Abstract 288P
Background
P + H + docetaxel (DOC) is the standard first-line therapy for HER2-positive LR/mBC, based on results from the phase III CLEOPATRA trial. The single-arm PERUSE study (NCT01572038) assessed the safety and efficacy of P + H with investigator-selected taxane in this setting. Preliminary results by taxane have been reported [Bachelot, Ann Oncol 2019]; we present final safety and efficacy results.
Methods
Patients (pts) with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy [ET]) received DOC, paclitaxel (PAC) or nab-PAC with H (8→6 mg/kg q3w) + P (840→420 mg q3w) until disease progression or unacceptable toxicity. The primary endpoint was safety. Progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Subgroup analyses according to taxane and hormone receptor (HR) status were prespecified.
Results
1436 pts were treated (median age 54 y, 69% visceral disease, 55% prior (neo)adjuvant chemotherapy, 36% de novo mBC). At data cut-off (26 Aug 2019), median follow-up was 69 mo (range 0–87). Pts received a median of 16 mo of study treatment (24 cycles of P and H, 6 taxane cycles). The safety profile and efficacy results were consistent with CLEOPATRA. Grade ≥3 adverse events (AEs) occurred in 61% of pts (10% neutropenia, 8% diarrhoea) and were considered related to P in 20%, H in 17% and taxane in 36%. AEs led to discontinuation of P in 10% of pts, H in 9% and taxane in 20%. Median PFS was ∼21 mo, irrespective of HR status (table). 295 pts (21%) received maintenance ET. 679 pts (47%) received post-study anticancer therapy (monoclonal antibodies in 34%: 25% H, 19% T-DM1, 7% P). Table: 288P
| Subgroup | PFS | OS | ||
| Events (%) | Median (95% CI), mo | Events (%) | Median (95% CI), mo | |
| All (n=1436) | 872 (61) | 20.7 (18.9–23.1) | 658 (46) | 65.3 (60.9–70.9) |
| HR+ (n=918)a | 550 (60) | 20.6 (18.5–23.8) | 411 (45) | 66.7 (62.4–77.3) |
| HR– (n=512)a | 318 (62) | 20.7 (17.1–23.8) | 245 (48) | 60.2 (52.3–67.7) |
| DOC (n=775) | 479 (62) | 19.4 (16.9–22.1) | 351 (45) | 66.5 (61.7–77.3) |
| PAC (n=588) | 356 (61) | 23.2 (19.6–25.6) | 273 (46) | 64.0 (56.6–72.2) |
| Nab-PAC (n=65) | 35 (54) | 19.2 (11.7–37.1) | 28 (43) | 70.9 (39.7–NE) |
aHR status unknown in 6 pts. NE=not evaluable.
Conclusions
Final results from PERUSE are consistent with CLEOPATRA, support first-line P + H + taxane therapy for HER2-positive LR/mBC and suggest that PAC is a valid alternative to DOC as backbone chemotherapy.
Clinical trial identification
NCT01572038.
Editorial acknowledgement
Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche.
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
F. Hoffmann-La Roche.
Disclosure
D.W. Miles: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genomic Health. E.M. Ciruelos: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. A. Schneeweiss: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Molecular Partner. F. Puglisi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Research grant/Funding (self): Eisai; Research grant/Funding (self): AstraZeneca; Travel/Accommodation/Expenses: Celgene. T. Peretz-Yablonski: Advisory/Consultancy: Pfizer; Advisory/Consultancy: J&J; Advisory/Consultancy: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Medison; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: BMS. M. Campone: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Sandoz; Advisory/Consultancy: ACCORD; Advisory/Consultancy: Lilly; Advisory/Consultancy: GT1 group; Advisory/Consultancy: Pierre Fabre Oncology; Advisory/Consultancy: Servier; Travel/Accommodation/Expenses: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche. H. Errihani: Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Merck; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Amgen. S. Paluch-Shimon: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly. A.M. Wardley: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Athenex; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory/Consultancy: Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America; Advisory/Consultancy, Research grant/Funding (institution): Accord Research; Advisory/Consultancy: Coleman Research; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy: NAPP Pharma; Speaker Bureau/Expert testimony: Eisai; Leadership role, Full/Part-time employment, Medical Director: NIHR Manchester Clinical Research Facility at The Christie; Leadership role, Strategy Director: Association of Cancer Physicians; Leadership role, Committee Member: UK Breast Cancer Group; Leadership role, Committee Member: NHS England Chemotherapy Clinical Reference Group; Leadership role, Faculty: ESMO Breast cancer; Research grant/Funding (self): NIHR; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): 1G1 Therapeutics; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Spouse/Financial dependant: Andrew Wardley Limited; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Manchester Cancer Academy; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Outreach Research & Innovation Group Limited. J-L. Merot: Research grant/Funding (institution): Roche. Y. du Toit: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. D. Klingbiel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. V. Revelant: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. T. Bachelot: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Seattle Genetic. All other authors have declared no conflicts of interest.