Adjuvant Systemic Treatment for Oestrogen-receptor (ER)-Positive HER2-negative Breast Carcinoma in Women Over 70 According to Genomic Grade (GG): Chemotherapy + Endocrine Treatment Versus Endocrine Treatment. A French UNICANCER Geriatric Oncology Group (GERICO) and Breast Group (UCBG) Multicentre Phase III Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- UNICANCER
- Enrollment
- 1,989
- Locations
- 115
- Primary Endpoint
- Overall survival
Study Overview
Brief Summary
The purpose of the study is to evaluate the benefit of adjuvant chemotherapy on overall survival for elderly patients with breast cancer, in a sub group with a high risk of relapse according to Genomic Grade test.
Detailed Description
The purpose of this trial is to address the question of the added value of adjuvant chemotherapy on survival in 70+ BC patients with ER+ disease, deemed "at risk of relapse" (pN+ or pN0 with a high prognostic classifier, namely GG by RT-PCR) and planned to receive as well adjuvant endocrine treatment. This benefit will be weighed with the competition exerted by comorbidities on mortality.
As in many recently developed trials evaluating specific strategies for the elderly (e.g. CALGB 49907 (8); bevacizumab and colorectal cancer in the PRODIGE 20 elderly program supported by the PHRC 2010), the choice of chemotherapy regimen will be left to the investigator between 3 "standard" ones: TC x 4 (no anthracyclines), AC x 4 or MC x 4 (better cardiac tolerance), in order to obtain enrolment of a less highly selected population, more representative of the general population to the difference of the high selection classically observed in standard oncology trials.
In parallel, patients not included in the randomized part (whatever reason) and treated with adjuvant endocrine treatment only will be followed up as a separate observational cohort.
- Screening All women 70+ having undergone surgery for invasive pN0 or pN+, ER+ HER2- BC, will be screened and invited to participate. Pre-selection will be possible pre-operatively.
- Prognostic signature After having signed a written informed consent, the prognostic signature Genomic Grade (GG) will be assessed by RT-PCR.
- Randomization (Group I) Only the patients with a Genomic Grade (GG) considered as high will be randomized (1:1): endocrine treatment only (Arm A) versus endocrine treatment + adjuvant chemotherapy (Arm B).
Randomization1:1 between arm A and B will be done using minimization stratified according to pN status (pN+ vs pN0), G8 (≤ vs > 14), and center.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Women aged ≥ 70 yo,
- •Histologically proven invasive breast cancer (regardless of the type),
- •Complete surgery performed before enrolment: radical modified mastectomy or breast conservative surgery, with either a sentinel lymph node procedure or axillary lymph node dissection,
- •Any N status (pN+ or pN0),
- •No clinically or radiologically detectable metastases (M0),
- •Oestrogen receptor (ER)-positive, as defined by a ≥ 10% tumor stained cells by immunohistochemistry (IHC),
- •HER2 negative status (i.e. IHC score 0 or 1+, or IHC score 2+ and FISH/SISH/CISH negative),
- •Normal haematological function: ANC ≥ 1,500/mm3; platelets count ≥ 100,000/mm3; haemoglobin > 9 g/dl,
- •Normal hepatic function: total bilirubin ≤ 1.25 ULN; ASAT and ALAT ≤ 1.5 ULN; alkaline phosphatases ≤ 3 ULN,
- •Creatinine clearance (MDRD formula) ≥ 40 mL/min,
- •PS (ECOG) ≤ 2,
- •Patient able to comply with the protocol,
- •Patients must have signed a written informed consent form prior to any study specific procedures, including the agreement for the use of archived tumoral material for genomic screening and data collection,
- •Patients must be affiliated to a Social Health Insurance.
Exclusion Criteria
- •Any metastatic impairment, including homolateral sub-clavicular node involvement, regardless of its type,
- •Any tumor ≥ T4a (UICC1987) (cutaneous invasion, deep adherence, inflammatory breast cancer),
- •ER-negative breast cancer (i.e. <10% tumor stained cells by IHC),
- •HER2 overexpression, defined as IHC score 3+ or score 2+ and FISH/SISH/CISH positive,
- •Any chemotherapy, hormonal therapy or radiotherapy for breast cancer before surgery,
- •PS (ECOG) ≥ 3,
- •Any specific contra-indication to the study drugs (including but not limited to hypersensitivity to the study drugs or their components),
- •Patient deprived of freedom or under tutelage,
- •Patient unable to comply with the required medical follow-up for geographic, social or psychological reasons.
Arms & Interventions
Arm A: ENDOCRINE TREATMENT
HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).
Intervention: HORMONOTHERAPY (Drug)
Arm B: CHEMOTHERAPY + ENDOCRINE TREATMENT
HORMONOTHERAPY (Tamoxifen, aromatase inhibitor or sequential hormonotherapy) is left to the investigator judgement in both groups (I and II).
CHEMOTHERAPY regimen will be chosen amongst the following ones:
- TC (docetaxel + cyclophosphamide)
- AC (doxorubicin + cyclophosphamide)
- MC (liposomal non pegylated doxorubicin [Myocet®]+ cyclophosphamide)
Intervention: CHEMOTHERAPY then HORMONOTHERAPY (Drug)
Outcomes
Primary Outcomes
Overall survival
Time Frame: Median follow-up = 4 years
The OS is defined as the interval between the date of randomization and the date of death from any cause.
Secondary Outcomes
- Four-Year Mortality Index for Older Adults(Lee Score)(At the inclusion)
- Event-free survival (ESF)(median follow-up = 4 years)
- Acute and late toxicity during the study(Throughout treatment completion, up to 4 years)
- Quality of life questionnaire - Elderly cancer patients (QLQ-ELD15)(At baseline, week 16, 5 months, 6 months, 1 year, 2 years, 3 years, and 4 years)
- Usefulness of GG by RT-PCR(two weeks after surgery (local histo. and GG test) then after inclusions are performed (central histo.))
- Specific overall survival(median follow-up = 4 years)
- Disease-free survival (DFS)(median follow-up = 4 years)
- Geriatric Assessment(at the end of the chemotherapy in arm B or 16 weeks after the randomization in arm A (endocrine treatment only), and then each year during a 4-year follow-up period, for both arms)
- Quality of life questionnaire - Core 30 (QLQ-C30)(At baseline, week 16, 5 months, 6 months, 1 year, 2 years, 3 years, and 4 years)
- Cost-effectiveness analysis(at the end of the chemotherapy in arm B or 16 weeks after randomization in arm A, and then each year during a 4-year follow-up period, for both arms of the group I.)