Linda Duska, MD, MPH
An international clinical trial’s U.S. arm, led by Linda Duska, MD, MPH, professor of obstetrics and gynecology and associate dean of clinical research at the UVA School of Medicine, is already changing how cervical cancer is treated at UVA and throughout the nation.
The phase III KEYNOTE-A18 trial combines the immunotherapy drug pembrolizumab, known by the brand name Keytruda, with concurrent chemoradiotherapy treatment (CCRT) for patients with FIGO 2014 high-risk, locally advanced stage IB or II cervical cancer with positive lymph node metastasis, or FIGO 2014 stage III-IVa disease.
For a quarter century, the standard of care for locally advanced cervical cancer (LACC) was CCRT – chemotherapy and external-beam radiation – followed by brachytherapy.
In 2024, the FDA approved the trial’s combination therapy for FIGO 2014 stage III-IVA disease, and the study’s improved survival findings were published in The Lancet and presented by Domenica Lorusso, MD, PhD, of Fondazione Policlinico Universitario A. Gemelli IRCCS and Humanitas San Pio X at the European Society for Medical Oncology Congress.
This March, Dr. Duska presented updated findings to the 2025 Society of Gynecologic Oncology Annual Meeting. She reported that after three years, patients who received the combination therapy had a 33 percent reduction in the risk of death, a 32 percent reduced risk of disease progression, and a 40 percent reduced risk of second disease progression, defined as time from random assignment to subsequent disease progression after initiation of new anticancer therapy or death.
“These data support pembrolizumab plus CCRT as the new standard of care for patients with newly diagnosed, previously untreated high-risk locally advanced cervical cancer,” Dr. Duska said, “and as a potential appropriate control arm in future clinical trials.”
In the study, 1,060 participants received five cycles of pembrolizumab or placebo every three weeks, plus CCRT, followed by maintenance pembrolizumab or placebo.
An immunotherapy drug, pembrolizumab enlists patients’ immune system to fight cancer. Some cancers can “turn off” the PD-1 pathway that immune T cells use to find and combat infections and diseases. When that happens, cancer effectively hides from the immune system. Pembrolizumab blocks cancer cells from turning off the PD-1 pathway so a patient’s immune system can recognize them and fight back. It is indicated for various diseases, including cervical, non-small cell lung, colon and rectal cancers and melanoma.
Dr. Duska emphasized that one piece of the research puzzle is the most vital to progress in treating cancer: clinical trials, without which the advantage pembrolizumab contributes would not have been achieved. “In cancer, clinical research and care are the same thing because trials allow patients to get novel therapies and for clinicians to learn,” she said.
Launched in 2020, the KEYNOTE-A18 trial reported final results at the American Society of Clinical Oncology (ASCO) on June 2, 2025.