TROPiCS-02

Design, population and eligibility

Treatment and comparator

Sacituzumab govitecan 10 mg/kg IV on days 1 and 8 every 21 days versus physician's-choice single-agent chemotherapy (eribulin, capecitabine, gemcitabine or vinorelbine) until progression or unacceptable toxicity.

Primary and secondary endpoints

Primary endpoint: PFS by blinded independent central review (RECIST 1.1). Key secondary endpoint: OS. Other endpoints included response, duration of response, safety and patient-reported QoL.

Key efficacy results

Median PFS by BICR was 5.5 versus 4.0 months; HR 0.66 (95% CI 0.53–0.83; p=0.0003). At final exploratory analysis, median PFS remained 5.5 versus 4.0 months; HR 0.65 (95% CI 0.53–0.81; p=0.0001).

Median OS was 14.4 versus 11.2 months; HR 0.79 (95% CI 0.65–0.96; p=0.020). ORR was 21% versus 14%; median duration of response 8.1 versus 5.6 months. Time to deterioration in global health status/QoL was 4.3 versus 3.0 months; HR 0.75 (95% CI 0.61–0.92; p=0.0059).

Source-reported outcome visualization

Fixed-time PFS estimates at final analysis.

Kaplan–Meier estimates at 6 and 12 months. The 6-month absolute difference is 16.2 percentage points.

Absolute effect

At 6 months, PFS was 45.6% versus 29.4%, an absolute difference of 16.2 percentage points; approximate landmark NNT 7 at 6 months for one additional patient progression-free. At 12 months, PFS was 21.7% versus 8.4%, a 13.3-point difference; approximate NNT 8. These are fixed-time PFS estimates, not median-survival-derived NNTs.

Trial-specific toxicity and treatment burden

Grade ≥3 treatment-emergent adverse events occurred in 74% versus 60%. Grade ≥3 neutropenia occurred in 51% versus 39%; grade ≥3 diarrhoea in 10% versus 1%. One treatment-related death (septic shock from neutropenic colitis) occurred with sacituzumab govitecan. Adverse events led to treatment discontinuation in approximately 6% versus 4%.

Primary supportive-care issues include neutropenia, diarrhoea, anaemia, nausea and alopecia. G-CSF and antidiarrhoeal management may be needed according to risk and symptoms.

Quality of life and patient-reported outcomes

Time to deterioration in global health status/QoL favoured sacituzumab govitecan (median 4.3 versus 3.0 months; HR 0.75; p=0.0059), as did time to deterioration in fatigue (2.2 versus 1.4 months; HR 0.73; p=0.0021).

Subgroups and applicability

OS benefit was consistent across Trop-2 expression subgroups and clinically relevant subgroups. The study population was heavily pretreated, with most patients having visceral metastases and prior CDK4/6 inhibitor exposure.

Current-practice context · reviewed 2 November 2026

Sacituzumab govitecan is an evidence-based option after endocrine therapy, CDK4/6 inhibition and chemotherapy in HR-positive/HER2-negative metastatic breast cancer. Treatment sequencing should consider prior ADC exposure, current approvals and newer endocrine-targeted options; TROPiCS-02 directly addresses a heavily pretreated population.

Limitations and critical interpretation

The comparator was physician's-choice single-agent chemotherapy, not another ADC. Median follow-up was relatively short for OS. Patients had substantial prior therapy; results should not be extrapolated to earlier-line disease. Treatment-related toxicity and QoL need active monitoring.

Bottom line: TROPiCS-02 demonstrates statistically significant PFS and OS benefit for sacituzumab govitecan over single-agent chemotherapy in heavily pretreated HR-positive/HER2-negative disease, with more grade ≥3 toxicity but delayed QoL deterioration.

Primary sources and follow-up publications

1. TROPiCS-02 final OS analysis, Lancet 2023
2. TROPiCS-02 primary PFS report, JCO 2022
3. FDA clinical review and efficacy tables
4. TROPiCS-02 registry

All outcome values above are transcribed from the linked trial reports or their prespecified follow-up publications. Unreported values are not imputed. No NNT is derived from median survival.