Adjuvant bacillus Calmette-Guérin (BCG) immunotherapy versus BCG combined with disitamab vedotin in BCG-naïve high-risk non-muscle invasive bladder cancer with HER2 expression: A real-world study.

OBJECTIVE

Recurrence is not rare for high-risk non-muscle invasive bladder cancer (HR-NMIBC) after bacillus Calmette-Guérin (BCG) immunotherapy. We aimed to introduce disitamab vedotin (DV) to BCG and evaluate its efficacy.

METHODS

Consecutive BCG-naïve patients with HER2-expressing HR-NMIBC receiving transurethral resection followed by BCG alone or combined with intravenous DV (BCG + DV) were enrolled in this retrospective study. Relationship with recurrence-free survival (RFS) was analyzed using log-rank and Cox regression analyses. Given the differences in baseline patient characteristics, propensity score matching (PSM) was also implemented to address the heterogeneity.

RESULTS

A total of 117 patients with a median follow-up of 19 months were finally evaluated (BCG: 85, BCG + DV: 32). Compared with BCG group, BCG + DV group had significantly higher proportions of multifocal lesions (81.2%/57.6%), HER2 2+/3+ tumors (87.6%/51.8%), very-high-risk (VHR) disease (31.3%/14.1%) and tumor residue after initial resection (40.6%/21.2%). The 3-month complete response rates of BCG + DV and BCG groups were 100% and 91.8%, respectively (p = 0.187). BCG + DV yielded superior RFS (1-year: 92.3%, 2-year: 86.5%) versus BCG (1-year: 80.0%, 2-year: 64.6%; p = 0.041), and this advantage was pronounced in HER2 2+/3+, VHR and residual disease subgroups. Independent risk factors of recurrence after BCG monotherapy included large tumor, HER2 2+/3+ and residual disease. Combination treatment emerged as the strongest predictor of improved RFS for the entire cohort. After PSM, BCG + DV still rendered significantly better RFS in both entire matched cohort and aforementioned subgroups.

CONCLUSION

Addition of DV to BCG provided favorable early response and superior intermediate-term RFS for BCG-naïve HER2-expressing HR-NMIBC, highlighting its prospect in HR-NMIBC management.