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Clinical Trial
. 2017 May 1;28(5):1036-1041.
doi: 10.1093/annonc/mdx029.

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal

P A Ott  1 , S A Piha-Paul  2 , P Munster  3 , M J Pishvaian  4 , E M J van Brummelen  5 , R B Cohen  6 , C Gomez-Roca  7 , S Ejadi  8 , M Stein  9 , E Chan  10 , M Simonelli  11 , A Morosky  12 , S Saraf  12 , K Emancipator  12 , M Koshiji  12 , J Bennouna  13
Affiliations
Clinical Trial

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal

P A Ott et al. Ann Oncol. .

Abstract

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.

Keywords: KEYNOTE-028; PD-1; PD-L1; immunotherapy; pembrolizumab; squamous cell advanced anal carcinoma.

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Figures

Figure 1.
Figure 1.
(A) Maximum change from baseline in tumor size. Includes patients with ≥1 postbaseline tumor assessment (n = 24). Responders were defined as patients having confirmed complete response or partial response per RECIST v1.1 by investigator review. (B) Longitudinal change from baseline in tumor size. Includes patients with ≥1 postbaseline tumor assessment (n = 24). Responders were defined as patients having confirmed complete response or partial response per RECIST v1.1 by investigator review. (C) Treatment exposure and response duration. The length of each bar represents the time to the last radiographic assessment. Both confirmed and unconfirmed responses per RECIST v1.1 by investigator review are shown.
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References

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