Oral capecitabine plus trastuzumab versus paclitaxel plus trastuzumab for small HER2‑positive, node‑negative breast cancers as adjuvant treatment.

A Randomized, Open-label, Multi-center Phase III Study Comparing the Efficacy of Oral Chemotherapy Combined With Trastuzumab Versus Paclitaxel Combined With Trastuzumab in the Adjuvant Treatment of HER2-positive, Lymph Node-negative Early Breast Cancer Patients(ORCHID-PLUS)

This trial tests whether giving oral capecitabine with trastuzumab instead of paclitaxel with trastuzumab can prevent recurrence in women with small (≤2 cm), HER2‑positive, node‑negative breast cancer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 2306 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy, trastuzumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06992882 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label phase III study enrolling women with surgically resected, stage IA (pT1mic–T1cN0M0) HER2‑positive breast cancer. Participants are randomized to receive trastuzumab combined with either an oral chemotherapy (capecitabine) or paclitaxel and are followed for treatment effectiveness and safety. Key eligibility includes age 18–70, tumor ≤2 cm, node‑negative status, confirmed HER2 overexpression or amplification, and adequate organ and cardiac function, with randomization within 8 weeks of surgery. The trial compares clinical outcomes and adverse effects between the two adjuvant regimens to identify a less toxic, effective option for this low‑risk group.

Who should consider this trial

Good fit: Women aged 18–70 with completely resected, HER2‑positive, node‑negative early breast cancer (tumor ≤2 cm, pT1mic–T1cN0M0) who have normal organ and cardiac function and can be randomized within 8 weeks after surgery are ideal candidates.

Not a fit: Patients with larger tumors, node‑positive or metastatic disease, HER2‑negative tumors, significant organ or cardiac dysfunction, or those unable to receive treatment at the study site are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could offer an effective adjuvant option that uses an oral drug and may reduce some toxicities compared with current paclitaxel‑based regimens.

How similar studies have performed: Prior trials such as the APT trial established paclitaxel plus trastuzumab as an effective adjuvant approach for small node‑negative HER2‑positive cancers, while capecitabine plus trastuzumab in the adjuvant early‑stage setting remains less studied and relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Females aged 18\~70;
2. The postoperative pathological stage of early breast cancer is stage IA: the longest diameter of invasive cancer is not more than 2cm and the lymph node is negative: pT1mic-T1cN0M0 (micro-invasion needs to meet multiple foci).
3. Pathological immunohistochemistry must meet the following conditions: HER-2 (3) or HER-2 (0-2) but amplified by FISH or CISH testing.
4. The maximum number of weeks (56 days) from surgery to randomization is not more than 8 weeks (56 days).
5. The function of major organs is normal, that is, the following criteria are met: (1) The criteria for routine blood examination must meet: HB ≥90 g/L (no blood transfusion within 14 days); ANC ≥1.5×109 /L； PLT ≥100×109 /L； (2) Biochemical tests must meet the following standards: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance \>50 ml/min (Cockcroft-Gault formula);
6. Cardiac function: ECG was generally normal, QTc \< 470 ms, LVEF \>50%;
7. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up

Exclusion Criteria:

1. Patients who have received neoadjuvant therapy, including chemotherapy, targeted, radiotherapy, or endocrine therapy;
2. History of other malignant tumors in the past, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
3. metastasis of any site;
4. Pregnant or lactating women, women of childbearing age who cannot use effective contraception;
5. Patients who are also participating in other clinical trials;
6. Severe organ function (heart, lung, liver, kidney) insufficiency, LEVF \< 50% (ultrasound), severe cardiovascular and cerebrovascular diseases (such as: unstable angina, chronic heart failure, uncontrolled hypertension \>150/90mmgh, myocardial infarction or cerebrovascular accident) within 6 months before enrollment; Diabetic patients with poor glycemic control; Patients with severe hypertension;
7. Severe or uncontrolled infection;
8. Those who have a history of psychotropic drug abuse and cannot be quit or have a history of mental disorder;
9. Patients who are judged by the investigator to be unsuitable to participate in this study.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center Shanghai, China, 200032 — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Zhimin Shao, MD

Conditions: HER2-positive Breast Cancer