Fam-trastuzumab deruxtecan-nxki

(Enhertu®)

Fam-trastuzumab deruxtecan-nxki

Drug updated on 9/4/2024

Dosage FormInjection (intravenous; 100 mg/vial)
Drug ClassHER2-directed antibodies and topoisomerase inhibitor conjugates
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
  • Indicated for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.
  • Indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.
  • Indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
  • Indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.

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Summary
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  • Enhertu (fam-trastuzumab deruxtecan-nxki) is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. It is also indicated for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Additionally, it is used for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. Furthermore, it is indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. Finally, it is used for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.
  • This summary is based on the review of 51 systematic review(s)/meta-analysis(es). [1-51]
  • Objective Response Rate (ORR) and Pathological Complete Response (pCR): Trastuzumab deruxtecan (T-DXd) demonstrated an ORR between 37% and 79.9% across various studies in HER2-positive breast cancer and other solid tumors. Comparatively, pyrotinib with trastuzumab and chemotherapy achieved a pCR rate of 57%.
  • Progression-Free Survival (PFS) and Overall Survival (OS): In HER2-positive patients with brain metastases, T-DXd showed a median PFS of 15 months with an ORR of 61%. Additionally, meta-analysis results indicated that T-DXd improved PFS (OR: 0.38) and OS (OR: 0.61) across various solid tumors.
  • Health-Related Quality of Life (HRQoL): Trastuzumab-containing regimens were associated with improved HRQoL during treatment, with post-treatment HRQoL being comparable to chemotherapy but showing better functional status and reduced fatigue.
  • Subgroup Efficacy: T-DXd demonstrated effectiveness in HER2-low expressing tumors, with ORRs of 46% in HER2-low and 64% in HER2-positive expressions. In hormone receptor-positive/HER2-positive breast cancer, dual HER2 blockade combined with endocrine therapy provided superior PFS benefits.
  • Common adverse events (AEs) associated with enhertu (fam-trastuzumab deruxtecan-nxki) included gastrointestinal toxicities such as nausea, vomiting, and diarrhea, as well as hematologic toxicities including neutropenia, anemia, and fatigue.
  • Interstitial lung disease (ILD) was a significant safety concern, with incidences reported up to 10.9% in clinical trials.
  • In comparison to other HER2-targeted therapies, T-DXd demonstrated similar or slightly higher incidences of AEs, particularly neutropenia and anemia.
  • Serious adverse events (SAEs) were significant, with grade ≥3 AEs such as severe neutropenia and anemia being the most common in patients treated with T-DXd.
  • T-DXd demonstrated significant effectiveness in specific subgroups, including patients with breast cancer brain metastases (BCBM), hormone receptor-positive/HER2-positive tumors, and HER2-low expressing tumors, with notable improvements in ORR and PFS.
  • Clinical management should focus on monitoring ILD/pneumonitis and cardiotoxicity, particularly in patients receiving T-DXd or combination regimens involving trastuzumab and anthracyclines, due to the increased risks observed in these subgroups.

Product Monograph / Prescribing Information

Document TitleYearSource
Enhertu (fam-trastuzumab deruxtecan-nxki) Prescribing Information.2024Daiichi Sankyo Inc., Basking Ridge, NJ

Systematic Reviews / Meta-Analyses

Document TitleYearSource
A systematic review of health-related quality of life in women with HER2-positive metastatic breast cancer treated with trastuzumab.2024PharmacoEconomics
Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: a systematic review and meta‑analysis.2024Oncology Letters
Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: a systematic review and meta-analysis.2024ESMO Open
Efficacy and safety of first-line therapy in patients with HER2-positive advanced breast cancer: a network meta-analysis of randomized controlled trials.2024Journal of Cancer Research and Clinical Oncology
Efficacy and safety of trastuzumab deruxtecan in breast cancer: a systematic review and meta-analysis.2023Clinical Breast Cancer
ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis.2023Heart Failure Reviews
The value of neoadjuvant anthracycline-based regimens for HER2-positive breast cancer: a systematic review and meta-analysis including 1366 patients.2023Clinical Medicine Insights
Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: a systematic review and meta-analysis.2023Radiotherapy and Oncology
Landscape of neoadjuvant therapy in HER2-positive breast cancer: a systematic review and network meta-analysis.2023European Journal of Cancer
Efficacy and safety of trastuzumab deruxtecan in patients with solid tumors: a systematic review and meta-analysis of 3 randomized controlled trials.2023American Journal of Cancer Research
The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-expressing solid tumours: a single-arm meta-analysis.2023Japanese Journal of Clinical Oncology
Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis.2023Frontiers in Pharmacology
Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.2023The Breast
Identifying the optimal therapeutics for patients with hormone receptor-positive, HER2-positive advanced breast cancer: a systematic review and network meta-analysis.2023ESMO Open
Pathologic complete response achieved in early-stage HER2-positive breast cancer after neoadjuvant therapy with trastuzumab and chemotherapy vs. trastuzumab, chemotherapy, and pertuzumab: a systematic review and meta-analysis of clinical trials.2023Cureus
Health-related quality of life in HER2-positive early breast cancer woman using trastuzumab: a systematic review and meta-analysis.2023Frontiers in Pharmacology
Adjuvant treatment with trastuzumab of patients with HER2-positive, T1a-bN0M0 breast tumors: a systematic review and meta-analysis.2023Critical Reviews in Oncology/Hematology
Neoadjuvant therapy with vs. without anthracyclines for HER2-positive breast cancer: a systematic review and meta-analysis.2023Frontiers in Oncology
Comparison of the efficacy and safety of third-line treatments for advanced gastric cancer: a systematic review and network meta-analysis.2023Frontiers in Oncology
Treatment-related adverse events associated with HER2-Targeted antibody-drug conjugates in clinical trials: a systematic review and meta-analysis.2022eClinicalMedicine
Axillary downstaging and the impact of clinical axillary status on efficacy of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis.2022Technology in Cancer Research & Treatment
Lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy for HER2 positive breast cancer patients: an updated systematic review and meta-analysis.2022Systematic Reviews
The adverse effects of trastuzumab-containing regimes as a therapy in breast cancer: a piggy-back systematic review and meta-analysis.2022PLOS ONE
Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer.2022Cancer Treatment Reviews
Systemic therapy for patients with HER2-positive breast cancer and brain metastases: a systematic review and meta-analysis.2022Cancers
Pertuzumab combined with trastuzumab compared to trastuzumab in the treatment of HER2-positive breast cancer: a systematic review and meta-analysis of randomized controlled trials.2022Frontiers in Oncology
Trastuzumab combined chemotherapy for the treatment of HER2-positive advanced gastric cancer.2022Medicine
Determining the optimal (neo)adjuvant regimen for human epidermal growth factor receptor 2-positive breast cancer regarding survival outcome: a network meta-analysis.2022Frontiers in Immunology
T-DM1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis.2022BMC Cancer
Comparative effectiveness and tolerability of targeted agents combined with chemotherapy in patients with HER2-positive gastroesophageal cancer: a network meta-analysis.2022Saudi Journal of Gastroenterology
Adjuvant and neoadjuvant breast cancer treatments: a systematic review of their effects on mortality.2022Cancer Treatment Reviews
Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: a meta-analysis of randomized trials.2022ESMO Open
Neoadjuvant and adjuvant treatment of patients with HER2-positive early breast cancer.2022The Breast
Neoadjuvant treatment with HER2-targeted therapies in HER2-positive breast cancer: a systematic review and network meta-analysis.2022Cancers
Safety of trastuzumab deruxtecan: a meta-analysis and pharmacovigilance study.2022Journal of Clinical Pharmacy and Therapeutics
Toward a treatment sequencing strategy: a systematic review of treatment regimens in advanced gastric cancer/gastroesophageal junction adenocarcinoma.2021Oncologist
A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: successes achieved and opportunities ahead.2021Cancer Treatment Reviews
Treatment outcomes among human epidermal growth factor receptor 2 positive breast cancer patients: a systematic review.2021Journal of Oncology Pharmacy Practice
Efficacy and safety of anti-HER2 agents in combination with chemotherapy for metastatic HER2-positive breast cancer patient: a network meta-analysis.2021Frontiers in Oncology
Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials.2021The Lancet Oncology
Methodological quality evaluation of systematic reviews or meta-analysis of trastuzumab-based therapy for breast cancer: a systematic review.2021Medicine Open
Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and Bayesian network analysis.2021Journal of Cancer
The efficacy and safety of additional anti-HER2-targeting drugs in the treatment of HER2-positive advanced breast cancer: a meta-analysis.2021Anticancer Agents in Medicinal Chemistry
A review of fam-trastuzumab deruxtecan-nxki in HER2-positive breast cancer. 2021Annals of Pharmacotherapy
Quality of life during palliative systemic therapy for esophagogastric cancer: systematic review and meta-analysis.2020Journal of the National Cancer Institute
Benefits of adjuvant treatment including trastuzumab in HER2-positive pT1a-bN0M0 breast cancer: a systematic review and meta-analysis.2020Annals of Translational Medicine
Evaluating the clinical effectiveness and safety of various HER2-targeted regimens after prior taxane/trastuzumab in patients with previously treated, unresectable, or metastatic HER2-positive breast cancer: a systematic review and network meta-analysis.2020Breast Cancer Research and Treatment
Lapatinib plus local radiation therapy for brain metastases from HER-2 positive breast cancer patients and role of trastuzumab: a systematic review and meta-analysis.2020Frontiers in Oncology
Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis.2020The Breast
Targeted neoadjuvant therapy in the HER-2-positive breast cancer patients: a systematic review and meta-analysis.2019Onco Targets and Therapy
Clinical efficacy of combination of pertuzumab, trastuzumab, and docetaxel for treatment of patients with HER2-positive breast cancer.2019Medicine Open

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