From Clinical Trial to Standard of Care: Pembrolizumab Plus Chemoradiotherapy Available at Moffitt
Treatment options for patients with locally advanced cervical cancer have remained largely unchanged for decades. Stage III-IVA cervical cancer is particularly challenging to treat. Unlike early-stage disease, these patients have limited options beyond chemoradiotherapy, which has served as the standard treatment for years. Surgery becomes less feasible, survival rates decline and recurrence poses a greater threat.
However, the introduction of immunotherapy into the curative-intent setting has prompted a meaningful shift in cervical cancer treatment. This shift centers on drugs like pembrolizumab, which activate the body's defenses against cancer. Combined with chemoradiotherapy, pembrolizumab shows real promise for patients with advanced disease who previously had few effective options.
KEYNOTE-A18 Trial
The Keynote-A18 trial studied pembrolizumab (brand name Keytruda, from Merck) paired with chemoradiotherapy (CRT) for patients with Stage III-IVA cervical cancer. This randomized, placebo-controlled study enrolled 1,060 patients who had not received definitive surgery, radiation, or systemic therapy across 175 study sites.
Participants were randomized to receive either pembrolizumab 200 mg or placebo every three weeks for five cycles plus chemoradiotherapy, followed by pembrolizumab 400 mg or placebo every six weeks for 15 cycles. The standard chemoradiotherapy protocol consisted of cisplatin 40 mg/m² for five cycles combined with external beam radiation therapy, followed by brachytherapy.
The study’s primary endpoints focused on progression-free survival and overall survival, helping to clearly demonstrate the clinical benefit for this patient population.
Clinical Results
The trial results were compelling: patients who got pembrolizumab alongside CRT fared much better than those on CRT alone, with a 30% lower risk of disease progression or death after 17.9 months of follow-up.
The 24-month progression-free survival rate was 67.8% for patients receiving pembrolizumab plus CRT versus 57.3% for those receiving the placebo and CRT.
As for overall survival, the 36-month OS was 86.2% with the combination therapy, compared to 74.8% with CRT alone.
The safety profile of pembrolizumab plus chemoradiotherapy proved consistent with the known effects of the individual components. Grade 3 or higher adverse events occurred in 75% of patients in the pembrolizumab-CRT group compared to 69% in the CRT-alone group. The most common adverse reactions included nausea, gastrointestinal issues, UTI or pain urinating, fatigue, hypo- and hyper-thyroidism, decreased appetite, weight loss, rash, and pelvic or abdominal pain. Most adverse events are manageable with corticosteroids for immune-related toxicities or supportive care for other side effects like fatigue or gastrointestinal issues.
FDA Approval and Clinical Implications
Dr. Jing-Yi Chern, a gynecologic oncologist in the Gynecologic Oncology Program at Moffitt, shared, "The treatment for locally advanced cervical cancer has not changed in many, many years. The KEYNOTE-A18 study, which just came out with finalized overall survival data, is really impressive. It sets a new bar that we should be treating patients with pembrolizumab and chemotherapy with their radiation, as it does improve their survival,” she said. “This is huge. These treatments should be considered standard of care therapy."
The results mark the first significant advancement in treatment for FIGO 2014 Stage III-IVA cervical cancer in decades.
The FDA approved pembrolizumab in combination with chemoradiotherapy for locally advanced cervical cancer on January 12, 2024. This approval built upon pembrolizumab's 2021 approval for recurrent or metastatic cervical cancer in patients whose tumors express PD-L1 protein.
Data from KEYNOTE-A18 and the KEYNOTE-826 trial demonstrate that adding pembrolizumab to chemotherapy or chemoradiotherapy can benefit patients regardless of PD-L1 expression, expanding the treatment's applications across a broader patient population.
Current Status
When implementing this treatment, Moffitt’s medical oncology, radiation oncology and gynecologic oncology teams coordinate to ensure appropriate patient selection and optimal treatment planning.
Moffitt’s Advanced Care
Pembrolizumab combined with chemoradiotherapy has delivered impressive results, including improved long-term survival, making a strong case for immunotherapy in cervical cancer care.
This success opens doors for more immunotherapy research in cervical cancer. There’s potential for further therapeutic discoveries in the years ahead, and hope for what these advancements could bring.
For healthcare providers managing patients with newly diagnosed cervical cancer, early referral for comprehensive evaluation ensures access to the most current standard of care. Moffitt Cancer Center's multidisciplinary cervical cancer program provides evidence-based treatment options, including pembrolizumab plus chemoradiotherapy for eligible patients.
To refer a patient to Moffitt, complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are normally responded to within 24 - 48 hours.
