Metastatic bladder cancer: add-on acalabrutinib fails to improve response

  • Zhang T & al.
  • Cancer
  • 5 Aug 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Adding acalabrutinib to pembrolizumab does not improve clinical outcomes in patients with platinum-refractory metastatic urothelial cancer vs pembrolizumab monotherapy.
  • Combination was associated with increased toxicity.

Why this matters

  • Pembrolizumab has shown a response rate of approximately 20% in clinical trials in this setting.
  • Further studies to evaluate real-time biomarkers for treatment response are warranted.

Study design

  • Randomized phase 2 RAPID CHECK trial.
  • 75 patients with platinum-refractory metastatic urothelial cancer were randomly assigned to pembrolizumab with or without acalabrutinib.
  • Funding: Acerta Pharma.

Key results

  • The overall response rate was 25.7% with pembrolizumab (complete response [CR], 8.6%) and 20% with pembrolizumab+acalabrutinib (CR, 10%).
  • Grade 3/4 adverse event (AE) rate was 54.3% in the pembrolizumab group and 75.0% in the pembrolizumab+acalabrutinib group.
  • The most frequent grade 3/4 pembrolizumab-related AEs in the pembrolizumab and acalabrutinib group were increased alanine aminotransferase, increased aspartate aminotransferase, and maculopapular rash.
  • The most frequent grade 3/4 acalabrutinib-related AEs in the pembrolizumab and acalabrutinib cohort were fatigue, anemia, diarrhea, decreased platelet count, and dyspnea.
  • Toxicity-related discontinuation rate was 22.9% in the pembrolizumab and 40.0% in the pembrolizumab and acalabrutinib group.
  • Overall myeloid-derived suppressor cell levels were not correlated with a clinical response.

Limitations

  • Small size for biomarker evaluation.