This clinical trial is a prospective, observational, multicenter cohort study evaluating the efficacy and safety of NEPA (netupitant/palonosetron) in patients with HER2-positive or HER2-low advanced breast cancer treated with T-DXd

The observation period of this study is until the discontinuation after administration of T-Dxd or until 8 Cycle.

• Acute phase: 0 -24 hours after T-DXd administration
• Delayed phase: >24-120 hours after T-DXd administration
• Overall phase: 0-120 hours after T-DXd administration
• Long-delayed phase: >120-504 hours
• Extended overall phase: 0-504 hours

Primary objectives: to evaluate the efficacy and safety of NEPA for CINV prevention in advanced breast cancer patients receiving at least 2 cycles of T-DXd across all defined assessment periods (acute, delayed, overall, long-delayed, and extended overall phases).

Inclusion Criteria:

1. Age >19 years

2. Histologically confirmed breast cancer with metastatic or locally advanced breast cancer not amenable to definitive surgery, with or without measurable disease

3. Stage IV breast cancer at initial diagnosis (de novo) or progression at distant metastatic sites following curative surgery

4. HER2-positive breast cancer (HER2 IHC 3+ or IHC 2+/ISH-positive) or HER2-low breast cancer (HER2 IHC 2+/ISH-negative or HER2 IHC 1+), as defined by the ASCO/CAP guidelines

5. ECOG performance status 0-2

6. Patients who are scheduled to initiate their first cycle of T-DXd therapy

7. Patients who are scheduled to receive netupitant/palonosetron (NEPA) for the prevention of acute and delayed CINV according to the approved indications and dosage instructions

8. Patients who agree to use highly effective contraception methods or not of childbearing potential. Highly effective contraception methods include:

   A. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

   B. Total hysterectomy (surgical removal of the uterus and cervix) or tubal ligation (getting your "tubes tied") at least six weeks before taking study treatment.

   C. Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.

   D. Combination of the following:

   I. Placement of an intrauterine device (IUD) or intrauterine system (IUS) II. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

9. Written informed consent

Exclusion Criteria:

1. Patients who experienced nausea and/or vomiting within 7 days prior to the first cycle of T-DXd treatment
2. Leptomeningeal metastasis and/or brain metastasis
3. Patients with hypersensitivity to any components of the drug or 5-HT3 receptor antagonists.
4. Pregnant women or those suspected of being pregnant, as well as breastfeeding mothers.
5. Any illness or condition that, in the opinion of the Investigator, may pose unwarranted risks in administering T-DXd or NEPA to the patient.
6. Patients requiring treatment with steroids, antiemetics, benzodiazepines, antipsychotics, or other contraindicated drugs, including but not limited to pimozide, terfenadine, astemizole, cisapride, rifampin, carbamazepine, phenytoin, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, fluvoxamine, SSRIs, SNRIs, ritonavir, or nelfinavir.

Patients who had not been previously treated with T-DXd and are scheduled to receive their first cycle of T-DXd with NEPA

It will be decided later.