Randomized Phase II Trial Evaluating the Efficacy of Paclitaxel+Bevacizumab INDUCtion Followed by at atEzolizumab+Nab-paclitaxel for PD-L1-positive Metastatic Triple Negative Breast Cancer (JBCRG-M10, CMA-0196) (INDUCE Trial)
The objective of this research is to evaluate the efficacy of the treatment strategy to administer atezolizumab + nab-paclitaxel (PTX) following 2 cycles of induction therapy with PTX + bevacizumab (induction treatment strategy) in programmed cell death ligand-1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC) in comparison with the standard atezolizumab + nab-PTX therapy.
• Diagnosed with metastatic recurrent or unresectable advanced TNBC
• Documented PD-L1 positivity (SP142 IC ≥ 1) confirmed by local assessment of the most recent tumor sample or an archival tumor sample.
• In the case of patients who were candidates for curative treatment, the duration from the completion of the curative treatment {date of surgery for primary breast cancer or date of last dose of peri-operative drug therapy (including anthracycline regimen, taxane regimen, anti-PD-(L)1 antibody, capecitabine, poly ADP-ribose polimerase \[PARP\] inhibitors, etc.), whichever is later} to the first local or distant recurrence should be at least 6 months. The date of postoperative radiotherapy is not included in this calculation. The use of anti-PD-(L)1 antibodies is allowed during perioperative drug therapy.
• ECOG PS 0-1
• Female or male aged 18 years or older.
• Histologically or cytologically confirmed TNBC that is ER-negative (\< 10% positive cell occupancy or Allred Proportion score of 0-2), HER2-negative (IHC 1+ or less or FISH/DISH negative) according to ASCO/CAP Criteria 2018 (in the case of IHC2+, negativity is confirmed by FISH/DISH).
• Patients who have not received chemotherapy for metastatic recurrent or unresectable advanced cancer. However, prior treatment with PARP inhibitors for metastatic recurrent or unresectable advanced cancers in patients with pathogenic BRCA variants is allowed.
• Having measurable or non-measurable lesions as assessed by local CT or MRI. Tumor lesions located at a previously irradiated site will be considered evaluable if unequivocal progression is seen after radiation.
• Laboratory tests performed within 14 days before enrollment meet the following criteria \[1\] to \[8\]. However, patients must not have received granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to the date of blood sampling.
⁃ \[1\] Neutrophil count ≥ 1500/mm3 \[2\] Platelet count ≥ 10 x 104/mm3 \[3\] Hemoglobin ≥ 8.0 g/dL \[4\] AST (GOT) ≤ 100 IU/L (≤ 200 IU/L if liver metastasis is present) \[5\] ALT (GPT) ≤ 100 IU/L(≤ 200 IU/L if liver metastasis is present) \[6\] Total bilirubin ≤ 1.5 mg/dL Total bilirubin \< 3.0 mg/dL for patients with Gilbert's syndrome \[7\] Creatinine ≤ 1.5 mg/dL \[8\] Any of the following criteria is met: i) Urine protein (dipstick) is negative (-) or 1+ ii) If urine protein (dipstick) is ≥ 2+; Measurement of 24-hour urine protein shows urine protein ≤ 1 g/24 hours (may be substituted by urine protein/creatinine ratio ≤ 1)
⁃ (10) Blood pressure is sufficiently controlled (systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg with ≤ 2 antihypertensive drugs \[counted as the number of combinations\]).
⁃ (11) Patients expected to survive for at least 3 months.
⁃ (12) Written consent has been obtained from the patient himself/herself after sufficient explanation of the contents of the study before registration.
⁃ (13) In the case of female patients of childbearing potential (including patients who have no menstruation for medical reasons such as chemical menopause), the patients must agree to continue to practice contraception until 5 months after the last dose of atezolizumab or 6 months after the last dose of bevacizumab, nab-PTX or PTX, whichever comes later. Patients must also agree not to breastfeed during study treatment and for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab. In the case of male patients with a partner of childbearing potential, the patient whose partner must agree to continue to practice contraception until 6 months after the last administration of PTX and nab-PTX.