HER2-positive Breast Cancer, Stage I Breast Cancer
Conditions
Keywords
Breast Cancer, Her2-positive, Pertuzumab, Trastuzumab, Omission surgery
Brief summary
This is a prospective, single arm, open-label, unicenter, exploratory study in women with primary operable HER2-positive, HER2-enriched/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab. The primary trial objective is to estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging (i.e. Magnetic resonance imaging) and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.
Interventions
BIOLOGICALTrastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination
After 13 weeks of neoadjuvant treatment, a breast MRI will be performed. If a complete response is observed on breast MRI, patients will undergo a stereotactic-guided VAB of the marker area to obtain 12 cylinders of breast parenchyma, which is equivalent to 2 grams of tissue. If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB, patients will be eligible to omit loco-regional surgery.
Sponsors
SOLTI Breast Cancer Research Group
Roche Pharma AG
Fundacio Clinic Barcelona
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer. 2. A participant is eligible to participate if she is not pregnant, not breastfeeding. 3. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 4. Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics: * HER2-positive status by local determination according to 2018 ASCO/CAP guidelines. * PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination. * Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component) * Tumor largest diameter ≤4 cm as defined by breast MRI. * No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible. * No evidence of distant metastasis (M0) by routine clinical assessment. 5. Patient must have known ER and PR status locally determined prior to study entry. 6. Eligible for taxane therapy. 7. Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy. 8. Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer. 9. Breast cancer eligible for primary surgery 10. Have provided archival tumor tissue sample or newly obtained core. Formalin-fixed,paraffin embedded (FFPE) tissue blocks are mandatory. Available pre-treatment FFPE core biopsy evaluable for PAM50 or possibility to obtain one. 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 12. Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol. 13. Have adequate organ function.
Exclusion criteria
1. Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer. 2. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel. 3. Clinical stage II, III or IV. 4. History of radiotherapy in the ipsilateral breast or axilla. 5. History of surgery of the ipsilateral axilla. 6. Bilateral invasive breast cancer. 7. Infiltrating lobular carcinoma. 8. Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast. 9. Patients who have undergone sentinel lymph node biopsy prior to study treatment. 10. Patient has active cardiac disease or a history of cardiac dysfunction 11. Has an active infection requiring systemic therapy. 13\. Patients with a history of previous breast cancer are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival at 3years | 3 years | To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pCR Rate | pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy | rate of pathological complete response (pCR) between the treatment groups by HR status |
| Patient Reported Outcomes (Global Health Status) | The questionnaire was filled by the patients at screening and post adjuvant therapy. | The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL). The measure consists of five functional scales (physical, role, cognitive, emotional, and social). For this study, raw scores were used without any transformation. The functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much). Higher scores indicate worse functioning. To assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment. The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent). Scoring method: GHS = (Q29 + Q30) / 2 Raw score range: Minimum = (1 + 1) / 2 = 1; Maximum = (7 + 7) /2 = 7 |
Countries
Spain
Participant flow
Recruitment details
Overall, 20 patients were screened for the study in a single study centre (clinical setting) over the duration of 18 months. A total of 5 patients were finally selected for the study treatment after meeting all the inclusion criteria and signing the ICF
Pre-assignment details
Out of 20 patients screened, 13 patients did not fulfill the study criteria (PAM50 subtype other than HER2-Enriched, ERBB2 high, liver metastasis, multicentric tumor). Finally only 5 patients that fulfilled all eligibility criteria and signed the ICF were included
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):
* Tumor size ≤ 2 cm: Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease)
* Tumor size \> 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel/trastuzumab/pertuzumab (TDM-1 if residual disease) | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up after 1 year | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Customized >= 40 yrs | 5 participants |
| ECOG baseline Grade 0 | 4 participants |
| ECOG baseline Grade 1 | 1 participants |
| Menopausal Status Postmenopausal (min 12 mnths without menses before neoadyuvance treatment) | 4 participants |
| Menopausal Status premenopausal | 1 participants |
| Previous cancer history No | 5 participants |
| Previous cancer history Yes | 0 participants |
| Race/Ethnicity, Customized Caucasian | 5 participants |
| Region of Enrollment Spain | 5 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 3 |
Outcome results
Primary
Disease-free Survival at 3years
To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.
Time frame: 3 years
Population: After completion of neoadjuvant therapy with paclitaxel and Trastuzumab/pertuzumab, out of 5 patients, only 3 patients showed complete response (assessed by MRI) and 2 patients (no stereo-guided VAB assessment) did not undergo surgery. However, the participants were lost to follow-up before 3-year assessments, so no evaluable 3-year survival data are available
Secondary
Patient Reported Outcomes (Global Health Status)
The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL). The measure consists of five functional scales (physical, role, cognitive, emotional, and social). For this study, raw scores were used without any transformation. The functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much). Higher scores indicate worse functioning. To assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment. The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent). Scoring method: GHS = (Q29 + Q30) / 2 Raw score range: Minimum = (1 + 1) / 2 = 1; Maximum = (7 + 7) /2 = 7
Time frame: The questionnaire was filled by the patients at screening and post adjuvant therapy.
Population: Out of the treatment population, 3 patients underwent surgery post neoadjuvant therapy (standard therapy) and 2 patients did not undergo surgery (investigative therapy). All the patients of both the groups completed the patient reported outcomes questionaire at screening. 1 patient from the patient group that underwent surgery did not complete the questionnaire after adjuvant therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Omision of Surgery (Complete Response) | Patient Reported Outcomes (Global Health Status) | 5 score on a scale |
| HR Negative | Patient Reported Outcomes (Global Health Status) | 4 score on a scale |
| Patients With Omission of Surgery (Assessment at Screening) | Patient Reported Outcomes (Global Health Status) | 5.25 score on a scale |
| Patients With Omission of Surgery (Assessment After Adjuvant Therapy) | Patient Reported Outcomes (Global Health Status) | 5 score on a scale |
Secondary
pCR Rate
rate of pathological complete response (pCR) between the treatment groups by HR status
Time frame: pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy
Population: While total number of HR positive patients and HR negative patients in the overall treatment group is 2 and 3 respectively, only 1 patient in the former and 2 patients in the later group were evaluated for pCR at surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omision of Surgery (Complete Response) | pCR Rate | 0 Participants |
| HR Negative | pCR Rate | 2 Participants |