setting, are associated with low incidence of cardiac AEs. Cardiac safety results for P+H in the AP and OTP of BERENICE were consistent with results from prior studies evaluating adjuvant treatment with single-agent H, suggesting the addition of P to H in the adjuvant setting does not increase cardiac toxicity.

Citation Format: Dang C, Ewer MS, Delaloge S, Ferrero J-M, Verrill M, Colomer R, Vieira C, de la Cruz Merino L, Lucas J, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Eng-Wong J, Swain SM. Safety of adjuvant treatment with pertuzumab plus trastuzumab after neoadjuvant anthracycline-based chemotherapy in patients with HER2-positive localized breast cancer: Updated results from the BERENICE study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-04.