Ahead of the meeting, the trial was noted for restricting enrollment to patients with dMMR disease, in contrast with the phase 3 KEYNOTE-B21 trial (NCT04634877), which evaluated pembrolizumab in an all-comers population.2<\/p>\n
How was NRG-GY020 designed?<\/p>\n
Eligible patients had stage I\/II endometrioid endometrial cancer meeting GOG 249 high-intermediate\u2013risk criteria based on age, grade, depth of invasion, and lymphovascular space invasion (LVSI); dMMR status by immunohistochemistry and\/or microsatellite instability on local testing; surgical staging with hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node assessment with or without full lymphadenectomy; an ECOG performance status of 0 to 2; and no measurable disease outside the uterus.1<\/p>\n
Patients were randomly assigned 2:1 to receive vaginal brachytherapy and\/or external beam radiation therapy with or without pembrolizumab, stratified by radiation type. Vaginal brachytherapy was the default; physician choice of external beam radiation was permitted only for patients with stage IB grade 3 or stage II disease. Radiation began 4 to 9 weeks after surgery. Pembrolizumab was initiated within 7 days before the start of radiation and given for up to 1 year, initially at 200 mg intravenously every 3 weeks; in September 2020, during the COVID-19 pandemic, dosing changed to 400 mg every 6 weeks, reducing the number of cycles from 17 to 9.<\/p>\n
The primary end point was the percentage of patients who were recurrence free at 3 years per RECIST 1.1 criteria by investigator assessment, analyzed as a dichotomized end point. Patients who died, recurred, or came off study within 3 years for any reason, as well as patients who remained censored at less than 3 years, were considered treatment failures. The study had 89% power to detect a 15% increase in 3-year RFS, from 80% to 95%. Secondary end points included safety, recurrence patterns, RFS and overall survival (OS) at 5 years, and patient-reported outcomes and quality of life.<\/p>\n
Between February 2020 and August 2022, 168 patients were enrolled at 75 sites. The median age was 66 years (range, 41-85), 76.8% of patients were White, 62.5% had stage IB disease, 17.3% had stage II disease, 48.8% had grade 2 tumors, 33.3% had grade 3 tumors, 57.5% had LVSI-positive disease, and 70.2% received vaginal brachytherapy alone. In the combination arm, 59.8% of patients completed treatment and 40.2% discontinued, including 23 patients who discontinued due to adverse effects (AEs); in the radiation-alone arm, 94.6% of patients completed treatment.<\/p>\n
What did secondary end point data show?<\/p>\n
At the August 27, 2026, data cutoff, with a median follow-up of 53.8 months, 21% of patients in the radiation-alone arm and 14% of patients in the combination arm had experienced recurrence or death. The RFS rates beyond 3 years were 81% and 88%, respectively (log-rank P = .113), and the Cox proportional hazards model yielded an HR of 0.632 (95% CI, 0.299-1.337; P = .115). OS data were not mature, with 9 events reported to date: 4 in the radiation-alone arm and 5 in the combination arm.<\/p>\n
Because the number of patients with unknown 3-year status was relatively large and unbalanced between arms, investigators conducted a sensitivity analysis. Assuming the probability of success among unknown patients in the pembrolizumab arm ranged from 80% to 95%, with the radiation-alone arm held at 80%, the probability of reversing the study’s conclusion ranged from 6.9% to 23%.<\/p>\n
What was the safety profile of the combination?<\/p>\n
In the safety population (radiation alone, n = 53; combination, n = 111), the most common treatment-emergent AEs in the combination arm vs the radiation-alone arm included fatigue (57.7% vs 35.8%), diarrhea (45.0% vs 39.6%), maculopapular rash (32.4% vs 3.8%), hypertension (25.2% vs 15.1%), decreased lymphocyte count (25.2% vs 3.8%), pruritus (23.4% vs 0%), and hypothyroidism (16.2% vs 0%). Grade 3 or higher differences were driven mostly by grade 3 lymphopenia and hypertension; grade 3\/4 decreased lymphocyte count occurred in 15.3% of patients in the combination arm, and grade 3\/4 hypertension occurred in 11.7% vs 7.5% of patients, respectively.<\/p>\n
Most immune-related AEs were grade 1 or 2. Grade 3\/4 immune-related AEs in the combination arm included adrenal insufficiency (3.6%), maculopapular rash (1.8%), and hypophysitis (0.9%), as well as low rates of colitis and pancreatitis.<\/p>\n
Backes noted that the high rate of failures for reasons other than recurrence, the relatively low overall event rate, and the limited sample size were limitations of the study. “There was a relatively low event rate, in total 13% [at] 3 years, with a limited sample size that reduced the ability to detect treatment differences when adding pembrolizumab to radiation,” she said.<\/p>\n
ReferencesBackes FJ, et al. NRG-GY020: phase III randomized trial of radiation +\/- MK-3475 (pembrolizumab) for newly diagnosed early-stage high intermediate risk (HIR) mismatch repair deficient (dMMR) endometrioid endometrial cancer (EC). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 1239O.Van Gorp T, Cibula D, Lv W, et al. ENGOT-en11\/GOG-3053\/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol. 2024;35(11):968-980. doi:10.1016\/j.annonc.2024.08.2242 <\/p>\n","protected":false},"excerpt":{"rendered":"Ahead of the meeting, the trial was noted for restricting enrollment to patients with dMMR disease, in contrast…\n","protected":false},"author":2,"featured_media":655992,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46],"class_list":["post-655991","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/655991","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=655991"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/655991\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/655992"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=655991"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=655991"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=655991"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}