Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab

SM Swain, A Schneeweiss, L Gianni, JJ Gao, A Stein, M Waldron-Lynch, S Heeson, MS Beattie, B Yoo, J Cortes, J Baselga

Research output: Contribution to journalArticle

Abstract

Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n=1443) had metastatic [CLEOPATRA (n=804)] or early-stage breast cancer [NeoSphere (n=416) and TRYPHAENA (n=223)] . The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥ 65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA). © The Author 2017.
Original languageEnglish
Pages (from-to)761-768
Number of pages8
JournalAnnals of Oncology
Volume28
Issue number4
DOIs
Publication statusPublished - 2017

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Diarrhea
Breast Neoplasms
Incidence
Febrile Neutropenia
Epidermal Growth Factor Receptor
human ERBB2 protein
pertuzumab
Comorbidity
Loperamide
Therapeutics
Pharmacology

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Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. / Swain, SM; Schneeweiss, A; Gianni, L; Gao, JJ; Stein, A; Waldron-Lynch, M; Heeson, S; Beattie, MS; Yoo, B; Cortes, J; Baselga, J.

In: Annals of Oncology, Vol. 28, No. 4, 2017, p. 761-768.

Research output: Contribution to journalArticle

Swain, SM, Schneeweiss, A, Gianni, L, Gao, JJ, Stein, A, Waldron-Lynch, M, Heeson, S, Beattie, MS, Yoo, B, Cortes, J & Baselga, J 2017, 'Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab', Annals of Oncology, vol. 28, no. 4, pp. 761-768. https://doi.org/10.1093/annonc/mdw695
Swain, SM ; Schneeweiss, A ; Gianni, L ; Gao, JJ ; Stein, A ; Waldron-Lynch, M ; Heeson, S ; Beattie, MS ; Yoo, B ; Cortes, J ; Baselga, J. / Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. In: Annals of Oncology. 2017 ; Vol. 28, No. 4. pp. 761-768.
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abstract = "Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n=1443) had metastatic [CLEOPATRA (n=804)] or early-stage breast cancer [NeoSphere (n=416) and TRYPHAENA (n=223)] . The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28{\%} to 72{\%} (grade 1, 21{\%}-54{\%}; grade 2, 8{\%}-37{\%}; grade 3, 0{\%}-12{\%}; grade 4, 0{\%}). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0{\%} to 8{\%}. Among pertuzumab-treated patients with diarrhea, 47{\%}-67{\%} received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0{\%} to 11{\%}. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥ 65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19{\%} versus 8{\%}). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74{\%} versus 63{\%}); the corresponding rates in the control arm were 53{\%} and 45{\%}, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA). {\circledC} The Author 2017.",
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T1 - Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab

AU - Swain, SM

AU - Schneeweiss, A

AU - Gianni, L

AU - Gao, JJ

AU - Stein, A

AU - Waldron-Lynch, M

AU - Heeson, S

AU - Beattie, MS

AU - Yoo, B

AU - Cortes, J

AU - Baselga, J

PY - 2017

Y1 - 2017

N2 - Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n=1443) had metastatic [CLEOPATRA (n=804)] or early-stage breast cancer [NeoSphere (n=416) and TRYPHAENA (n=223)] . The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥ 65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA). © The Author 2017.

AB - Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n=1443) had metastatic [CLEOPATRA (n=804)] or early-stage breast cancer [NeoSphere (n=416) and TRYPHAENA (n=223)] . The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥ 65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA). © The Author 2017.

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DO - 10.1093/annonc/mdw695

M3 - Article

VL - 28

SP - 761

EP - 768

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 4

ER -