Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal
Mené sur 43 patients atteints d'un carcinome du canal anal de stade avancé exprimant PD-L1, cet essai de phase Ib évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité du pembrolizumab, un anticorps monoclonal ciblant le récepteur PD-1
Background: Safety and efficacy of pembrolizumab, a humanized programmed death 1 (PD-1) monoclonal antibody, was assessed in KEYNOTE-028, a multicohort, phase Ib trial for patients with programmed death ligand 1 (PD-L1)–positive advanced solid tumors. We report results for the cohort of patients with advanced carcinoma of the anal canal. Patients and methods: Patients with PD-L1–positive tumors (≥1%) received intravenous pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter per Response Evaluation Criteria In Solid Tumors, version 1.1. Primary end points were safety and overall response rate (ORR) per investigator review. Secondary end points included progression-free survival, overall survival, and response duration. Data cutoff date was July 1, 2015. Results: Of the 43 patients with advanced anal carcinoma evaluable for PD-L1 expression, 32 (74%) had PD-L1–positive tumors as assessed with the 22C3 prototype assay, of whom 25 were enrolled between April and September 2014. Sixteen patients (64%) experienced treatment-related adverse events; the most common ones were diarrhea and fatigue in four patients (16%) each and nausea in three patients (12%). There were no treatment-related deaths or discontinuations as of the data cutoff date. Among the 24 patients with squamous cell carcinoma (SCC) histology, four had confirmed partial response, resulting in an ORR of 17% (95% confidence interval [CI], 5-37%) and 10 (42%) had confirmed stable disease, resulting in a disease control rate of 58%. One additional patient with nonsquamous histology had confirmed stable disease. Conclusion: In this population of patients with PD-L1–positive advanced SCC anal carcinoma, pembrolizumab demonstrated a manageable safety profile and encouraging antitumor activity. These data support further study of pembrolizumab for this patient population.