| Eligibility |
Inclusion Criteria:
1. Histologically diagnosed as breast cancer (invasive cancer).
2. Histologically diagnosed as hormone receptor positive (at least one of ER and PgR is
positive) and HER2 negative. However, if there are multiple specimens, the
histological results of the most recent specimen that meets the eligibility criteria
1. and 2. should be used.
3. Diagnosed with advanced recurrent breast cancer (either unresectable locally advanced
breast cancer, recurrent breast cancer, or Stage IV breast cancer).
4. Age 20 years or older on the date of registration. Either male or female are
acceptable.
5. ECOG performance status (PS) of 0-2.
6. Patients must have measurable lesions.
7. Hormone refractory[*a] or life-threatening metastases [*b].
1. Hormone refractory: Recurrence within 2 years after the start of postoperative
endocrine therapy, or progression within 6 months of endocrine therapy for
advanced recurrent breast cancer.
2. Life-threatening metastases: Symptomatic metastases that require symptomatic
relief through urgent tumor shrinkage. Examples include multiple liver
metastases, lung metastases, carcinomatous pleurisy, and carcinomatous
lymphangitis.
8. PD-L1 status has been confirmed by a central measurement institute.
9. No active brain metastases that require treatment.
10. No history of prior chemotherapy treatment for advanced or recurrent breast cancer.
However, in case that a history of preoperative/postoperative chemotherapy including
paclitaxel or docetaxel, it is acceptable if at least 6 months have passed since the
last dose.
11. The most recent laboratory test within 14 days prior to enrollment (the same day of
the week two weeks prior to the date of enrollment is acceptable) must meet all of the
following
1. Neutrophil count =1,500/mm^3
2. Hemoglobin = 9.0 g/dL (No blood transfusion within 14 days prior to the date of
blood collection for the test used for registration)
3. Platelet count =10×104/mm^3
4. Total bilirubin = 1.5 mg/dL
5. AST = 100 IU/L (= 150 IU/L if liver metastasis is present)
6. ALT = 100 IU/L (= 150 IU/L in case of liver metastasis)
7. Serum creatinine =1.2 mg/dL
8. PT-INR = 1.5, but PT-INR = 3.0 if the patient is taking anticoagulants such as
warfarin prophylactically.
9. Urine protein (test paper method) of 1+ or less
12. For women of childbearing potential [*a], consent for contraception from the time of
obtaining consent until at least 6 months after completion of the protocol treatment.
For lactating patients, the patient agrees not to breastfeed from the start of
protocol treatment until at least 6 months after the end of protocol treatment. For
men, they agree to use contraception from the start of protocol treatment until at
least 6 months after the end of protocol treatment [*b].
1. Women of childbearing potential: Women who have experienced menarche, have not
undergone sterilization (hysterectomy or bilateral oophorectomy), and have not
undergone menopause. Menopause is defined as the absence of menstruation for more
than 12 months without another medical reason such as drug administration.
2. Examples of contraceptive methods: condoms, pessaries, oral contraceptives, use
of intrauterine devices, etc.
13. The patient's written consent to participate in the study has been obtained.
Exclusion Criteria:
1. Active multiple cancer. However, the following are excluded: ?Completely resected
cancers: basal cell carcinoma, Stage I spinous cell carcinoma, intraepithelial
carcinoma, intramucosal carcinoma, superficial bladder cancer, ? gastrointestinal
tract cancer that has been curatively resected by ESD or EMR, and ? other cancers that
have not recurred for more than 5 years.
2. Infectious diseases that require systemic treatment.
3. Complicated active gastrointestinal ulcer.
4. Patients must have poorly controlled hypertension (systolic blood pressure =150 mmHg
and/or diastolic blood pressure =100 mmHg) despite the use of two or more
antihypertensive agents.
5. Patients must have symptomatic congestive heart failure, unstable angina, or
arrhythmia requiring treatment at the time of enrollment.
6. History of myocardial infarction within 1 year prior to enrollment.
7. Major surgery or incisional biopsy or significant trauma within 28 days prior to
enrollment; placement of a CV port is not considered major surgery.
8. Patients with deep vein thrombosis or pulmonary embolism at the time of enrollment, or
a history of such within 1 year prior to enrollment.
9. Use of anticoagulants (except aspirin of 324 mg/day or less) within 10 days prior to
enrollment.
10. Patients with a history of idiopathic pulmonary fibrosis, organizing pneumonia
(bronchiolitis obliterans, etc.), drug-induced pneumonitis, or idiopathic pneumonitis.
However, patients with a history of drug-induced pneumonitis who are asymptomatic at
the time of enrollment can be enrolled if they undergo regular chest X-ray
examinations and careful follow-up including auscultation and medical examination.
11. Findings of active pneumocystitis on chest CT. However, a history of localized
radiation pneumonitis (fibrosis) in the irradiation field is inclusible.
12. Patients have been treated with investigational atezolizumab, or other immune
checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody drugs), or
immunostimulants (e.g., interferon, interleukin-2).
13. Active autoimmune disease, immunodeficiency, or history thereof (e.g., myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
etc.). However, the following are inclusible. Patients with autoimmune hypothyroidism
who are using a stable dose of thyroid hormone preparations. Patients with eczema,
psoriasis, lichen simplex chronicus, or vitiligo vulgaris whose symptoms are limited
to the skin, and whose rash accounts for less than 10% of the body surface area and is
well controlled by topical application of low potency corticosteroids alone. No acute
exacerbation of the underlying disease requiring solaren long-wavelength ultraviolet
therapy, methotrexate, retinoids, biologics, oral calcineurin inhibitors, high potency
or oral corticosteroids within the past 12 months.
14. Patients who have received a live attenuated vaccine within 4 weeks prior to
enrollment or are expected to require a live attenuated vaccine within 5 months of
completion of protocol treatment.
15. Patients have not recovered from clinically significant toxicity caused by previous
therapy, except for alopecia and Grade 1 peripheral neuropathy.
16. Hypersensitivity or contraindication to any component of the therapeutic agent,
including macrogol glycerol ricinoleate (Cremophor®), an additive to paclitaxel.
17. Positive for HIV antibodies, HBs antigen, or HCV antibodies (however, if HCV
antibodies are positive but HCV-RNA is not detected, it is not excluded).
18. Negative for HBs antigen, positive for HBs antibody or HBc antibody, and positive for
HBV-DNA quantification.
19. Women who are pregnant, lactating, or may be pregnant.
20. Patients with psychosis or psychiatric symptoms that interfere with daily life and are
judged to be difficult to participate in the study.
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