Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

the SafeHer Study Group, Joseph Gligorov, B. Ataseven, Mark Verrill, Michele de Laurentiis, Kyung Hae Jung, H. A. Azim, N. Al-Sakaff, S. Lauer, M. Shing, Xavier Pivot, Dhurata Koroveshi, Kamel Bouzid, Monica Casalnuovo, Diana Cascallar, Ernesto Pablo Korbenfeld, Patricia Bastick, Jane Beith, Maree Colosimo, Michael Friedlander & 31 others Vinod Ganju, Michael Green, Kevin Patterson, Andrew Redfern, Gary Richardson, Timur Ceric, Kecman Gordana, Carlos Augusto Beato, Marcela Ferrari, Roberto Hegg, Vanessa Helena, Gustavo Fernando Ismael, Alvaro Edson Lessa, Max Mano, Alessandra Morelle, Jose Alberto Nogueira, Konstanta Timcheva, Antoaneta Tomova, Maya Tsakova, Ani Zlatareva-Petrova, Jamil Asselah, Hazem Assi, Christine Brezden-Masley, Stephen Chia, Ori Freedman, Mohammed Harb, Anil Abraham Joy, Swati Kulkarni, Catherine Prady, Alejandro Andres Acevedo Gaete, Luis Matamala

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Abstract

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

LanguageEnglish (US)
Pages237-246
Number of pages10
JournalEuropean Journal of Cancer
Volume82
DOIs
StatePublished - Sep 1 2017

Fingerprint

Breast Neoplasms
Safety
Drug Therapy
Therapeutics
human ERBB2 protein
Trastuzumab
Syringes
Population
Heart Failure
Hand
Research Personnel
Equipment and Supplies
Injections
Pharmaceutical Preparations

Keywords

  • Adjuvant
  • Breast cancer
  • HER2/neu
  • Herceptin
  • Subcutaneous
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{ffca877f16824e41853cd89f083c667b,
title = "Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients",
abstract = "Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin{\circledR} SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10{\%} of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7{\%}) experienced adverse events (AEs). Of the above, 128 (5.0{\%}) patients experienced AEs leading to study drug discontinuation; 596 (23.2{\%}) experienced grade ≥ 3 AEs and 326 (12.7{\%}) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9{\%}), including congestive heart failure in eight (0.3{\%}). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.",
keywords = "Adjuvant, Breast cancer, HER2/neu, Herceptin, Subcutaneous, Trastuzumab",
author = "{the SafeHer Study Group} and Joseph Gligorov and B. Ataseven and Mark Verrill and {de Laurentiis}, Michele and Jung, {Kyung Hae} and Azim, {H. A.} and N. Al-Sakaff and S. Lauer and M. Shing and Xavier Pivot and Dhurata Koroveshi and Kamel Bouzid and Monica Casalnuovo and Diana Cascallar and Korbenfeld, {Ernesto Pablo} and Patricia Bastick and Jane Beith and Maree Colosimo and Michael Friedlander and Vinod Ganju and Michael Green and Kevin Patterson and Andrew Redfern and Gary Richardson and Timur Ceric and Kecman Gordana and Beato, {Carlos Augusto} and Marcela Ferrari and Roberto Hegg and Vanessa Helena and Ismael, {Gustavo Fernando} and Lessa, {Alvaro Edson} and Max Mano and Alessandra Morelle and Nogueira, {Jose Alberto} and Konstanta Timcheva and Antoaneta Tomova and Maya Tsakova and Ani Zlatareva-Petrova and Jamil Asselah and Hazem Assi and Christine Brezden-Masley and Stephen Chia and Ori Freedman and Mohammed Harb and Joy, {Anil Abraham} and Swati Kulkarni and Catherine Prady and Gaete, {Alejandro Andres Acevedo} and Luis Matamala",
year = "2017",
month = "9",
day = "1",
doi = "10.1016/j.ejca.2017.05.010",
language = "English (US)",
volume = "82",
pages = "237--246",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer

T2 - European Journal of Cancer

AU - the SafeHer Study Group

AU - Gligorov, Joseph

AU - Ataseven, B.

AU - Verrill, Mark

AU - de Laurentiis, Michele

AU - Jung, Kyung Hae

AU - Azim, H. A.

AU - Al-Sakaff, N.

AU - Lauer, S.

AU - Shing, M.

AU - Pivot, Xavier

AU - Koroveshi, Dhurata

AU - Bouzid, Kamel

AU - Casalnuovo, Monica

AU - Cascallar, Diana

AU - Korbenfeld, Ernesto Pablo

AU - Bastick, Patricia

AU - Beith, Jane

AU - Colosimo, Maree

AU - Friedlander, Michael

AU - Ganju, Vinod

AU - Green, Michael

AU - Patterson, Kevin

AU - Redfern, Andrew

AU - Richardson, Gary

AU - Ceric, Timur

AU - Gordana, Kecman

AU - Beato, Carlos Augusto

AU - Ferrari, Marcela

AU - Hegg, Roberto

AU - Helena, Vanessa

AU - Ismael, Gustavo Fernando

AU - Lessa, Alvaro Edson

AU - Mano, Max

AU - Morelle, Alessandra

AU - Nogueira, Jose Alberto

AU - Timcheva, Konstanta

AU - Tomova, Antoaneta

AU - Tsakova, Maya

AU - Zlatareva-Petrova, Ani

AU - Asselah, Jamil

AU - Assi, Hazem

AU - Brezden-Masley, Christine

AU - Chia, Stephen

AU - Freedman, Ori

AU - Harb, Mohammed

AU - Joy, Anil Abraham

AU - Kulkarni, Swati

AU - Prady, Catherine

AU - Gaete, Alejandro Andres Acevedo

AU - Matamala, Luis

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

AB - Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

KW - Adjuvant

KW - Breast cancer

KW - HER2/neu

KW - Herceptin

KW - Subcutaneous

KW - Trastuzumab

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U2 - 10.1016/j.ejca.2017.05.010

DO - 10.1016/j.ejca.2017.05.010

M3 - Article

VL - 82

SP - 237

EP - 246

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

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