Linda R. Duska, MD, MPH, is a gynecologic oncologist at the University of Virginia Health.

Dr Duska on the Adoption of Pembrolizumab Plus Concurrent CRT As a SOC in Advanced Cervical Cancer  

Dr Duska on the Adoption of Pembrolizumab Plus Concurrent CRT as a SOC in Advanced Cervical Cancer  

"The results of this study suggest that, for this patient population, pembrolizumab in combination with concurrent chemoradiation should be the SOC. However, there are parts of the world where this kind of treatment is not available; therefore, we have to continue to do more work and do better for patients with locally advanced cervical cancer."

Linda R. Duska, MD, MPH, a gynecologic oncologist at the University of Virginia Health, discusses the clinical implications of data from the second interim analysis of the phase 3 KEYNOTE-A18 trial (NCT04221945), and next steps for the evaluation of pembrolizumab (Keytruda) and chemoradiotherapy, followed by pembrolizumab, in patients with newly diagnosed, previously untreated, high-risk, stage IB2 to IIB, node-positive or stage III to IVA locally advanced cervical cancer.

Data from the second interim analysis of the phase 3 KEYNOTE-A18 trial (NCT04221945), which were presented at the 

2025 SGO Annual Meeting on Women’s Cancer

, demonstrated that the regimen produced statistically significant and clinically meaningful improvements in overall survival (OS) and time to second disease progression or death (PFS2), as well as a sustained progression-free survival (PFS) benefit compared with standard chemoradiotherapy alone. These data support a paradigm shift in the treatment of this high-risk population, for whom long-term outcomes with chemoradiotherapy alone have historically been poor.

Duska emphasized that these findings support the incorporation of pembrolizumab in combination with concurrent chemoradiotherapy as a new standard of care in appropriate settings. However, access to this combination remains a challenge in resource-limited settings, underscoring the need for global efforts to ensure equitable availability of advanced therapies, she noted.

Although data from the final analysis are still pending, Duska highlighted the importance of continuing research efforts in this space. In particular, she stressed the ongoing need to focus on prevention strategies, including HPV vaccination and improved screening, which remain critical for reducing the incidence of cervical cancer worldwide. As new data continue to emerge, further opportunities to refine treatment approaches and improve outcomes for patients with locally advanced cervical cancer are anticipated, Duska concluded.

Videos

Linda R. Duska, MD, MPH, discusses the need for continued research with concurrent chemoradiation in high-risk advanced cervical cancer.



Dr Duska on the Role of Immunotherapy With Definitive Treatment in High-Risk, Locally Advanced Cervical Cancer

"The study had two preplanned interim analyses. [The first was conducted] very early in the study, when the median follow-up was approximately 18 months. [At that time], the study met its PFS end point…The experimental arm had improved PFS over the placebo arm, even that early in the study, with a hazard ratio of around [0.7]. [That was very promising], and we were really excited about that."

Linda R. Duska, MD, MPH, professor of gynecologic oncology at the University of Virginia, highlighted the significance of incorporating immunotherapy into definitive treatment for patients with high-risk, locally advanced cervical cancer following the read out of final results from the phase 3 KEYNOTE-A18 trial (NCT04221945), which evaluated pembrolizumab (Keytruda) in combination with concurrent chemoradiotherapy (CRT) vs placebo plus CRT in this patient population.

Findings from the final analysis, which was descriptive in nature, that were presented at the 

 showed that at a median follow-up of 41.9 months, the pembrolizumab-based regimen reduced the risk of disease progression or death by 28% compared with the placebo regimen (HR, 0.72; 95% CI, 0.59-0.87). A similar benefit was observed regarding overall survival (OS; HR, 0.73; 95% CI, 0.57-0.94)

Duska noted that during the first preplanned interim analysis, conducted at a median follow-up of 18.2 months, the trial met its primary progression-free survival (PFS) end point (HR, 0.70; 95% CI, 0.55-0.89, 

 = .0020). Based on the study’s hierarchical statistical design, all alpha was initially allocated to PFS; following significance in this end point, testing proceeded to OS.

At the second interim analysis, conducted at a median follow-up of 29.9 months, the trial met the OS end point (HR, 0.67; 95% CI, 0.50-0.90; 

 = .0040), Duska emphasized that despite early censoring in both interim analyses, the data demonstrated consistent benefit across efficacy outcomes.

the FDA approved pembrolizumab plus chemoradiation

 for patients with FIGO 2014 stage III to IVA cervical cancer, based on prior data from KEYNOTE-A18.

Linda R. Duska, MD, MPH, on incorporating immunotherapy into definitive therapy for high-risk, locally advanced cervical cancer.

Dr Duska on the Efficacy of Pembrolizumab Plus Concurrent CRT in Advanced Cervical Cancer

Linda R. Duska, MD, MPH, a gynecologic oncologist at the University of Virginia Health, discussed efficacy outcomes with the combination of pembrolizumab (Keytruda) and chemoradiotherapy followed by pembrolizumab monotherapy, in patients with newly diagnosed, high-risk, stage IB2 to IIB, node-positive or stage III to IVA locally advanced cervical cancer.

the second interim analysis of the phase 3 KEYNOTE-A18 trial

 demonstrated that the combination regimen led to statistically significant and clinically meaningful improvements in overall survival (OS) and time to second disease progression or death (PFS2) compared with chemoradiotherapy plus placebo in this patient population. The data also showed a sustained progression-free survival (PFS) benefit with the combination, Duska reported.

At the second interim analysis, the median OS was not reached (NR) in both arms, with 14.2% of patients in the pembrolizumab arm experiencing an OS event compared with 20.5% of those in the placebo arm (HR, 0.67; 95% CI, 0.50-0.90; 

 = .0040). The 36-month OS rates were 82.6% (95% CI, 78.4%-86.1%) in the pembrolizumab arm compared with 74.8% (95% CI, 70.1%-78.8%) in the placebo arm.

Regarding PFS2, the median time to event was NR in both arms, with events occurring in 15.3% of patients in the pembrolizumab arm and 24.3% of those in the placebo arm (HR, 0.60; 95% CI, 0.46-0.80). The PFS data showed that 29.3% of patients in the pembrolizumab arm experienced a PFS event compared with 39.5% of those in the placebo arm. The median PFS was NR in both arms (HR, 0.68; 95% CI, 0.56-0.84). The 36-month PFS rates were 62.7% (95% CI, 56.4%-68.4%) in the pembrolizumab arm and 54.5% (95% CI, 49.3%-59.3%) in the placebo arm. These data are exciting as they represent a significant treatment advancement for patients with high-risk locally advanced cervical cancer, Duska concluded.

Linda R. Duska, MD, MPH, discusses OS and PFS2 outcomes with concurrent pembrolizumab and chemoradiotherapy in high-risk advanced cervical cancer. 



Linda R. Duska, MD, professor of obstetrics and gynecology and gynecologic oncologist at the University of Virginia, discusses primary debulking surgery in ovarian cancer.

Primary debulking surgery has demonstrated improved overall survival for patients. However, the procedure can lead to surgical complications. For example, primary debulking surgery has been associated with an increased rate of surgical morbidity or mortality in some patients, says Duska.

As such, patient-related factors including performance status, serum albumin levels, BMI, and other medical comorbidities may lead a surgeon to discuss neoadjuvant chemotherapy with the patient as a less morbid alternative to surgery, concludes Duska.

Linda R. Duska, MD, discusses primary debulking surgery in ovarian cancer.

Dr. Duska on Primary Debulking Surgery in Ovarian Cancer

Linda R. Duska, MD, professor of obstetrics and gynecology and gynecologic oncologist at the University of Virginia, explains whether the Fagotti score provides an accurate assessment of whether a patient with newly diagnosed, advanced ovarian cancer can achieve a complete resection in surgery.

The Fagotti score can be useful in determining whether a patient with newly diagnosed, advanced ovarian cancer can undergo optimal debulking surgery in the hands of an experienced surgeon, explains Duska. However, it is not the sole way to assess resectability. A small laparotomy could be performed instead, in addition to performing imaging, a CT scan, a PET scan, or an MRI, says Duska.

Ultimately, resectability should be assessed by a trained gynecologic oncologist. Having a gynecologic oncologist involved in the care of women with advanced disease from the onset of treatment is important, says Duska. However, that is not always possible, especially in community practices where general surgeons or gynecologists are more likely to perform the surgery. When that happens, the patient’s likelihood of receiving an appropriate surgery decreases, concludes Duska.

Dr. Duska on the Utility of the Fagotti Score in Advanced Ovarian Cancer

Linda R. Duska, MD, professor of obstetrics and gynecology, University of Virginia, discusses neoadjuvant chemotherapy versus upfront surgical debulking in patients with advanced ovarian cancer.

Many physicians believe that upfront surgical debulking is the best option for most patients with ovarian cancer; however, research is showing that there are subgroups of patients who benefit from neoadjuvant chemotherapy, explains Duska. Some studies suggest that neoadjuvant chemotherapy is equivalent to primary debulking surgery and may be less morbid, according to Duska.

Two studies examining neoadjuvant chemotherapy versus upfront surgical debulking enrolled women who were older, had bulkier disease, and poorer performance status. Duska says this is a different patient population than typical studies, and these studies have been criticized for low debulking rates. However, these data show that a certain subgroup of patients, such as those with stage IV disease, seem to benefit from neoadjuvant chemotherapy over primary debulking surgery, concludes Duska.

Linda R. Duska, MD, discusses neoadjuvant chemotherapy versus upfront surgical debulking in patients with advanced ovarian cancer.

Linda R. Duska, MD, MPH

Articles

Dr Duska on the Adoption of Pembrolizumab Plus Concurrent CRT as a SOC in Advanced Cervical Cancer

Dr Duska on the Role of Immunotherapy With Definitive Treatment in High-Risk, Locally Advanced Cervical Cancer

Dr Duska on the Efficacy of Pembrolizumab Plus Concurrent CRT in Advanced Cervical Cancer

Dr. Duska on Primary Debulking Surgery in Ovarian Cancer

Dr. Duska on the Utility of the Fagotti Score in Advanced Ovarian Cancer

Dr. Duska on Neoadjuvant Chemo Vs Upfront Surgery in Ovarian Cancer