Results From the First Multicenter, Open-label, Phase IIIb Study Investigating the Combination of Pertuzumab With Subcutaneous Trastuzumab and a Taxane in Patients With HER2-positive Metastatic Breast Cancer (SAPPHIRE).

INTRODUCTION The primary objective of this study was to assess the safety and tolerability of combination pertuzumab, subcutaneous trastuzumab (Herceptin), and investigator's choice of taxane chemotherapy in previously untreated patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Efficacy was a secondary objective. PATIENTS AND METHODS This study was an open-label, non-randomized study of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who had no previous systemic non-hormonal anti-cancer therapy for metastatic disease. The primary endpoints included adverse events (AE), serious AEs, and cardiac AEs. Secondary endpoints included overall response rate, progression-free survival, and overall survival. Patients were treated with pertuzumab and subcutaneous trastuzumab in 3-weekly cycles with taxane chemotherapy until disease progression, unacceptable toxicity, or withdrawal of consent and followed for a minimum of 24 months from initiation of study treatment. RESULTS Fifty patients were enrolled and included in the analysis. All patients experienced at least 1 AE, with diarrhea, fatigue, peripheral neuropathy, alopecia, rash, and nausea the most common. Three patients experienced at least 1 grade 3 event of suspected cardiac origin (cardiac failure, cardiomyopathy, hypertension). Six patients withdrew from therapy owing to AEs (cardiac failure, drug hypersensitivity, decreased left ventricular ejection fraction, syncope, and bullous dermatitis). Taxane chemotherapy comprised nab-paclitaxel (74.0% of patients), docetaxel (28.0%), or paclitaxel (4.0%). The overall response rate was 73.3% (95% confidence interval, 58.1%-85.4%), the median progression-free survival was 17.0 months (95% confidence interval, 12.5-31.2 months), and the median overall survival was not reached. CONCLUSIONS Subcutaneous trastuzumab in this combination has an acceptable safety and tolerability profile, including cardiac safety profile. Safety and efficacy appear similar to previous studies of intravenous trastuzumab in this combination.

• Publication year

  2019

• Venue

  Clinical Breast Cancer

• Publication date

  2019-06-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/J.CLBC.2019.02.008PMID 30922805
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Subcutaneous trastuzumab (H SC) with intravenous pertuzumab (P IV) and docetaxel (D IV) in HER2-positive advanced breast cancer (BC): MetaPHER second interim analysis.

  2018cited by this paper
• Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study.

  2017cited by this paper
• Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results

  2016cited by this paper
• Association of clinical benefit rate (CBR) with survival: A pooled-analysis of metastatic breast cancer (MBC) trials submitted to the U.S. Food and Drug Administration (FDA).

  2016cited by this paper
• Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study.

  2015cited by this paper
• 1816 Preliminary safety results from PERUSE, a study of 1436 patients (pts) treated with first-line pertuzumab (P) combined with trastuzumab (H) and taxane therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC)

  2015cited by this paper
• Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.

  2015cited by this paper
• Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study.

  2013cited by this paper
• Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study.

  2013cited by this paper
• Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

  2013cited by this paper
• Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial.

  2012cited by this paper
• In the end what matters most? A review of clinical endpoints in advanced breast cancer.

  2011cited by this paper
• Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.

  2004cited by this paper

• Cardiotoxic Effects of Antibody Drug Conjugates vs Standard Chemotherapy in ERBB2-Positive Advanced Breast Cancer

  2025cites this paper
• HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future

  2024cites this paper
• A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer

  2024cites this paper
• A patient-led survey on information and communication needs of patients with metastatic breast cancer in Ireland and Northern Ireland (CTRIAL-IE 23–05)

  2024cites this paper
• Emerging Targeted Therapies for HER2-Positive Breast Cancer

  2023cites this paper
• An Open-Label, Multinational, Multicenter, Phase IIIb Study with Subcutaneous Administration of Trastuzumab in Patients with HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction.

  2022cites this paper
• Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Guideline Update

  2022cites this paper
• Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

  2022cites this paper
• Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery

  2021cites this paper
• The challenge of value-based pricing in combination therapy: the case of trastuzumab and pertuzumab in HER2+ metastatic breast cancer

  2021influential citation
• Subcutaneous trastuzumab with pertuzumab and docetaxel in HER2-positive metastatic breast cancer: Final analysis of MetaPHER, a phase IIIb single-arm safety study

  2021cites this paper
• Cost-efficiency and expanded access modeling of conversion to biosimilar trastuzumab-dkst with or without pertuzumab in metastatic breast cancer

  2021cites this paper
• Extrapolation: experience gained from original biologics.

  2021cites this paper
• 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.

  2021cites this paper
• An Attribution of Value Framework for Combination Therapies

  2021cites this paper
• Subcutaneous Trastuzumab with Pertuzumab and Docetaxel in HER2-Positive Metastatic Breast Cancer: Final Analysis of MetaPHER, A Phase 3b Single-Arm Safety Study

  2020cites this paper
• Trastuzumab/Hyaluronidase-oysk: A New Option for Patients With HER2-Positive Breast Cancer

  2020cites this paper
• Development of a Subcutaneous Fixed‐Dose Combination of Pertuzumab and Trastuzumab: Results From the Phase Ib Dose‐Finding Study

  2018cites this paper
• Development of New Formulations of Biologics: Expectations, Immunogenicity, and Safety for Subcutaneous Trastuzumab

  2018cites this paper
• nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings

  2017cites this paper