Trial reportCancer2022
A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability.
Trial report in Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02899793 (A Phase II Evaluation of Pembrolizumab, a Humanized Antibody Against PD-1, in the Treatment of Persistent or Recurrent Hypermutated/Ultramutated Endometrial Cancer Identified by Next Generation Sequencing), which is not on this map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Evaluation of Pembrolizumab, a Humanized Antibody Against PD-1, in the Treatment of Persistent or Recurrent Hypermutated/Ultramutated Endometrial Cancer Identified by Next Generation Sequencing (NGS) and Comprehensive Genomic Profiling (CGP)
Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
- Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.Nature medicine · 2024Trial
- Clinical utility of diagnosing Lynch syndrome in gynecologic oncology: a joint statement from four Japanese academic societies.International journal of clinical oncology · 2026Review
- Review
- RecQ DNA helicases germline variants in Lynch-like syndrome.Genetics in medicine open · 2026Article
- An intriguing journey into the hereditary syndromes predisposing to endometrial cancer: more than believed.Therapeutic advances in medical oncology · 2026Review
- Predictive biomarkers of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.Therapeutic advances in medical oncology · 2026Review
- A New Direction in Endometrial Cancer Therapy-PD-1 and PD-L1 Immune Checkpoint Inhibitors-Where Will It Take Us?Journal of clinical medicine · 2025Review
- Molecular Prognosticators Guiding Fertility-Sparing Surgery in Early-Stage Endometrial Cancer: A Comprehensive Review.Cancers · 2025Review
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Therapeutic Indications of Pembrolizumab in Eight Common Cancers: Current Evidence and Future Directions.Cancer reports (Hoboken, N.J.) · 2025Review
- Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers.Nature reviews. Clinical oncology · 2025Review
- The Clinical Outcomes Among Patients Under 60 Years Old with Lynch Syndrome: Variations Based on Different Mutation Patterns.International journal of molecular sciences · 2025Review
- Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel.Journal of surgical oncology · 2025Article
- Comprehensive Review of Endometrial Cancer: New Molecular and FIGO Classification and Recent Treatment Changes.Journal of clinical medicine · 2025Review
- Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings.NPJ precision oncology · 2025Article
- Mutation profile and molecular heterogeneity in mismatch repair deficient endometrial carcinoma.Frontiers in oncology · 2025Article
- Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.Journal of gynecologic oncology · 2024Article
- Translating biological insights into improved management of endometrial cancer.Nature reviews. Clinical oncology · 2024Review
- Review
Corrections and comments
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Authors and funding
33 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundMicrosatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) is a biomarker for responses to immune checkpoint inhibitors (ICIs). Whether mechanisms underlying microsatellite instability alter responses to ICIs is unclear. This article reports data from a prospective phase 2 pilot study of pembrolizumab in patients with recurrent MSI-H endometrial cancer (EC) analyzed by whole exome sequencing (WES) and potential mechanisms of primary/secondary ICI resistance (NCT02899793).
methodsPatients with measurable MSI-H/dMMR EC confirmed by polymerase chain reaction/immunohistochemistry were evaluated by WES and received 200 mg of pembrolizumab every 3 weeks for ≤2 years. The primary end point was the objective response rate (ORR). Secondary end points included progression-free survival (PFS) and overall survival (OS).
resultsTwenty-five patients (24 evaluable) were treated. Six patients (25%) harbored Lynch/Lynch-like tumors, whereas 18 (75%) had sporadic EC. The tumor mutation burden was higher in Lynch-like tumors (median, 2939 mutations/megabase [Mut/Mb]; interquartile range [IQR], 867-5108 Mut/Mb) than sporadic tumors (median, 604 Mut/Mb; IQR, 411-798 Mut/Mb; P = .0076). The ORR was 100% in Lynch/Lynch-like patients but only 44% in sporadic patients (P = .024). The 3-year PFS and OS proportions were 100% versus 30% (P = .017) and 100% versus 43% (P = .043), respectively.
conclusionsThis study suggests prognostic significance of Lynch-like cancers versus sporadic MSI-H/dMMR ECs for ORR, PFS, and OS when patients are treated with pembrolizumab. Larger confirmatory studies in ECs and other MSI-H/dMMR tumors are necessary. Defective antigen processing/presentation and deranged induction in interferon responses serve as mechanisms of resistance in sporadic MSI-H ECs. Oligoprogression in MSI-H/dMMR patients appears salvageable with surgical resection and/or local treatment and the continuation of pembrolizumab off study. Clinical studies evaluating separate MSI-H/dMMR EC subtypes treated with ICIs are warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.