ESMO-IO 2019 – Immunotherapy combination for loco-regionally advanced bladder cancer in the neoadjuvant setting


  • Carolina Rojido
  • Univadis
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Takeaway

  • The NABUCCO study shows checkpoint blockade with neoadjuvant immunotherapy combination is more active than in later bladder cancer disease settings and improves pathological complete responses (pCRs).

Why this matters

  • 30-40% of patients are not eligible for neoadjuvant cisplatin which significantly worsens their outcomes.
  • Previous neoadjuvant studies like ABACUS (atezolizumab monotherapy) and PURE-01 (pembrolizumab monotherapy) resulted in pCRs of 31% and 42%.

Key results

  • Feasibility:
    • 23 patients (96%) had resection within 12 weeks of first infusion.
    • 1 patient had a 4-week delay because of immune-related adverse event (haemolysis).
  • Safety:
    • 55% had grade 3-4 immune-related toxicities.
    • 30-day mortality after surgery was 0%.
    • 90-day mortality: 1 due to rapidly progressive metastatic disease.
  • Efficacy:
    • Overall pCR was 46%.

Study design

  • A phase 1b study, NABUCCO, included 24, high-risk, stage III urothelial bladder cancer patients ineligible or having refused cisplatin.
  • They received ipilimumab 3 mg/kg the first week, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg the 4th week, and ipilimumab 3 mg/kg the seventh week.
  • CT-scans were done at baseline and at week 7.
  • Surgery was done between weeks 9 and 11.

Limitations

  • Very early, small study.
  • Randomised trials in the perioperative setting are ongoing.

Expert commentary

“Only chemotherapy is approved for neoadjuvant treatment but there are a lot of trials ongoing in many countries for cisplatin eligible and ineligible patients so oncologists can consider these options with their patients.” said Dr M Van der Heijden, Netherlands Cancer Institute, Amsterdam, Netherlands.