Pembrolizumab Continues to Improve PFS in Cervical Cancer

New results from the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study showed that a combination of pembrolizumab and concurrent chemoradiotherapy (CCRT) continues to improve progression-free survival (PFS) in locally advanced cervical cancer.

Initial results found that among 1060 participants in 30 countries, the pembrolizumab plus CCRT group conferred better PFS at 24 months than the placebo plus CCRT group (68% vs 57%; hazard ratio [HR], 0.70; P = .0020). Among the new findings presented was that the secondary endpoint of PFS at 36 months (PFS2; median, 29.9 months) was reached. The updated PFS rate remained higher in the treatment arm than in the placebo arm (62.7% vs 54.5%; HR, 0.68; 95% CI, 0.56-0.84).

According to Linda Duska, MD, who presented the study, the finding represents the first true advance in therapy since 1999, when the standard therapy became weekly cisplatin plus external beam radiation, followed by brachytherapy.

Duska displayed the Kaplan-Meier curves, which showed sustained separation in PFS beginning at 3 months, when the first post-CCRT imaging was obtained.

“The safety profile was manageable and consistent with known profiles of the individual therapies, with no new safety signals. These data support the use of this combination regimen as the new standard of care for patients with high risk locally advanced cervical cancer and as a potential appropriate control arm in future clinical trials,” said Duska, who is a professor of obstetrics and gynecology at the University of Virginia School of Medicine, Charlottesville, Virginia, during a talk at Society of Gynecologic Oncology Annual Meeting on Women’s Cancers (SGO) 2025.

Initial Results

Duska noted that the PD-L1 inhibitor pembrolizumab has shown efficacy in the treatment of recurrent or metastatic cervical cancer and received approval from the US Food and Drug Administration, the European Commission, and other worldwide regulatory authorities to treat patients with FIGO 2014 stage III-IVA cervical cancer.

Those approvals were based on the initial results of ENGOT-cx11/GOG-3047/KEYNOTE-A18. Among those results was that at 24 months, overall survival (OS) was higher in the pembrolizumab group than in the placebo group, though the difference did not reach statistical significance (87% vs 81%; HR, 0.73; 95% CI, 0.49-1.07).

Eligible patients had high-risk locally advanced cervical cancer, defined as FIGO stage IB2-IIB or FIGO 2014 stage III-IVA disease, regardless of the node status. Patients were randomly assigned to receive either standard cisplatin radiation plus pembrolizumab or placebo.

Subgroup Analysis

Duska highlighted results from the IB2 to IIB subgroup analysis; patients who are now classified as FIGO 2018 stage IIIC, based on positive retroperitoneal lymph nodes. In that group, the HR decreased from 0.91 in the first interim analysis to 0.85 in the second, though neither result was statistically significant.

“These subgroup analyses were not powered and should be considered hypothesis-generating,” said Duska.

The study showed improved OS at 3 years in the pembrolizumab vs placebo group (82.6% vs 74.8%; HR, 0.67; P = .0040).

“As before, the [Kaplan-Meier] curves start separating this time at about 10 months and continue to remain separated over the follow-up period. The OS results across all pre-specified subgroups were generally consistent with the overall intention to treat population,” said Duska.

The follow-up study also showed encouraging adverse event data. “Despite an initial concern of overlapping toxicities with diarrhea and colitis, we did not see a difference between these events in the arms,” said Duska.

After the presentation, Premal Thaker, MD, who served as a discussant, said the findings make the study protocol “the new standard of care for our high-risk locally advanced cervical cancer patients.”

“I believe we have really moved the needle for women with locally advanced cervical cancer with the inclusion of pembrolizumab. However, we must make sure that all cervical cancer patients have equal, equitable benefits from these advances, both here in the US and globally,” said Thaker, who is a professor of obstetrics and gynecology at Siteman Cancer Center.

Moore consulted for or advised Genentech/Roche, ImmunoGen, AstraZeneca, VBL Therapeutics, Merck, Eisai, Mersana, Myriad Genetics, Alkermes, Blueprint Medicines, GlaxoSmithKline/Tesaro, OncXerna Therapeutics, Onconova Therapeutics, Mereo BioPharma, Novartis, Verastem/Pharmacyclics, Aadi, Clovis Oncology, Caris Life Sciences, Hengrui Pharmaceutical, Novartis/Pfizer, Iovance Biotherapeutics, Duality Biologics, Janssen Oncology, Regeneron, and Zentalis.

Thakar received research funding from PTC Therapeutics, Lilly, Merck, Tesaro, Genentech, Clovis Oncology, Lilly Foundation, Regeneron, Bristol Myers Squibb, Verastem, Novartis Pharmaceuticals UK Ltd, AstraZeneca, Agenus, Takeda, ImmunoGen, Novogen, Artios, Bolt Biotherapeutics, Amgen, Daiichi Sankyo/Lilly, Cyteir, and Immunocore.

Thaker consulted for AstraZeneca, GlaxoSmithKline, Merck, Pfizer, Corcept, Zentalis, Verastem, and Imunon.