TY - JOUR
T1 - Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal
AU - Ott, P. A.
AU - Piha-Paul, S. A.
AU - Munster, P.
AU - Pishvaian, M. J.
AU - van Brummelen, E. M.J.
AU - Cohen, R. B.
AU - Gomez-Roca, C.
AU - Ejadi, S.
AU - Stein, M.
AU - Chan, E.
AU - Simonelli, M.
AU - Morosky, A.
AU - Saraf, S.
AU - Emancipator, K.
AU - Koshiji, M.
AU - Bennouna, J.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Background: Safety and efficacy of pembrolizumab, a humanized programmed death 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 anal carcinoma.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 endpoints were safety and overall response rate per investigator review. Secondary endpoints included progression-free survival, overall survival, and response duration. Data cutoff date was 1 July 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 histology, four had confirmed partial response, for an overall response rate of 17% [95% confidence interval (CI), 5%-37%) and 10 (42%) had confirmed stable disease, for a disease control rate of 58%. One additional patient with non-squamous histology had confirmed stable disease.Conclusion: In this population of patients with PD-L1-positive advanced squamous cell anal carcinoma, pembrolizumab demonstrated a manageable safety profile and encouraging antitumor activity. These data support further study of pembrolizumab for this patient population.ClinicalTrials.gov: NCT02054806.
AB - Background: Safety and efficacy of pembrolizumab, a humanized programmed death 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 anal carcinoma.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 endpoints were safety and overall response rate per investigator review. Secondary endpoints included progression-free survival, overall survival, and response duration. Data cutoff date was 1 July 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 histology, four had confirmed partial response, for an overall response rate of 17% [95% confidence interval (CI), 5%-37%) and 10 (42%) had confirmed stable disease, for a disease control rate of 58%. One additional patient with non-squamous histology had confirmed stable disease.Conclusion: In this population of patients with PD-L1-positive advanced squamous cell anal carcinoma, pembrolizumab demonstrated a manageable safety profile and encouraging antitumor activity. These data support further study of pembrolizumab for this patient population.ClinicalTrials.gov: NCT02054806.
KW - KEYNOTE-028
KW - PD-1
KW - PD-L1
KW - immunotherapy
KW - pembrolizumab
KW - squamous cell advanced anal carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85026837838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026837838&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdx029
DO - 10.1093/annonc/mdx029
M3 - Article
C2 - 28453692
AN - SCOPUS:85026837838
SN - 0923-7534
VL - 28
SP - 1036
EP - 1041
JO - Annals of oncology : official journal of the European Society for Medical Oncology
JF - Annals of oncology : official journal of the European Society for Medical Oncology
IS - 5
ER -