In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms of action, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.
On October 13, 2021, pembrolizumab in combination with chemotherapy with or without bevacizumab was approved for the first-line treatment of patients with persistent, recurrent, or metastatic cervical cancer with a tumor PD-L1 combined positive score (CPS) ≥ 1, as determined by a U.S. Food and Drug Administration (FDA)-approved test.1
Pembrolizumab was also granted regular approval as single-agent treatment for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy with a tumor PD-L1 CPS ≥1, as determined by an FDA-approved test, following accelerated approval in June 2018.
Supporting Efficacy Data
Approval was supported by the phase III double-blind KEYNOTE-826 trial (ClinicalTrials.gov identifier NCT03635567). In the trial, 616 patients were randomly assigned (irrespective of PD-L1 status) to receive pembrolizumab at 200 mg (n = 307) or placebo (n = 309) plus chemotherapy (paclitaxel plus cisplatin or carboplatin) with or without bevacizumab in 3-week cycles.
Among 273 patients in the pembrolizumab group vs 275 in the control group with a tumor PD-L1 CPS ≥ 1, median overall survival was not reached (95% confidence interval = 19.8 months to not reached) vs 16.3 months (95% CI = 14.5–19.4 months; hazard ratio [HR] = 0.64, 95% CI = 0.50–0.81, P = .0001). Median progression-free survival was 10.4 months (95% CI = 9.7–2.3 months) vs 8.2 months (95% CI = 6.3–8.5 months; HR = 0.62, 95% CI = 0.50–0.77, P < .0001). Objective response rate was 68% vs 50%; median response duration was 18.0 vs 10.4 months.
How It Is Used
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.
No dose reductions of pembrolizumab are recommended. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
Among the total of 616 patients in KEYNOTE-826, the most common adverse events of any grade in the pembrolizumab group were peripheral neuropathy (58% vs 57% in the control group), alopecia (56% vs 58%), fatigue (47% vs 46%), nausea (40% vs 44%), and diarrhea (36% vs 30%). The most common grade 3 or 4 adverse events included urinary tract infection (9% vs 8%) and hypertension (9% vs 11%). The most common grade 3 or 4 laboratory abnormalities were neutropenia (39% vs 31%) and anemia (35% vs 33%).
Serious adverse events occurred in 50% of the pembrolizumab group, most commonly febrile neutropenia (6.8%) and urinary tract infection (5.2%). Adverse events led to discontinuation of pembrolizumab in 15%, most commonly because of colitis (1%). Fatal adverse events occurred in 4.6% of the pembrolizumab group, most commonly because of hemorrhage (three patients).
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity.
1. Keytruda (pembrolizumab) injection for intravenous use prescribing information, Merck & Co, Inc, October 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s121s122lbl.pdf. Accessed November 4, 2021.