Colon to Rectum

Lancet Gastroenterol Hepatol. 2022;7(5):446–54

Marabelle A, Cassier PA, Fakih M, Kao S, Nielsen D, Italiano A, Guren TK, van Dongen MGJ, Spencer K, Mendonca Bariani G, Ascierto PA, Santoro A, Shah M, Asselah J, Iqbal S, Takahashi S, Piha-Paul SA, Ott PA, Chatterjee A, Jin F, Norwood K, Delord JP

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: Results from the non-randomized, multicohort, multicenter, phase 2 KEYNOTE-158 study

Background: Outcomes in advanced anal squamous cell carcinoma (SCC) are poor, with few treatment options and controlled clinical trials. The authors evaluated the efficacy and safety of pembrolizumab in patients with advanced anal SCC (cohort A) from the phase 2 KEYNOTE-158 study.
Methods: Eligible patients enrolled in the ongoing non-randomized, multicohort, multicenter, phase 2 KEYNOTE-158 study, which was done across 38 centers worldwide, were aged ≥ 18 years; had histologically or cytologically confirmed advanced or metastatic anal SCC; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a programmed cell death-ligand 1 (PD-L1)-evaluable tissue sample. Patients received pembrolizumab 200 mg intravenously every 3 weeks for 2 years, or until disease progression, unacceptable toxicity, investigator’s decision to withdraw the patient from the study, or withdrawal of patient consent. The primary end point was objective response, as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Efficacy and safety analyses included all patients who received at least 1 dose of pembrolizumab.
Findings: Between March 3, 2016, and July 23, 2018, 163 patients were screened, of whom 112 were enrolled and treated in the anal cancer cohort. 91 (81%) patients were female, 104 (93%) had M1 disease, and 75 (67%) had PD-L1-positive tumors. The median time from first dose to data cut-off (June 27, 2019) was 34.7 (interquartile range, 32.5–36.4) months. 12 (11%; 95% confidence interval [CI]: 6–18) patients had an objective response, including 11 (15%; 95% CI: 8–25) of 75 patients with PD-L1-positive tumors and 1 (3%; 95% CI: 0–17) of 30 patients with PD-L1-negative tumors. 68 (61%) patients had treatment-related adverse events (20 [18%] patients had grade 3–4 adverse events), the most common of which were fatigue (17 patients), diarrhea (13), hypothyroidism (13), and nausea (13). Serious treatment-related adverse events occurred in 12 (11%) patients. 25 (22%) patients had immune-mediated adverse events, and 1 (1%) had an infusion reaction. There were no treatment-related deaths.

Interpretation: Pembrolizumab monotherapy is a possible treatment option with a favorable benefit-risk ratio for patients with previously treated advanced anal squamous cell carcinoma who have no alternative satisfactory treatment options.

Dr. A. Marabelle, Gustave Roussy, INSERM U1015, Université Paris Saclay, Villejuif, France,

DOI: DOI: 10.1016/s2468-1253(21)00382-4

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