Background
Phase 2/3, open-label, randomized, multicenter RCT (China); phase 3 stage reported. N=104 HER2-positive advanced breast cancer with liver metastases (BCLM), previously treated with trastuzumab and a taxane. Disitamab vedotin (DV, RC48) is a HER2-directed ADC (MMAE payload).
Results
Interventions and follow up: Arm A: Disitamab vedotin (DV) (n=53)
Arm B: Lapatinib + capecitabine (L+C) (n=51)
Randomization: 1:1
Primary endpoint: PFS by blinded IRC (BIRC)
mFollow up: NR
Results: PFS (BIRC): 9.9 vs 4.9mo, stratified HR 0.56, 95.48% CI 0.35–0.91, P=.01 (primary endpoint met)
PFS (investigator): consistent with BIRC
Subgroups: prespecified PFS subgroups consistently favored DV
OS: NR
ORR: NR
Arm B: Lapatinib + capecitabine (L+C) (n=51)
Randomization: 1:1
Primary endpoint: PFS by blinded IRC (BIRC)
mFollow up: NR
Results: PFS (BIRC): 9.9 vs 4.9mo, stratified HR 0.56, 95.48% CI 0.35–0.91, P=.01 (primary endpoint met)
PFS (investigator): consistent with BIRC
Subgroups: prespecified PFS subgroups consistently favored DV
OS: NR
ORR: NR
Adverse events
Grade ≥3 TRAEs: 37.7% (DV) vs 36.0% (L+C)
Specific TRAEs / discontinuation: NR
Specific TRAEs / discontinuation: NR
Conclusions
DV improved BIRC-assessed PFS vs lapatinib + capecitabine (median 9.9 vs 4.9mo; HR 0.56) in trastuzumab/taxane-pretreated HER2+ BCLM, with similar grade ≥3 TRAE rates. Supports DV as an option for this poor-prognosis subgroup.
Key Limitations
Open-label; small (N=104) phase 3 stage with wide CI (upper bound 0.91). Comparator L+C is not the current global standard after trastuzumab/taxane (T-DXd, T-DM1 preferred), and no head-to-head vs T-DXd. Chinese-only population; OS not reported in the abstract. Adverse event detail limited in source abstract.
Clinical Context
Comparator-arm choice limits applicability outside regions where L+C remains a common 2L option; in guideline practice, HER2-directed ADCs (T-DXd, T-DM1) are the usual post-trastuzumab/taxane standards. DV is a HER2 ADC already carried in this database in urothelial carcinoma (RC48-C014 / HER2+ mUC). No FDA breast indication cited here; check regional regulatory status before use.
