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
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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. / Miles, D; Ciruelos, E; Schneeweiss, A; Puglisi, F; Peretz-Yablonski, T; Campone, M; Bondarenko, I; Nowecki, Z; Errihani, H; Paluch-Shimon, S; Wardley, A; Merot, J-L; Trask, P; du Toit, Y; Pena-Murillo, C; Revelant, V; Klingbiel, D; Bachelot, T; PERUSE investigators.
In: ANN ONCOL, Vol. 32, No. 10, 10.2021, p. 1245-1255.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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
AU - Miles, D
AU - Ciruelos, E
AU - Schneeweiss, A
AU - Puglisi, F
AU - Peretz-Yablonski, T
AU - Campone, M
AU - Bondarenko, I
AU - Nowecki, Z
AU - Errihani, H
AU - Paluch-Shimon, S
AU - Wardley, A
AU - Merot, J-L
AU - Trask, P
AU - du Toit, Y
AU - Pena-Murillo, C
AU - Revelant, V
AU - Klingbiel, D
AU - Bachelot, T
AU - PERUSE investigators
AU - Muller , Volkmar
N1 - Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal, Humanized
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Breast Neoplasms/drug therapy
KW - Female
KW - Humans
KW - Neoplasm Recurrence, Local/drug therapy
KW - Receptor, ErbB-2/genetics
KW - Taxoids/therapeutic use
KW - Trastuzumab/adverse effects
KW - Treatment Outcome
U2 - 10.1016/j.annonc.2021.06.024
DO - 10.1016/j.annonc.2021.06.024
M3 - SCORING: Journal article
C2 - 34224826
VL - 32
SP - 1245
EP - 1255
JO - ANN ONCOL
JF - ANN ONCOL
SN - 0923-7534
IS - 10
ER -