MIBC: RNA-based biomarkers for neoadjuvant pembrolizumab

  • Necchi A & al.
  • Eur Urol
  • 9 Mar 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Higher RNA-based immune signature scores showed significant association with complete response in patients with muscle invasive bladder cancer (MIBC) receiving neoadjuvant pembrolizumab, but not after neoadjuvant chemotherapy.
  • No significant PFS improvement was observed with either treatment.

Why this matters

  • RNA profiling can help identify patients likely to benefit from preoperative immunotherapy.

Study design

  • Molecular expression was evaluated in participants from the prospective PURE-01 study (n=84; treatment, neoadjuvant pembrolizumab) and a retrospective multicenter cohort (n=140; treatment, neoadjuvant chemotherapy).
  • Median follow-up was 18.4 and 8 months, respectively.
  • Funding: MSD.

Key results

  • 4 immune signatures showed a significant association (aORs) with complete response in the PURE-01 study, but not in the retrospective cohort:
    • The Immune190: 1.51 (P=.02).
    • Interferon alpha: 1.07 (P=.006).
    • Interferon gamma: 1.11 (P=.004).
    • Inflammatory: 1.23 (P=.01).
  • No significant difference in PFS was observed with higher vs lower Immune190 scores in the PURE-01 (P=.15) and retrospective cohorts (P=.10).
  • Basal subtypes (across classifications) with higher vs lower Immune190 scores showed superior PFS after pembrolizumab therapy (all P=.04).
  • Neuroendocrine-like tumors had the worst 2-year PFS:
    • PURE-01: 33%.
    • Retrospective cohort: 0%.
  • Claudin-low tumors had the best PFS with pembrolizumab vs chemotherapy.

Limitations

  • Short follow-up.