Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study
Mené sur 112 patients atteints d'un carcinome épidermoïde de l'anus de stade avancé (81 % de femmes), cet essai non randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du pembrolizumab, après l'échec de traitements standard
Background : Outcomes in advanced anal squamous cell carcinoma are poor, with few treatment optionsand controlled clinical trials. We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2KEYNOTE-158 study.
Methods : Eligible patients enrolled in the ongoing non-randomised, multicohort, multicentre,phase 2 KEYNOTE-158 study, which was done across 38 centres worldwide, were aged 18years or older; had histologically or cytologically confirmed advanced or metastaticanal squamous cell carcinoma; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a PD-L1-evaluable tissue sample. Patient sreceived pembrolizumab 200 mg intravenously every 3 weeks for 2 years, or until disease progression, unacceptable toxicity, investigator's decision to withdraw the patientfrom the study, or withdrawal of patient consent. The primary endpoint was objective response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1.Efficacy and safety analyses included all patients who received at least one doseof pembrolizumab. The trial is registered with ClinicalTrials.gov, NCT02628067.
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 tumours. The median timefrom first dose to data cutoff (June 27, 2019) was 34·7 months (IQR 32·5–36·4). 12(11%, 95% CI 6–18) patients had an objective response, including 11 (15%, 8–25) of75 patients with PD-L1-positive tumours and one (3%; 0–17) of 30 patients with PD-L1-negativetumours. 68 (61%) patients had treatment-related adverse events (20 [18%] patientshad grade 3–4 adverse events), the most common of which were fatigue (17 patients),diarrhoea (13), hypothyroidism (13), and nausea (13). Serious treatment-related adverseevents occurred in 12 (11%) patients. 25 (22%) patients had immune-mediated adverseevents, and one (1%) had an infusion reaction. There were no treatment-related deaths.
Interpretation : Pembrolizumab monotherapy is a possible treatment option with a favourable benefit–riskratio for patients with previously treated advanced anal squamous cell carcinoma whohave no alternative satisfactory treatment options.
The Lancet Gastroenterology & Hepatology , résumé, 2021