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Clinical Trial
. 2021 Oct;32(10):1245-1255.
doi: 10.1016/j.annonc.2021.06.024. Epub 2021 Jul 2.

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

D Miles  1 , E Ciruelos  2 , A Schneeweiss  3 , F Puglisi  4 , T Peretz-Yablonski  5 , M Campone  6 , I Bondarenko  7 , Z Nowecki  8 , H Errihani  9 , S Paluch-Shimon  10 , A Wardley  11 , J-L Merot  12 , P Trask  13 , Y du Toit  14 , C Pena-Murillo  14 , V Revelant  15 , D Klingbiel  16 , T Bachelot  17 ; PERUSE investigators
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Free article
Clinical Trial

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

D Miles et al. Ann Oncol. 2021 Oct.
Free article

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.

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Conflict of interest statement

Disclosure 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.

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