- 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.
- 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.
- 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.
- Small size for biomarker evaluation.