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Pembrolizumab (Keytruda) monotherapy demonstrated promising antitumor activity, with durable responses, in patients with previously treated advanced anal squamous cell carcinoma, the phase II KEYNOTE-158 study found.

Among 112 patients, objective responses were observed in 12 (11%, 95% CI 6-18), including six with a complete response, after a median follow-up of 34.7 months, reported Aurelien Marabelle, MD, of Gustave Roussy Cancer Center in Villejuif, France.

The responders included 11 of 75 patients with PD-L1-positive tumors and one of 30 patients with PD-L1-negative tumors, they noted in .

"These results suggest that pembrolizumab monotherapy is a possible treatment option" for patients "who have no alternative satisfactory treatment options," the authors wrote.

Median duration of response was not reached, and median overall survival (OS) was "encouraging," at 11.9 months (95% CI 9.1-14.9), Marabelle and team said. The 12- and 24-month OS rates were estimated to be 49% and 26%, respectively.

Median OS was 12.1 months (95% CI 9.1-15.7) in patients with PD-L1-positive tumors and 11.0 months (95% CI 4.5-19.9) in those with PD-L1-negative tumors.

While the trial's results are encouraging, they raise several questions, observed Astrid Lièvre, MD, PhD, of Pontchaillou University Hospital in Rennes, France, in a .

She noted that only a small subset of patients (11%) responded to the PD-1 blockade. "Therefore, efforts should now focus on identifying responder patients who might benefit from immunotherapy for anal squamous cell carcinoma," she wrote.

"The study suggests a higher objective response in patients with PD-L1-positive tumors than in PD-L1-negative tumors," she added. "However, these data should be interpreted with caution: the improved objective response had no effect on survival; previous studies do not support such a predictive value of PD-L1 expression, as they reported similar objective responses regardless of PD-L1 status; and the definition of PD-L1-positive status is not standardized."

KEYNOTE-158 was an international, open-label, non-randomized study that was conducted across 38 centers to evaluate pembrolizumab in patients with various rare advanced solid tumor types. This analysis included patients ages 18 and older with histologically or cytologically confirmed advanced or metastatic anal squamous cell carcinoma from the study's cohort A.

From March 2016 to July 2018, 112 patients were enrolled; median age was 61, 81% were women, 93% had M1 disease, and 67% had PD-L1-positive tumors.

All patients had previous failure of or intolerance to standard therapy or no standard therapy options. They 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.

As for safety, 61% of patients had treatment-related adverse events (TRAEs), and 18% had grade 3/4 adverse events, the most common of which were fatigue (17 patients), diarrhea (13), hypothyroidism (13), and nausea (13). Serious TRAEs occurred in 11% of patients, and 22% of patients had immune-mediated adverse events. There were no treatment-related deaths.

The study had a few limitations, Marabelle and colleagues acknowledged. Of note, data related to human papillomavirus, a known risk factor for anal carcinoma, were not available.

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