PURE-01 now, PURE-01 later.
The Study: That’s because chemo improves survival by an absolute rate of 5% and results in a pathologic complete response (pCR) in as many as a third of patients. The problem is that a lot of patients don’t get neoadjuvant chemo, in large part due to platinum intolerance and the comorbidities that often go along with bladder cancer. Now that immunotherapy is an established platinum alternative for metastatic MIBC, it’s time to see how it fares in the neoadjuvant setting. PURE-01 was a phase 2 trial of neoadjuvant pembrolizumab x 3 cycles in 50 patients planning to undergo radical cystectomy for MIBC. At the time surgery, 42% had a pCR while over half were down-staged to no longer muscle-invasive. As expected, patients with higher PD-L1 expression and higher tumor mutational burden got the biggest benefit. Which is good considering 70% of enrollees had >10% PD-L1 expression. For tumor mutational burden, ≥15 mutations per mega-base was most associated with pCR.
Bottom Line: Most muscle invasive bladder cancers express PD-L1, which is associated with a >50% pCR rate at radical cystectomy following neoadjuvant pembrolizumab. | Necchi, J Clin Oncol 2018