Necchi A, et al. - Researchers aimed at assessing the activity of pembrolizumab as neoadjuvant immunotherapy prior to radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Neoadjuvant pembrolizumab resulted in a pathologic complete response (pT0) in 42% of patients and it was safely administered. Hence, for the treatment of MIBC, and when limited to patients with programmed death-ligand 1 (PD-L1)–positive or high-tumor mutation burden (TMB) tumors, pembrolizumab seems to be a valuable neoadjuvant therapy.

Methods

• Patients with a predominant urothelial carcinoma histology and clinical (c)T≤3bN0 stage tumor were included in the PURE-01 study.
• Three cycles of pembrolizumab 200 mg every 3 weeks were administered before RC.
• pT0 was the primary end point in the intention-to-treat population.
• Researchers performed biomarker analyses including PD-L1 expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay.

Results

• From February 2017 to March 2018, researchers enrolled 50 patients.
• cT3 tumor, cT2 tumor and cT2-3N1 tumor were noted in 27 patients (54%), 21 patients (42%), and two patients (4%), respectively.
• A grade 3 transaminase increase was observed in 1 patient (2%) leading to discontinuation of pembrolizumab.
• RC was performed on all patients; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%).
• Twenty-seven patients achieved downstaging to pT<2 as a secondary end point (54%; 95% CI, 39.3% to 68.2%).
• RC indicated pT0 in 54.3% of patients with PD-L1 CPS ≥ 10% (n = 35), whereas RC indicated pT0 in only 13.3% of those with CPS < 10% (n = 15).
• They observed a significant nonlinear correlation between TMB and pT0, with a cutoff at 15 mutations/Mb.
• pT0 and non-pT0 cohorts showed significantly different expression of several genes in pretherapy lesions.
• Residual tumors showed significant post-therapy changes in the TMB and evidence of adaptive mechanisms of immune resistance.