What is the role of adjuvant capecitabine (Xeloda) in a patient with cT2N0 triple-negative breast cancer who did not achieve a pathological complete response after neoadjuvant chemotherapy?

Adjuvant Capecitabine for cT2N0 Triple-Negative Breast Cancer with Residual Disease After Neoadjuvant Chemotherapy

Yes, you should offer adjuvant capecitabine (6-8 cycles) to this patient with triple-negative breast cancer who has residual invasive disease after completing standard neoadjuvant anthracycline- and taxane-based chemotherapy. 1

Evidence-Based Recommendation

Primary Guideline Support

Multiple major oncology societies explicitly recommend adjuvant capecitabine in this exact clinical scenario:

• ASCO (2018) states that patients with early-stage, HER2-negative breast cancer with pathologic invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to 6-8 cycles of adjuvant capecitabine, with preferential support for hormone receptor-negative (triple-negative) disease. 1

• ESMO (2019) recommends that after delivery of standard 4-8 cycles of anthracyclines and taxanes, in the absence of pathological complete response, addition of 6-8 cycles of capecitabine resulted in improvement of disease-free survival and overall survival, particularly in triple-negative tumors, and this option may be offered to triple-negative patients who do not achieve pCR after optimal neoadjuvant chemotherapy. 1

• ESO-ESMO (2020) confirms that for patients with triple-negative disease not achieving pCR after standard preoperative regimens, addition of 6-8 cycles of capecitabine may be considered. 1

Supporting Evidence from CREATE-X Trial

The recommendation is based primarily on the CREATE-X phase III trial, which demonstrated:

• Disease-free survival improvement: 74.1% versus 67.6% at 5 years (HR 0.70; 95% CI 0.53-0.92; p=0.01), representing an absolute benefit of 6.5%. 2

• Overall survival improvement: 89.2% versus 83.6% (HR 0.59; 95% CI 0.39-0.90; p=0.01), representing an absolute benefit of 5.6%. 2

• Triple-negative subgroup showed even greater benefit: DFS 69.8% versus 56.1% (HR 0.58; 95% CI 0.39-0.87) and OS 78.8% versus 70.3% (HR 0.52; 95% CI 0.30-0.90). 1, 2

Real-World Confirmation

Recent real-world data from three comprehensive cancer centers (2025) involving 661 patients with residual disease after neoadjuvant chemotherapy confirmed that adjuvant capecitabine was associated with significantly improved recurrence-free survival (HR 0.70; 95% CI 0.54-0.91; P=0.008), distant recurrence-free survival (HR 0.71; 95% CI 0.54-0.93; P=0.01), and overall survival (HR 0.66; 95% CI 0.49-0.90; P=0.009). 3

Dosing and Administration

Standard dosing: Capecitabine 1,250 mg/m² orally twice daily on days 1-14 of each 21-day cycle for 6-8 cycles. 1

Critical Age-Related Dosing Consideration

For patients ≥65 years old, start at a reduced dose of 1,000 mg/m² twice daily without escalation. The standard 1,250 mg/m² dose was associated with 34% rate of grade 3 or higher toxicity in older patients, including two treatment-related deaths in a North American trial. 1, 4

Toxicity Management

Expected Adverse Events

• Hand-foot syndrome: Most frequent adverse event, occurring in 73.4% of patients (11.1% grade 3). 1, 4
• Diarrhea: Common, particularly requiring proactive management. 4
• Hematologic toxicity: Monitor for thrombocytopenia. 4

Monitoring and Dose Modifications

• Close monitoring is essential, particularly in the first cycles. 4
• Patients with renal insufficiency require dose adjustment since elimination is primarily renal. 4
• Grade 3-4 toxicity may require dose reduction or treatment interruption. 4

Important Clinical Caveats

Unknown Interactions

The value of adjuvant capecitabine after the use of a platinum compound in the neoadjuvant setting is currently unknown. 1 If your patient received carboplatin during neoadjuvant therapy, the evidence base is less robust, though capecitabine remains a reasonable option given the high-risk nature of residual triple-negative disease.

Real-World Tolerability Concerns

While guidelines strongly support this approach, real-world US data suggest tolerability challenges:

• Only 34.8% of US patients completed treatment as prescribed in one series, compared to better completion rates in the Asian CREATE-X population. 5
• 69.6% experienced hand-foot syndrome and 13% required hospitalization for side effects in US cohorts. 5
• Some real-world studies failed to demonstrate survival benefit, possibly due to poor treatment completion rates. 6, 7

Clinical implication: Aggressive supportive care, patient education about expected toxicities, and close monitoring are essential to maximize treatment completion and benefit.

Patient Selection Considerations

The evidence quality is rated as intermediate with a moderate strength of recommendation by ASCO. 1 However, given that:

• Your patient has triple-negative disease (the subgroup with strongest benefit)
• Residual disease after neoadjuvant therapy confers high recurrence risk
• The absolute survival benefit is clinically meaningful (5-6%)
• This is the only evidence-based adjuvant escalation strategy available

The benefit-to-risk ratio strongly favors treatment in this clinical scenario.

Contraindications to Consider

Do not use capecitabine if:

• Age ≥75 years (excluded from CREATE-X trial) 1
• Creatinine clearance <50 mL/min (majority excluded from trial) 1
• Known DPD deficiency (3-5% of population at risk for life-threatening toxicity) 4