Pembrolizumab monotherapy demonstrated a favorable benefit-risk ratio in patients with previously treated, advanced anal squamous cell carcinoma, according to researchers.

These results, from the phase 2 KEYNOTE-158 trial, were published in The Lancet Gastroenterology & Hepatology.

KEYNOTE-158 is a multicohort trial (ClinicalTrials.gov Identifier: NCT02628067) enrolling patients with rare advanced solid tumors. Cohort A enrolled 112 patients with advanced, previously treated anal squamous cell carcinoma.


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Most patients in cohort A were women (81%), had M1 disease (93%), had received at least 2 prior lines of therapy (74%), and had PD-L1-positive tumors (67%). The patients’ median age was 61 years (interquartile range, 53-67 years). 

All patients received pembrolizumab at 200 mg intravenously every 3 weeks for 2 years or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR).

The median follow-up was 34.7 months. At the data cutoff, none of the patients were still on treatment. Ten patients (9%) had completed the 2-year treatment course.

The ORR was 11%, with 6 patients achieving a complete response and 6 having a partial response. The ORR was 15% in patients with PD-L1-positive tumors and 3% in those with PD-L1-negative tumors. 

The median duration of response was not reached, and 90% of responders were estimated to have a response lasting 24 months or longer.

The median progression-free survival (PFS) was 2.0 months. The PFS rate was 15% at 1 year and 9% at 2 years. The median PFS was 2.1 months in patients with PD-L1-positive tumors and 2.0 months in those with PD-L1-negative tumors.

The median overall survival (OS) was 11.9 months. The OS rate was 49% at 1 year and 26% at 2 years. The median OS was 12.1 months in patients with PD-L1-positive tumors and 11.0 months in those with PD-L1-negative tumors.

Treatment-related adverse events (TRAEs) were observed in 61% of patients. The most common were fatigue (15%), diarrhea (12%), hypothyroidism (12%), and nausea (12%).

Grade 3-4 TRAEs occurred in 18% of patients, and serious TRAEs occurred in 11%. Immune-mediated events occurred in 22% of patients, and 1% had infusion reactions. There were no grade 4-5 immune-mediated events or infusion reactions and no treatment-related deaths.

“In this analysis of patients with previously treated advanced anal squamous cell carcinoma, pembrolizumab monotherapy showed promising antitumor activity as shown by durable responses in a subset of patients, and encouraging overall survival, with a manageable safety profile,” the researchers wrote.

“These results suggest that 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.”

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

Reference

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