On January 12, 2024, pembrolizumab (Keytruda) was approved for use with chemoradiotherapy for treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III–IVA cervical cancer.1
Supporting Efficacy Data
Approval was based on findings in the double-blind KEYNOTE-A18 study (ClinicalTrials.gov identifier NCT04221945). A total of 1,060 patients with no previous definitive surgery, radiation, or systemic therapy were randomly assigned to receive pembrolizumab at 200 mg or placebo every 3 weeks for 5 cycles plus chemoradiotherapy, followed by pembrolizumab at 400 mg or placebo every 6 weeks for 15 cycles. Chemoradiotherapy consisted of cisplatin at 40 mg/m2 weekly for five cycles and external beam radiation therapy followed by brachytherapy.
OF NOTE
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
Among all patients, the trial showed a significant improvement in progression-free survival in the pembrolizumab group vs the control group. Among 596 patients with FIGO 2014 stage III–IVA disease, progression-free survival events occurred in 21% of 293 patients in pembrolizumab group vs 31% of 303 patients in the control group (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.43–0.82). Among 462 patients with FIGO 2014 stage IB2–IIB, node-positive disease, the hazard ratio for progression-free survival for the pembrolizumab group vs control group was 0.91 (95% CI = 0.63–1.31), indicating that the progression-free survival improvement in the overall population was primarily attributed to patients with FIGO 2014 stage III–IVA disease. Overall survival data were not mature at time of analysis.
How It Is Used
The recommended dosing regimen for pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months. Pembrolizumab should be administered before chemoradiotherapy when given on the same day.
Safety Profile
Among the patients with FIGO 2014 stage III–IVA disease in KEYNOTE-A-18, the most common adverse events of any grade in the pembrolizumab group were nausea (56% vs 60% in control group), diarrhea (50% vs 50%), vomiting (33% vs 34%), and urinary tract infection (32% vs 31%); hypothyroidism occurred in 20% vs 5%. The most common grade 3 or 4 adverse events included urinary tract infection (4.1% vs 4.6%) and diarrhea (3.8% vs 4.3%). The most common grade 3 or 4 laboratory abnormalities in both groups were hematologic adverse events.
Serious adverse events occurred in 30% of patients in the pembrolizumab group, most commonly urinary tract infection (2.7%). Adverse events led to discontinuation of pembrolizumab in 7% of patients, most commonly diarrhea (1%). Fatal adverse events occurred in 1.4%, including one case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage.
KEY POINTS
- Pembrolizumab was approved for use with chemoradiotherapy for treatment of patients with FIGO 2014 stage III–IVA cervical cancer.
- The recommended dosing regimen for pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, and solid organ transplantation rejection; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving pembrolizumab.
REFERENCE
1. Keytruda (pembrolizumab) injection, for intravenous use, prescribing information, Merck & Co, Inc, January 2024. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s124lbl.pdf. Accessed January 31, 2024.
