Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens.

Study Overview
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Brief Summary
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The objective of this non-interventional study (NIS) is to evaluate tucatinib (TUKYSA®) combined with trastuzumab and capecitabine in adult patients with locally advanced or metastatic HER2-positive breast cancer who have been previously treated with at least two anti-HER2 treatment regimens in a real-world setting,

Detailed Description
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TRACE will collect real-world data on the treatment of tucatinib/trastuzumab/capecitabine in a broad patient population including older patients and patients with more comorbidities as compared to the pivotal trial HER2CLIMB. In contrast to HER2CLIMB, TRACE will also include patients receiving tucatinib/trastuzumab/capecitabine during 1st and 2nd palliative therapy line who were primarily diagnosed with early breast cancer and therefore already have received two prior anti-HER2 based treatment regimens before enrollment. Until today, no reliable data is available for these patient population. TRACE will primarily focus on HRQoL using the validated EORTC QLQ C30 + QLQ-BR23 + EQ-5D-5L questionnaires. Further aims are to evaluate effectiveness and safety in distinct subgroups focusing on effectiveness of tucatinib/trastuzumab/capecitabine in patients who have experienced prior therapies with trastuzumab and neratinib or capecitabine and HER2-targeted TKIs in the neoadjuvant, adjuvant or palliative setting, respectively. Study sites may retrospectively include patients within 9 weeks (corresponds to 3 cycles) after start of study treatment up to 6 months after activation of respective site. Retrospectively included patients may have already completed study treatment or may have already deceased at the time of inclusion.

Official Title
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Tucatinib in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer Who Received at Least Two Prior Anti-HER2 Treatment Regimens: a Multicenter, International, Prospective, Non-interventional Study in Germany and Austria (TRACE)

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: TUKYSA®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older. Histologically confirmed HER2+ breast cancer with HER2 positivity defined as a 3+ score by immunohistochemistry (IHC) or a positive result by in situ hybridization (ISH), optionally combined with a IHC2+ score. Diagnosis of locally advanced or metastatic HER2+ breast cancer, including patients with brain metastases. Prior treatment with at least two prior anti-HER2-based regimens. Decision for treatment with tucatinib in combination with trastuzumab and capecitabine according to current SmPC of tucatinib either in 1st/2nd palliative treatment line (Cohort 1) or 3rd/4th palliative treatment line (Cohort 2). Progression after or intolerance of last systemic anti-HER2-based therapy. Indication for treatment with tucatinib as assessed by the treating physician. Signed written informed consent (only if patient is alive at time of inclusion, not applicable for retrospective inclusion of deceased patients). Knowledge of German language. Other criteria according to current SmPC of tucatinib Exclusion Criteria: Contraindications according to SmPC of tucatinib Participation in an interventional clinical trial within 30 days prior to enrolment or simultaneous participation in an interventional clinical trial. Treatment with tucatinib/trastuzumab/capecitabine (=study treatment) in 5th or higher palliative therapy line. Onset of tucatinib treatment later than 22 days after start of therapy line (in case tucatinib administration is started later than trastuzumab and/or capecitabine for any reason)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>150 patients receiving tucatinib/trastuzumab/capecitabine (=study treatment) in 1st or 2nd palliative therapy line. | Drug: TUKYSA®<br>* tucatinib/trastuzumab/capecitabine according to TUKYSA® SmPC.<br>|
| Cohort 2<br>150 patients receiving tucatinib/trastuzumab/capecitabine (=study treatment) in 3rd or 4th palliative therapy line. | Drug: TUKYSA®<br>* tucatinib/trastuzumab/capecitabine according to TUKYSA® SmPC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to deterioration of EORTC global health scale by at least 10 points | Only for prospectively enrolled patients: Time to deterioration of EORTC global health scale is defined as the time interval between fill-in date of baseline questionnaire and the first decrease in global health scale score ≥ 10-point (compared to baseline). If there was no such decrease, death will serve as event for this analysis, if occurring within 4 months after last filled-in questionnaire. | Baseline, up to 24 months | 
| Changes in the global health scale | Only for prospectively enrolled patients: Changes in global health is provided by descriptive statistics of the EQ-5D-5L index value, the EQ-5D-5L visual analogue scale, the EORTC QLQ-C30 global health scale and all functional and symptom scores of the EORTC questionnaires. | Baseline, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to next systemic treatment (TTNT) | TTNT (time to next systemic treatment) is defined as time from first administration of any study treatment (i.e., tucatinib/trastuzumab/capecitabine treatment) to start of a subsequent systemic antineoplastic therapy or death, whichever comes first. | Baseline, up to 5 years | 
| Time to local intracranial treatment (TLT) | TLT (time to local intracranial treatment) is defined as time from first administration of any study treatment to start of a local intracranial therapy, end of a treatment interruption due to isolated intracranial progression, change of treatment strategy or death, whichever comes first. It will be analyzed for patients with isolated intracranial progression after start of study treatment. | Baseline, up to 5 years | 
| Overall survival (OS) | OS is defined as time from first administration of any study treatment to death from any cause. | Baseline, up to 5 years | 
| Overall response rate (ORR) | ORR is defined as proportion of patients with any response (partial or complete remission) overall. | Baseline, up to 5 years | 
| Duration of response (DOR) | DOR is defined as time from first occurrence of any response (complete or partial remission) to progression or death, whichever comes first. Analysis will be conducted in the subset of patients with any response. | Baseline, up to 5 years | 
| Clinical benefit rate (CBR) | CBR is defined as proportion of patients with complete or partial remission for best response or with stable disease lasting for at least 24 weeks. | Baseline, up to 5 years | 
| Adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE | Adverse events (AEs) and serious adverse events (SAEs) as characterized by type, frequency, severity and seriousness | Baseline, up to 30 days after end of tucatinib treatment | 
| Safety laboratory value: Aspartate aminotransferase (AST) | During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of AST (Aspartate aminotransferase) measured will be documented continously during tucatinib treatment. Baseline levels of AST will be presented using descriptive statistics. | Baseline, up to 30 days after end of tucatinib treatment | 
| Safety laboratory value: Alanine aminotransferase (ALT) | During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of ALT (Alanine aminotransferase) measured will be documented continously during tucatinib treatment. Baseline levels of ALT will be presented using descriptive statistics. | Baseline, up to 30 days after end of tucatinib treatment | 
| Safety laboratory value: bilirubin | During tucatinib administration, safety laboratory will be performed according to routine clinical practice. Laboratory values of bilirubin measured will be documented continously during tucatinib treatment. Baseline levels of bilirubin will be presented using descriptive statistics. | Baseline, up to 30 days after end of tucatinib treatment | 
| Therapy decision making | Frequencies and percentages of parameters affecting therapy choice. | Baseline | 
| Previous antineoplastic Therapies | Frequency/type of previous systemic antineoplastic treatments (neoadjuvant/adjuvant/palliative) | Baseline | 
| Previous anti-HER2 regimens | Frequency and type of previous anti-HER2 based regimens | Baseline | 
| Subsequent antineoplastic therapies | Frequency and type of subsequent systemic antineoplastic therapies | End of treatment, up to 5 years | 
| Local antineoplastic therapies | Frequency and type of local antineoplastic therapies (surgeries, radiotherapies) incl. local intracranial therapies | Baseline, up to 5 years | 
| Details on line of treatment for both cohorts | Cohort 1: frequencies and percentages for line of treatment (1st-line or 2nd-line tucatinib treatment) Cohort 2: frequencies and percentages for line of treatment (3rd-line or 4th-line tucatinib treatment) | Baseline | 
| Treatment Duration | Treatment duration of study treatment in total and per substance | Baseline, up to 5 years | 
| Dose intensity | Dose intensity (absolute and relative) for each substance as prescribed by the treating physician | Baseline, up to 5 years | 
| Dose modifications | Frequency, type and reasons of dose modifications (dose reductions, skipped administrations/delays/interruption) compared to SmPC of tucatinib for each substance. | Baseline, up to 5 years | 
| Therapy management (use of relevant supportive medications) | Frequency of usage of antidiarrheal drugs for prophylaxis and treatment of tucatinib-induced diarrhea | Baseline, up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-positive breast cancer, Tucatinib