Journal: NPJ precision oncology
This multicenter retrospective real-world study evaluated neoadjuvant disitamab vedotin (RC48), a HER2-directed antibody–drug conjugate, combined with PD‑1 inhibitors in localized muscle-invasive bladder cancer, particularly addressing the unmet need in cisplatin-ineligible or relapsed patients.
Design and treatment:
- Population: 25 patients with localized MIBC (cT2–4aN0–2M0) who proceeded to radical cystectomy.
- Regimen: At least 4 cycles of RC48 (2.0 mg/kg every 2 or 3 weeks) plus a PD‑1 inhibitor (toripalimab, tislelizumab, or pembrolizumab) as neoadjuvant therapy.
Efficacy:
- Pathologic complete response (pCR): 48%.
- Pathologic downstaging (any reduction in T/N stage): 88%.
- With a median follow-up of 17.0 months:
- 12‑month disease-free survival: 91.5%.
- 12‑month overall survival: 100%.
Biomarkers and prognostic factors:
- HER2 overexpression (IHC 3+) was significantly associated with higher response: Odds ratio (OR) 6.75; 95% CI 1.16–39.20; p = 0.033.
- More advanced clinical stage (>T2N0M0) predicted poorer response: OR 0.15; 95% CI 0.03–0.86; p = 0.033.
Safety:
- Treatment-related adverse events were reported as manageable; no new safety signals were highlighted.
Implications:
- RC48 plus PD‑1 blockade shows high pCR and downstaging rates with encouraging short-term DFS and OS in localized MIBC.
- HER2 IHC 3+ appears to be a relevant predictive biomarker.
- These results support further prospective validation, ideally in biomarker-selected cohorts and with longer follow-up to define durability and survival benefit versus current cisplatin-based and immunotherapy-based standards.