@article{ff8629a27b9f4367b7287e9d22a52d8c,
title = "Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication",
abstract = "Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.",
keywords = "HER2 positive, hormone receptor, metastatic breast cancer, overall survival, paclitaxel, pertuzumab",
author = "{PERUSE investigators} and D. Miles and E. Ciruelos and A. Schneeweiss and F. Puglisi and T. Peretz-Yablonski and M. Campone and I. Bondarenko and Z. Nowecki and H. Errihani and S. Paluch-Shimon and A. Wardley and Merot, {J. L.} and P. Trask and {du Toit}, Y. and C. Pena-Murillo and V. Revelant and D. Klingbiel and T. Bachelot and K. Bouzid and I. Desmoulins and B. Coudert and I. Glogowska and {Ciruelos Gil}, E. and F. Dalenc and F. Ricci and V. Dieras and B. Kaufman and A. Ferreira and M. Mano and H. Kalofonos and C. Andreetta and F. Montemurro and S. Barrett and Q. Zhang and D. Mavroudis and J. Matus and {Villarreal Garza}, C. and C. Beato and G. Ismael and X. Hu and {Abdel Azeem}, H. and R. Gaafar and C. Perrin and P. Kerbrat and J. Ettl and S. Paepke and E. Hitre and I. Lang and M. Trudeau and D. Geffen",
note = "Funding Information: We thank the patients, their families, the nurses and the investigators who participated in this study, members of the independent data monitoring committee, and Valerie Easton (former employee of F. Hoffmann-La Roche Ltd). Medical and operational management support was provided by IQVIA (formerly QuintilesIMS{\texttrademark}). Support for third-party medical writing assistance for this manuscript was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK), funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Funding Information: We thank the patients, their families, the nurses and the investigators who participated in this study, members of the independent data monitoring committee, and Valerie Easton (former employee of F. Hoffmann-La Roche Ltd). Medical and operational management support was provided by IQVIA (formerly QuintilesIMS{\texttrademark}). Support for third-party medical writing assistance for this manuscript was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK), funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. This work was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland (no grant number). DM has received honoraria for advisory boards from Roche/Genentech, Genomic Health and Eisai, and has been an invited speaker for Roche/Genentech and Genomic Health. EC has received consultancy fees from Roche, Lilly, Novartis and Pfizer, and has received honoraria for speaker engagements from Celgene, Roche, Novartis and Pfizer. AS has received honoraria for scientific talks from Roche, Celgene, AstraZeneca, Pfizer and Novartis, and travel support from Roche and Celgene. FP reports consultant/advisory roles for Amgen, AstraZeneca, Daichii-Sankyo, Eli Lilly, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer and Roche, and research funding from AstraZeneca, Eisai and Roche. TP-Y has received honoraria for advisory boards and lectures from F. Hoffmann-La Roche, Pfizer, Neopharm, MSD, AstraZeneca, Janssen, Teva, Screen Cell, Medison, AbbVie and Takeda, and has received travel support from F. Hoffmann-La Roche, Bristol-Myers Squibb, AstraZeneca and Janssen. MC reports participation in advisory boards for AstraZeneca, Novartis, AbbVie, Sanofi, Pfizer, Sandoz, ACCORD and Lilly GT1 group, consultancy roles for Pierre Fabre Oncology, Sanofi, Novartis, Servier and Sanofi, speaker bureau/expert testimony for Novartis and travel/accommodation/expenses from Pfizer, Novartis, Roche and AstraZeneca. IB and his institution have received an investigator fee from Roche for the PERUSE study. ZN has received travel/accommodation/expenses from Roche. HE reports advisory/consultancy roles for Roche, MSD, Pfizer, Astellas and Merck and speaker bureau/expert testimony for Novartis and Amgen. SP-S has received honoraria for consultancy and speaker engagements from Roche, Novartis, Pfizer, AstraZeneca, Nanostring and Teva. AW reports personal fees from Roche, NAPP, Amgen, MSD, Novartis, Pfizer, AstraZeneca, Pierre Fabre, ACCORD, Athenex, Gerson Lehmann Group, Coleman Expert Network Group and Guidepoint global; he also reports personal fees and other from Lilly and Daichii-Sankyo (all outside the submitted work) and employment with AstraZeneca after completion of this work. J-LM is employed by IQVIA, a clinical research organisation contracted by F. Hoffmann-La Roche. PT is an employee of Genentech and holds shares in F. Hoffmann-La Roche Ltd. YdT, CP-M, VR and DK are employees and shareholders of F. Hoffmann-La Roche Ltd. TB has received research funding from AstraZeneca, Novartis and Pfizer, and has acted as a consultant for and received travel grants from AstraZeneca, Roche, Novartis and Pfizer. Qualified researchers may request access to individual patient-level data through the clinical study data request platform ( https://vivli.org/). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here ( https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = oct,
day = "1",
doi = "10.1016/j.annonc.2021.06.024",
language = "English",
volume = "32",
pages = "1245--1255",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Elsevier Ltd.",
number = "10",
}