Center for Global Research Data

Summarising the therapeutic and adverse effects of antibody-drug conjugates in older women with breast cancer: A review of clinical trial individual-participant data

Lead Investigator: Ashley Hopkins, Flinders University
Title of Proposal Research:  Summarising the therapeutic and adverse effects of antibody-drug conjugates in older women with breast cancer: A review of clinical trial individual-participant data
Vivli Data Request: 8056
Funding Source: Ashley Hopkins is EL1 Investigator with funding from the National Health and Medical Research Council of Australia. Employment Contracts: Flinders University.
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Over the last decade there has been substantial advancements in the treatment of breast cancer, including the introduction of the antibody-drug conjugates ado-trastuzumab emtansine, sacituzumab govitecan-hziy, and fam-trastuzumab deruxtecan-nxki. Antibody-drug conjugates or ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents. While these are important advancements, response and toxicity to these medicines remains variable between patients. One factor requiring investigation is the frequencies of therapeutic and adverse effects according to age groups, particularly, in older patients. The treatment of breast cancer in older adults can be challenging due to symptoms of frailty and comorbidities. Despite breast cancer frequently occurring in older patients (e.g., >45% of cases occur in women aged >65 years and >20% in women aged >75 years), the understanding of the efficacy and tolerability of emerging antibody-drug conjugates in older patients with breast cancer is limited.

This project will bring together individual-participant data from clinical trials evaluating the use of antibody-drug conjugates in patients with breast cancer to summarise and review the therapeutic and adverse effects according to age. While some clinical trials report exploratory analysis of treatment efficacies of antibody-drug conjugates in women aged >60 years, systematic evaluations across the range of patient ages are not available. Further, data on adverse events frequencies according to age groups have not been reported. Being able to provide clinicians and patients quality information on the observed response and adverse effect profiles of antibody-drug conjugates in older patients with breast cancer will enable better patient-centred decisions and inform future clinical trial designs. Due to the recency of registration of these medicines an ability to explore the efficacy and tolerability of emerging antibody-drug conjugates in older patients with breast cancer via real-world data sources is limited, and thus transparently shared clinical trial data represents an important opportunity to aid filling this clinical knowledge gap.

Requested Studies:

A Randomized, Multicenter, Phase III Open-label Study of the Efficacy and Safety of Trastuzumab MCC-DM1 vs. Capecitabine + Lapatinib in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy
Data Contributor: Roche
Study ID: NCT00829166
Sponsor ID: BO21977

A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy
Data Contributor: Roche
Study ID: NCT01772472
Sponsor ID: BO27938

A Phase III Randomized, Multicenter, Two Arm, Open-label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared With Treatment of Physician’s Choice in Patients With HER2-positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2 Directed Therapy
Data Contributor: Roche
Study ID: NCT01419197
Sponsor ID: BO25734

A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT01120184
Sponsor ID: BO22589