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

J Gligorov, B Ataseven, M Verrill, M De Laurentiis, K H Jung, H A Azim, N Al-Sakaff, S Lauer, M Shing, X Pivot, SafeHer Study Group, Michele Aieta

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)237-246
Number of pages10
JournalEuropean Journal of Cancer
Volume82
DOIs
Publication statusPublished - Sep 2017

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

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Injections, Subcutaneous
  • Middle Aged
  • Receptor, ErbB-2
  • Survival Analysis
  • Trastuzumab
  • Young Adult
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study

Cite this

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. / Gligorov, J; Ataseven, B; Verrill, M; De Laurentiis, M; Jung, K H; Azim, H A; Al-Sakaff, N; Lauer, S; Shing, M; Pivot, X; SafeHer Study Group ; Aieta, Michele.

In: European Journal of Cancer, Vol. 82, 09.2017, p. 237-246.

Research output: Contribution to journalArticle

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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.",
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author = "J Gligorov and B Ataseven and M Verrill and {De Laurentiis}, M and Jung, {K H} and Azim, {H A} and N Al-Sakaff and S Lauer and M Shing and X Pivot and {SafeHer Study Group} and Michele Aieta",
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T1 - Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer

T2 - SafeHer phase III study's primary analysis of 2573 patients

AU - Gligorov, J

AU - Ataseven, B

AU - Verrill, M

AU - De Laurentiis, M

AU - Jung, K H

AU - Azim, H A

AU - Al-Sakaff, N

AU - Lauer, S

AU - Shing, M

AU - Pivot, X

AU - SafeHer Study Group

AU - Aieta, Michele

N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.

PY - 2017/9

Y1 - 2017/9

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 - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents

KW - Breast Neoplasms

KW - Chemotherapy, Adjuvant

KW - Female

KW - Humans

KW - Injections, Subcutaneous

KW - Middle Aged

KW - Receptor, ErbB-2

KW - Survival Analysis

KW - Trastuzumab

KW - Young Adult

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

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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

ER -