A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer

Inclusion Criteria

Cycle 1:

The following inclusion criteria must be checked prior to inclusion at Cycle 1:

• Patient read, understood and signed the written informed consent before any study related activity, agreeing to participate in the study and to comply with study requirements.
• Female patient of at least 8 years of age.
• Histologically or cytologically confirmed breast cancer, including recurrent or metastatic.
• Naïve to moderately or highly emetogenic antineoplastic agents.
• Scheduled to receive at least 4 consecutive cycles of an AC combination regimen.

Notes:

• additional not emetogenic, minimally or low emetogenic antineoplastic agents are permitted at any time after start of AC combination on Day 1.
• additional highly or moderately emetogenic antineoplastic agents are only allowed on Day 1 after the start of AC combination, provided their administration is completed within 6 hours from the start of the AC combination administration.
• ECOG Performance Status of 0 or 1.
• Patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to dose of investigational product.

Notes:

• Female patients of non-childberaring potential are defined as being in post-menopausal state since at least 1 year; or having documented surgical sterilization or hysterectomy at least 3 months before study participation.
• Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence;
• Hematologic and metabolic status adequate for receiving a cycle of AC chemotherapy based on investigator's assessment.
• If the patient has a known hepatic or renal impairment, she may be enrolled in the study at the discretion of the Investigator.
• Able to read, understand, follow the study procedure and complete the patient diary.

All inclusion criteria will be checked at screening visit (Visit 1 of Cycle 1); inclusion criteria 7 will be re-checked at Day 1 (Visit 2).

Cycles 2 to 4:

The following inclusion criteria must be checked prior to inclusion at each repeated cycle:

• Participation in the study during the next cycle of chemotherapy is considered appropriate by the Investigator and does not pose unwarranted risk to the patient.
• Scheduled to receive an AC chemotherapy regimen or AC chemotherapy together with other chemotherapies as defined in Inclusion criterion #5 for Cycle 1.
• Patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to dosing of investigational product.
• Adequate hematologic and metabolic status for receiving a cycle of AC chemotherapy according to the Investigator's opinion.

All inclusion criteria will be checked at screening visit (Visit 1); inclusion criterion #3 will be re-checked at Day 1 (Visit 2).

Exclusion Criteria

Cycle 1:

The following exclusion criteria must be checked prior to inclusion at Cycle 1:

• Lactating patient.
• Current use of illicit drugs or current evidence of alcohol abuse.
• Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 and up to Day 1 of Cycle 2.
• Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5, inclusive.
• Any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day 1.
• Symptomatic primary or metastatic central nervous system (CNS) malignancy.
• Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercal