Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1–Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial

Abstract

Purpose The KEYNOTE-028 trial ( ClinicalTrials.gov identifier: NCT02054806) was designed to assess the safety and efficacy of pembrolizumab in 20 programmed death ligand 1-positive, advanced solid tumor cohorts. Here, we present the results from the cohort of patients with advanced cervical cancer. Methods Patients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 months. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end point was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, by investigator review. Safety was a secondary end point. Results Twenty-four patients were enrolled in the cervical cancer cohort. The median age was 42 years (range, 26 to 62 years), 22 patients (92%) had received prior radiation therapy, and 15 patients (63%) had received two or more lines of therapy, including bevacizumab (10 of 24 patients), for advanced disease. At the data cutoff, median follow-up duration was 11.0 months (range, 1.3 to 32.2 months). Overall response rate was 17% (95% CI, 5% to 37%); four patients (17%) achieved a confirmed partial response, and three patients (13%) had stable disease. Median duration of response for the four patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). Treatment related adverse events (AEs) were experienced by 18 patients (75%); only rash (n = 5; 21%) and pyrexia (n = 4; 17%) and occurred in ≥ 10% of patients. Five patients experienced grade 3 treatment-related AEs. No grade 4 treatment-related AEs or deaths were observed. Conclusion In patients with programmed death ligand 1-positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types.

Bevacizumab in Metastatic, Recurrent, or Persistent Cervical Cancer: The BC Cancer Experience

“…The majority of these patients had progressed on first -line therapy. 25 Likewise, the KEYNOTE-028 and KEYNOTE-158 trials 26,27 reported on more than 100 patients with programmed death ligand 1Yexpressing recurrent cervical cancer, all of whom had had prior treatment for advanced disease. Treatment with pembrolizumab led to an overall RRs of~15%, with an addi-tional~15% experiencing SD.…”

Activity of Pembrolizumab in Recurrent Cervical Cancer

“…In contrast to the KEYNOTE-028 and Checkmate 358 study, we treated patients irrespective of overexpression of PD-L1 and found similar response rates. 10,14 This is not surprising because the accuracy of PD-L1 expression in predicting treatment response remains controversial. The PD-L1 expression analysis is still an area of active study, and varying results have been reported with different antibodies, staining platforms, and scoring criteria.…”

“…A tumor proportion score of more than 1% was considered positive based on previous studies. 9,10 A baseline computed tomography (CT) scan was performed, and primary target lesions were identified and measured. Clinicopathological data at initial diagnosis and at time of last recurrence were assessed.…”

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature

“…Pembrolizumab has rarely been utilized in the gynecologic setting; however, it has been reported to have a favorable safety profile and durable antitumor activity in cervical and endometrial cancer [39][40][41] as well as gestational trophoblastic neoplasia [42]. Several toxicities have been encountered with pembrolizumab such as fatigue, nausea, myalgia, arthralgia, and colitis [31,35,37].…”