Among patients with previously treated advanced anal squamous cell carcinoma, pembrolizumab monotherapy was associated with durable responses in antitumor activity and improved overall survival, according to a study in the Lancet Gastroenterology & Hepatology.

Investigators reported efficacy and safety results from the phase 2 KEYNOTE-158 study, an international, open-label, nonrandomized trial conducted at 38 centers. Eligible patients were aged ≥18 years and had histologically or cytologically confirmed unresectable or metastatic disease, previous failure of or intolerance to standard therapy or no standard therapy options, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, life expectancy of ≥3 months, and adequate organ function.

The participants received pembrolizumab 200 mg intravenously on day 1 of every 3-week cycle for 2 years or until confirmed disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint was objective response, which was the proportion of patients who had a complete or partial response.

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A total of 112 patients (median age, 61 years; IQR, 53-67 years) were enrolled from March 3, 2016, to July 23, 2018. Of the cohort, 91 (81%) were women, 104 (93%) had M1 disease, and 75 (67%) had PD-L1-positive tumors. The median time from first dose to data cutoff on June 27, 2019, was 34.7 months (IQR, 32.5-36.4 months).

After the follow-up, 12 patients (11%; 95% CI, 6-18) had an objective response based on RECIST 1.1 criteria, including 6 (5%) patients who had a complete response and 6 (5%) who had a partial response. Objective responses were observed in 11 (15%; 95% CI, 8-25) of 75 patients in the PD-L1-positive group and 1 (3%; 95% CI, 0-17) of 30 patients in the PD-L1-negative group.

Participants’ median progression-free survival (PFS) was 2.0 months (95% CI, 2.0-2.1), the 12-month PFS was estimated to be 15% (95% CI, 9-22), and the 24-month PFS was estimated to be 9% (95% CI, 4-15).

Treatment-related adverse events (TRAEs) occurred in 68 (61%) patients, with fatigue (17 patients [15%]), diarrhea (13 patients [12%]), hypothyroidism (13 patients [12%]), and nausea (13 patients [12%]) the most commonly occurring of any grade. Serious TRAEs were reported in 12 (11%) patients. Additionally, 25 (22%) patients had at least 1 immune-mediated adverse event, and 5 patients (4%) had grade 3 immune-mediated adverse events.

Among several study limitations, tumor-specific characteristics for individual tumor cohorts were not obtained, and so information regarding human papillomavirus infection was not available. Additionally, further research on anal squamous cell carcinoma tumors may help to better characterize the biological features that are associated with pembrolizumab efficacy in this patient group.

“Our findings provide much-needed clinical evidence with an anti-PD-1 monoclonal antibody in a large group of patients with previously treated advanced anal squamous cell carcinoma,” concluded the researchers. “On the basis of our analysis, 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.”

Disclosure: This study was funded by Merck Sharp & Dohme. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Marabelle A, Cassier PA, Fakih M, et al. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Lancet Gastroenterol Hepatol. Published online January 31, 2022. doi: 10.1016/S2468-1253(21)00382-4