IMMUNOTHERAPY FOR CERVICAL CANCER

Pembrolizumab (Keytruda) treatment was active in patients with programmed cell death ligand 1 (PD-L1)–positive advanced cervical cancer enrolled in the phase Ib KEYNOTE-028 trial. The findings were reported by Frenel et al in the Journal of Clinical Oncology.

Study Details

In the advanced cervical cancer cohort, 24 patients received pembrolizumab at 10 mg/kg every 2 weeks for up to 24 months. Response according to the Response Evaluation Criteria in Solid Tumors v1.1 was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary endpoint was overall response rate.

The median age of patients was 42 years (range = 26–62 years); 92% had received prior radiation therapy; and 63% had received at least 2 lines of therapy for advanced disease, including bevacizumab (Avastin) in 42%. PD-L1 positivity was defined as membranous staining ≥ 1%; 18 patients were PD-L1–positive in the tumor only and 6 were PD-L1–positive in the tumor and stroma.

Response Rate

At data cutoff, the median follow-up was 11.0 months (range = 1.3–32.2 months). Partial response was observed in four patients (17%), with an additional three patients (13%) having stable disease. The median time to response was 1.9 months (range = 1.7–8.2 months). The median duration of response was 5.4 months (range = 4.1–7.5 months), with 2 patients having response > 6 months. All four responders had PD-L1 expression on the tumor only. The median progression-free survival was 2 months, with rates of 21% and 4% at 6 and 12 months. Median overall survival was 11 months, with rates of 67% and 40% at 6 and 12 months.

Adverse Events

Treatment-related adverse events of any grade occurred in 75% of patients, with the most common being rash (21%) and pyrexia (17%). Treatment-related grade ≥ 3 adverse events occurred in five patients (21%, all grade 3), with rash occurring in 8%. Treatment-related serious adverse events occurred in four patients (17%), including one case each of rash, colitis, Guillain-Barré syndrome, and pyrexia. Treatment was discontinued due to treatment-related adverse events in two patients (8%), consisting of colitis and Guillain-Barré syndrome. Immune-mediated adverse events occurred in six patients (25%), including rash in two, colitis in one, Guillain-Barré syndrome in one, hyperthyroidism in one, and hypothyroidism in one. No treatment-related deaths were observed.

The investigators concluded: “In patients with programmed [cell] death ligand 1–positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types.”

The study was funded by Merck & Co., Inc.