Abstract P4-21-04: Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent/metastatic breast cancer (PERUSE)
Authors: Bachelot T , Puglisi F , Ciruelos E , Peretz-Yablonski T , Schneeweiss A , Easton V , Lindegger N , Restuccia E , Miles D 
Published: March 2017

Abstract
Background: First-line (1L) docetaxel+trastuzumab+pertuzumab (THP) for HER2-positive metastatic breast cancer (MBC) significantly improved progression-free survival (PFS) and overall survival in the phase III CLEOPATRA trial, and led to the approval of this regimen. PERUSE (NCT01572038) was designed to assess the safety and efficacy of investigator's choice of taxane+HP for 1L locally recurrent (LR)/MBC, and allows exploration of safety and efficacy in a larger population.
Methods:
PERUSE is a multicenter, single-arm phase IIIb study. Patients (pts) with Eastern Cooperative Oncology Group performance status ≤2 and no prior systemic therapy for LR/MBC (except endocrine therapy) receive T, paclitaxel (PAC), or nab-PAC plus H (8 mg/kg→6 mg/kg every 3 weeks [q3w]) and P (840 mg→420 mg q3w) until disease progression (PD) or unacceptable toxicity. The primary endpoint is safety. Secondary endpoints include best overall response (BOR) and PFS.
Results:
The safety/ITT population includes 1436 pts at data cutoff (1 Apr 2016). Median follow-up was 17.2 mo (range, &lt;1–41.4). The median pt age was 54 years (range 23–87), 64% had hormone receptor-positive disease, 27% received adjuvant H, and 75% had visceral disease. Pts received T, PAC, nab-PAC, H, and P for a median of 3.8 mo (range &lt;1–24.2; n=791), 4.2 mo (&lt;1–36.6; n=618), 3.9 mo (&lt;1–17.3; n=73), 16.0 mo (&lt;1–45.9; n=1435), and 16.1 mo (&lt;1–45.9; n=1436), respectively.
Most pts discontinued taxanes for 'other' reasons (25%), adverse events (AEs; 16%), PD, or investigator decision (15% each); H, for PD or AEs (46% and 7%); and P, for PD or AEs (46% and 8%).
Grade ≥3 treatment-emergent AEs (TEAEs) of interest are shown in table 1. Serious TEAEs were reported in 282 (36%) pts on T, 185 (31%) on PAC, and 21 (32%) on nab-PAC. Preliminary efficacy by taxane is shown in table 2.
Table 1Pts, n (%)TPACNab-PAC n=775n=589n=65Neutropenia110 (14)31 (5)1 (2)Diarrhea62 (8)50 (8)4 (6)Febrile neutropenia81 (10)7 (1)0Fatigue21 (3)10 (2)1 (2)Asthenia16 (2)10 (2)0Peripheral neuropathy10 (1)15 (3)0Anemia11 (1)12 (2)2 (3)Left ventricular dysfunction1 (&lt;1)9 (2)1 (2)
Table 2 TPACNab-PACBOR, based on pts with measureable disease at baseline, n (%)n=659n=482n=53Complete72 (11)80 (17)4 (8)Partial442 (67)319 (66)38 (72)Stable disease112 (17)62 (13)8 (15)PD18 (3)12 (2)2 (4)Missing15 (2)9 (2)1 (2)PFS, ITT populationn=775n=589n=65Pts with events, n (%)439 (57)324 (55)40 (62)Median, mo (95% confidence interval)19.6 (17.4–22.6)24.8 (20.7–27.0)18.1 (11.9–34.2)25th–75th percentile, mo9.4–not reached (NR)10.2–NR7.9–NR
Conclusion:
The preliminary findings of this large, single-arm study suggest that safety and efficacy of 1L taxane+HP for HER2-positive LR/MBC are in keeping with the results of the phase III CLEOPATRA study. There was less febrile neutropenia with PAC/nab-PAC+HP compared with THP, and preliminary PFS was similar to that seen in the CLEOPATRA study for all taxane+HP combinations.
Citation Format: Bachelot T, Puglisi F, Ciruelos E, Peretz-Yablonski T, Schneeweiss A, Easton V, Lindegger N, Restuccia E, Miles D. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent/metastatic breast cancer (PERUSE) [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 P4-21-04.