Atezolizumab With Nab-paclitaxel for Patients With Triple-negative Stage IV Breast Cancer

The study will evaluate the therapeutic efficacy of the association of Atezolizumab plus nabPaclitaxel in a real life context, in order to document any differences both in terms of activity and safety with respect to the knowledge of the association reported in the literature

Inclusion Criteria:Women aged ≥ 18 years who have provided written informed consentMetastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)No prior chemotherapy, experimental or targeted systemic therapy for inoperable locally advanced or metastatic TNBC. Prior chemotherapy (including taxanes) in the neoadjuvant or adjuvant setting is allowable if treatment was completed ≥12 months prior to enter the compassionate use programPD-L1-positive tumour status defined as PD-L1 expression ≥1% on tumour-infiltrating immune cells as percentage per tumour area, assessed by the Ventana PD-L1 (SP142) assay based on the status of the primary tumor and/or the biopsy of metastatic disease before starting the treatment. Samples should be assessed by a qualified laboratory and different assays are not acceptablePatients eligible for ongoing atezolizumab clinical trials from which they may benefit are excludedEligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)ECOG performance status of 0 or 1Life expectancy ≥ 12 weeksMeasurable disease, as defined by RECIST v1.1Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1)ANC ≥1500 cells/µL (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks prior to Cycle 1, Day 1);Lymphocyte count ≥500/µL; Platelet count ≥100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1);Hemoglobin ≥9.0 g/dL; AST, ALT, and alkaline phosphatase ≤2.5x the upper limit of normal (ULN), with the following exceptions:Patients with documented liver metastases: AST and ALT ≤5x ULNPatients with documented liver or bone metastases: alkaline phosphatase ≤ 5x ULNSerum bilirubin ≤1.25x ULN (patients with known Gilbert disease who have serum bilirubin level ≤3x ULN may be enrolled)INR and aPTT ≤1.5x ULN (this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose)Calculated creatinine clearance ≥30 mL/minAbsence of a positive test for HIV, active hepatitis B or hepatitis C, active tuberculosisAbsence of significant cardiovascular disease (New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to treatment start, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) <40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate)No known untreated, symptomatic or corticosteroid-dependent brain metastasesPatients with any history of immune deficiencies or autoimmune disease are excluded from the treatment. Possible exceptions could be autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone, controlled type 1 diabetes mellitus on a stable insulin dosing regimen, eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations onlyPatients must not be administered systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to start the treatmentPatients must agree not to receive live, attenuated vaccine (e.g., FluMist®) within 28 days prior to the first dose of study treatment (Cycle 1, Day 1), during treatment, or within 5 months following the last dose of atezolizumabNo known hypersensitivity or allergy to nab-paclitaxel, to any of the excipients, to biopharmaceuticals produced in Chinese hamster ovary cells, or to any component of the atezolizumab formulationPregnancy or lactation are general medical exclusion criteria from the treatmentWomen of child bearing potential must agree to either use a contraceptive method with a failure rate of ≤ 1% per year or to remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 5 months after the last dose of atezolizumab or 1 month after the last dose of nab-paclitaxel, whichever is later. For definition of postmenopausal status see the study protocolWomen of child bearing potential must have a negative serum pregnancy test result prior to start the treatmentEsclusion Criteria:Patients who have not completed 1 cycle of treatment