In phase Ib results from the KEYNOTE-028 trial, pembrolizumab (Keytruda) was active in cervical cancer while demonstrating safety results similar to previous studies with the PD-1 inhibitor.
Four of 24 women in the study had confirmed partial responses (PR), for an overall response rate (ORR) of 17% (95% CI, 5%-37%). Three patients had stable disease (13%; 95% CI, 3%-32%), and 16 had progressive disease (67%; 95% CI, 45%-84%) as best response.
KEYNOTE-028 is a multicenter, phase Ib, single-arm trial evaluating the safety and efficacy of pembrolizumab in 20 different PD-L1–positive advanced solid tumors. These results come from an analysis of 24 women with PD-L1¬–positive advanced cervical cancer. Eighteen patients (75%) expressed PD-L1 in the tumor only and 6 (25%) were PD-L1–positive in the tumor and stroma.
Patients were assigned to 10 mg/kg pembrolizumab as a 30-minute intravenous (IV) infusion every 2 weeks for up to 24 months or until withdrawal of consent, confirmed radiographic progression, unacceptable toxicity, or investigator decision. Participants with stable disease or better at treatment discontinuation could restart pembrolizumab treatment for up to 1 year if they exhibited subsequent disease progression.
Treatment could be withheld for patients exhibiting intolerable or persistent grade 2 treatment-related adverse events (AEs). Patients were taken off treatment if the toxicity did not resolve to grade 0 to 1 within 12 weeks.
All patients presented with metastatic disease, which was most frequently located in the lymph nodes (67%), lung (38%), pelvis (38%), and liver (25%). Twenty-two patients (92%) received prior radiation therapy and 15 (63%) had received 2 or more lines of chemotherapy for advanced disease. All but 1 patient had received platinum-based chemotherapy before study initiation, and 10 of 24 patients (42%) had received prior bevacizumab (Avastin).
Eight of 22 patients (36%) evaluable by CT scan experienced a decrease in the sum of diameters of target lesions from baseline. These decreases in patients were maintained over time in patients who had a PR.
Median progression-free survival (PFS) in all patients was 2 months (95% CI, 2-3). PFS was 21% at 6 months and 4% at 12 months. Median overall survival (OS) in all patients was 11 months (95% CI, 4-15). OS rate at 6 months was 67% and 40% at 12 months.
Median time to response in the 4 patients who achieved PR was 1.9 months (range, 1.7-8.2). Median duration of response (DOR) for responders was 5.4 months (range, 4.1-7.5). Two of the 4 patients who had PR exhibited a response for more than 6 months. Tumor samples from all 4 patients with PRs had PD-L1 expression in the tumor only.
At the time of the data cutoff, median follow-up was 11.0 months (range, 1.3-32.2 months). Eighteen patients experienced AEs related to pembrolizumab treatment. Rash (21%) and pyrexia (17%) affected ≥10% of patients.
All patients discontinued treatment during the study, 4 (17%) because of AEs, 1 (4%) because of physician decision, and 19 (79%) because of progressive disease.
Five patients experienced grade 3 treatment-related AEs including neutropenia, rash, colitis, Guillain-Barre ́ syndrome, and proteinuria. There were no grade 4 treatment-related AEs and no treatment-related deaths in the study.
Four patients (17%) experienced serious AEs that were considered treatment related, including 1 case each of grade 3 rash, colitis, and Guillain-Barre ́ syndrome, and 1 incidence of grade 2 pyrexia. Two patients discontinued treatment because of grade 3 treatment-related colitis and Guillain-Barre ́ syndrome. After discontinuation, the patient with Guillain-Barre ́ syndrome recovered after treatment with tegeline.
Six patients experienced immune-mediated AEs including grade 3 rash (n = 2), colitis (n = 1), and Guillain-Barre ́ syndrome (n = 1), and 1 each of grade 2 hyperthyroidism and hypothyroidism.
Frenel JS, Le Tourneau C, O’Neil, B, et al. Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1–positive cervical cancer: Results from the phase Ib KEYNOTE-028 trial [published online ahead of print November 2, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.74.5471.