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
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 (...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 July 2021
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| In: |
Annals of oncology
Year: 2021, Volume: 32, Issue: 10, Pages: 1245-1255 |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2021.06.024 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.annonc.2021.06.024 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753421021050 
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| Author Notes: | D. Miles, E. Ciruelos, A. Schneeweiss, F. Puglisi, T. Peretz-Yablonski, M. Campone, I. Bondarenko, Z. Nowecki, H. Errihani, S. Paluch-Shimon, A. Wardley, J.-L. Merot, P. Trask, Y. du Toit, C. Pena-Murillo, V. Revelant, D. Klingbiel & T. Bachelot, on behalf of the PERUSE investigators |
| Summary: | 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. |
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| Item Description: | Collaborators: T. Bachelot, K. Bouzid, M. Campone, I. Desmoulins, B. Coudert, I. Bondarenko, Z. Nowecki, I. Glogowska, E. Ciruelos Gil, H. Errihani, F. Dalenc, F. Ricci, V. Dieras, B. Kaufman, S. Paluch-Shimon, A. Wardley, A. Schneeweiss und viele andere Gesehen am 29.01.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2021.06.024 |