As reported in the Journal of Clinical Oncology by Jean-Sebastien Frenel, MD, of the Institut de Cancerologie de l’Ouest, Centre Rene Gauducheau, Saint-Herblain, France, and colleagues, pembrolizumab (Keytruda) treatment was found to be active in patients with programmed cell death ligand 1 (PD-L1)–positive advanced cervical cancer in the phase Ib KEYNOTE-028 trial.1
In the advanced cervical cancer cohort of the trial, 24 patients received pembrolizumab at 10 mg/kg every 2 weeks for up to 24 months. Response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary endpoint was overall response rate.
[R]esults 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.— Jean-Sebastien Frenel, MD and colleagues
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Patients had a median age of 42 years (range = 26–62 years), 92% had received prior radiation therapy, and 63% had received ≥ 2 lines of therapy for advanced disease, including bevacizumab (Avastin) in 42%. All patients had metastatic disease, including disease in the lymph nodes (n = 16; 67%), lung (n = 9; 38%), pelvis (n = 9; 38%), and liver (n = 6; 25%). 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 and Survival
At data cutoff, median follow-up was 11.0 months (range = 1.3–32.2 months). A partial response was observed in four patients (17%), with an additional three patients (13%) having stable disease. Median time to response was 1.9 months (range = 1.7–8.2 months).Median duration of response was 5.4 months (range = 4.1–7.5 months), with 2 patients having a response > 6 months.
One patient had a response at a previously irradiated site. A decrease in the sum of diameters of target lesions was observed in 8 (36%) of 22 evaluable patients on computed tomography. All 4 responders had PD-L1 expression on the tumor only.
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.
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 5 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.
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. Treatment was discontinued due to treatment-related adverse events in two patients (8%), consisting of colitis and Guillain-Barré syndrome. No treatment-related deaths were observed.
The investigators concluded: “[R]esults 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 safety and clinical benefit of pembrolizumab in advanced cervical cancer are currently under investigation in the open-label, phase II, multicohort KEYNOTE-158 trial.” ■
DISCLOSURE: The study was funded by Merck & Co, Inc. For full disclosures of the study authors, visit jco.ascopubs.org.
1. Frenel J-S, Le Tourneau C, O’Neil B, et al: Safety and efficacy of pembrolizu-mab in advanced, programmed death ligand 1–positive cervical cancer: Results from the phase Ib KEYNOTE-028 trial. J Clin Oncol. November 2, 2017 (early release online).
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