Immune checkpoint inhibitors given in monotherapy in advanced breast cancer have shown modest benefit in first-line, but very limited efficacy in later lines. Thus, combination therapies are needed. Response following anti-PD1/PD-L1 monotherapy is associated with large survival benefit in the advanced setting. Previous studies of the intrinsic subtypes have shown that Basal-like and HER2-E are associated with higher expression of immune-related genes or higher infiltration of stromal tumor infiltrating lymphocytes compared to the luminal subtypes. Immune infiltration in BC is associated with chemo/antiHER2 responsiveness and potentially benefit from anti-PD-1/PD-L1 inhibitors. In addition, one emerging biomarker of response to anti-PD-1 therapy is the tumor mutational burden (I.e. the total number of mutations per coding area of a tumor genome). The HER2-E and Basal-like profiles have been associated with high mutational burden. A range of studies have been initiated including several phase II/III studies evaluating atezolizumab in combination with different chemotherapeutic compounds routinely used in breast cancer, but none with predefined biomarker beyond the expression of PD-L1 by IHC
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
* Atezolizumab IV 1200 mg in combination with * Trastuzumab sc 600mg or IV 6mg/kg every 3 weeks and * Vinorelbine 25 mg/m² IV or 60 mg/m2 PO on days 1 and 8, every 3 weeks during the first cycle and if there are no toxicity signs dose will be increased to 80 mg/m2 PO o 30 mg/m2 IV.
H. Clínico San Cecilio de Granada
Granada, Andalusia, Spain
Hospital del Mar
Barcelona, Barcelona, Spain
Institut Català d'Oncologia Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Canary Islands, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, La Coruña, Spain
Hospital General Universitario de Alicante
Alicante, Spain
Hospital Clinic de Barcelona
Barcelona, Spain
Hospital Universitari Vall d' Hebron
Barcelona, Spain
Hospital San Pedro de Alcántara
Cáceres, Spain
Hospital de León
León, Spain
...and 5 more locations
Overall Response rate
the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
Time frame: until disease progression or up to 2 years after treatment ends
Overall Response rate in PD-L1+ patients
the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
Time frame: until disease progression or up to 2 years after treatment ends
Clinical Benefit
Clinical Benefit Rate at 24 weeks
Time frame: 24 weeks
Overal survival
Time from the date of allocation to the date of death due to any cause.
Time frame: Until analysis data cutoff, 2 years
Progression free survival
Survival witouth observed progression
Time frame: 24 weeks
Duration of response
time from first documented response until progression
Time frame: 24 weeks
Time to response
time until first documented response
Time frame: 24 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
AEs according to CTCAE v 5.0.
Time frame: until end of treatment / through study completion, an average of 1 year
Overall Response rate in patients with brain metastases at baseline
Patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Time frame: Until disease progression or up to 2 years after treatment ends
Clinical Benefit in patients with brain metastases at baseline
Clinical Benefit Rate at 24 weeks in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Time frame: 24 weeks
Progression free survival in patients with brain metastases at baseline
Survival without observed progression in patients with a history of brain metastases, current brain metastases, or equivocal brain lesions at baseline
Time frame: 24 weeks
Overal survival in patients with brain metastases at baseline
Time from the date of allocation to the date of death due to any cause.
Time frame: Until analysis data cutoff, 2 years
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