Pembrolizumab Shows Activity in Advanced Cervical Cancer

The immune checkpoint inhibitor pembrolizumab demonstrated antitumor activity in a small trial of patients with advanced cervical cancer. The agent had a similar toxicity profile to that seen in other malignancies.

Though patients who present with localized cervical cancer have a good prognosis, this is not the case in those who present with advanced disease. “The prognosis for patients with advanced disease is poor, with a 5-year survival rate of only 17%,” wrote study authors led by Jean-Sébastien Frenel, MD, of the Institut de Cancérologie de l’Ouest in Saint-Herblain, France. Limited treatment options are currently available for these patients, but it was recently determined that PD-L1 is expressed in cervical cancer, suggesting that pembrolizumab may be effective.

The KEYNOTE-028 trial included 20 cohorts of different malignancies; the cervical cancer cohort included 24 patients with a median age of 42 years. Most of these patients (92%) had received prior radiation therapy, and 63% had received at least two prior lines of therapy for advanced disease. The results of the analysis were published online ahead of print in the Journal of Clinical Oncology.

After a median follow-up of 11 months, the overall response rate was 17%; all four responders had a partial response, and another three patients had stable disease (13%). Sixteen patients had progressive disease (67%).

The median time to response among those who did achieve a partial response was 1.9 months, and the median duration of response was 5.4 months; two of the four responders maintained a response for over 6 months. All four responders demonstrated PD-L1 expression in the tumor only.

The median progression-free survival in all patients was 2 months, and the progression-free survival rate at 6 and 12 months was 21% and 4%, respectively. The median overall survival was 11 months, and the 6- and 12-month overall survival rates were 67% and 40%, respectively.

A total of 18 patients had adverse events considered related to the study drug; the most common were rash (21%) and pyrexia (17%). Five patients had grade 3 treatment-related adverse events, and these included neutropenia, rash, colitis, Guillain-Barre syndrome, and proteinuria. Four patients (17%) experienced a serious adverse event that was considered treatment-related.

“Results from this analysis of the phase Ib KEYNOTE-028 trial suggest that pembrolizumab is well tolerated and has durable antitumor activity in patients with PD-L1-positive advanced cervical cancer,” the authors concluded. The KEYNOTE-0158 phase II trial is now underway in this setting, and the value of PD-L1 immunohistochemistry as a biomarker is also being assessed.