{
  "abstract": "Background In Study 309/KEYNOTE-775 ( NCT03517449), lenvatinib+pembrolizumab versus chemotherapy significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in advanced endometrial cancer (EC). We report 5-year follow-up results.Methods Participants had advanced/recurrent/metastatic EC with progressive disease after one prior platinum-based chemotherapy regimen, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and no prior receipt of anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 agents. Participants were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for ≤35 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included ORR per RECIST v1.1 by BICR and safety. Efficacy endpoints were analyzed using Cox regression, Kaplan-Meier, and Miettinen and Nurminen methodology.Results 827 participants were randomized. At data cut-off (February 26, 2025), overall median follow-up was 68.8 months; 139 participants were alive (lenvatinib+pembrolizumab, n=86; chemotherapy, n=53), and all had ended their treatment in this study. Five-year OS rate was 16.7% with lenvatinib+pembrolizumab versus 7.3% with chemotherapy in mismatch repair-proficient EC, 36.5% versus 9.8% in mismatch repair-deficient EC, and 19.9% versus 7.7% in all-comers. Five-year PFS rates were 6.3% versus 2.1%, 26.4% versus 10.8%, and 9.8% versus 3.2%, respectively. In all-comers, treatment-related adverse events led to any treatment discontinuation in 32.3% versus 5.9%. Subsequent systemic anticancer therapy was used by 44.8% versus 51.2% (lenvatinib+pembrolizumab by 2.4% vs 10.1%).Conclusions Results were consistent with the primary analysis despite increased use of subsequent systemic anticancer therapy and crossover to lenvatinib+pembrolizumab in the chemotherapy group. The continued durable benefit, including OS, with lenvatinib+pembrolizumab and no new safety signals lend further support for this regimen as a standard of care therapy for EC.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Vicky Makker"
    },
    {
      "affiliations": [
        "Gynecologic Oncology Program, European Institute of Oncology, IRCSS, Milan, Italy",
        "Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy",
        "Mario Negri Gynecologic Oncology (MaNGO), Milan, Italy"
      ],
      "name": "Nicoletta Colombo"
    },
    {
      "affiliations": [
        "Medical Oncology Department, Hospital Clinico Universitario San Carlos, Madrid, Spain"
      ],
      "name": "Antonio Casado"
    },
    {
      "affiliations": [
        "Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA"
      ],
      "name": "Alessandro D Santin"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France"
      ],
      "name": "Emeline Colomba"
    },
    {
      "affiliations": [
        "Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"
      ],
      "name": "David S Miller"
    },
    {
      "affiliations": [
        "Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan"
      ],
      "name": "Keiichi Fujiwara"
    },
    {
      "affiliations": [
        "Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy",
        "Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Rome, Italy"
      ],
      "name": "Sandro Pignata"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, National Cancer Center Hospital, Chuo-ku, Japan"
      ],
      "name": "Kan Yonemori"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea"
      ],
      "name": "Yong Man Kim"
    },
    {
      "affiliations": [
        "Medical Oncology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia"
      ],
      "name": "Sally Baron-Hay"
    },
    {
      "affiliations": [
        "Medical Oncology Department, Centre Léon Bérard, University Claude Bernard, GINECO Group, Lyon, France"
      ],
      "name": "Isabelle Ray-Coquard"
    },
    {
      "affiliations": [
        "The Ella Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel"
      ],
      "name": "Ronnie Shapira-Frommer"
    },
    {
      "affiliations": [
        "Department of Oncology, Guy's and St Thomas’ NHS Foundation Trust and King’s College London, London, UK"
      ],
      "name": "Rebecca Kristeleit"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Kurume University, Fukuoka, Japan"
      ],
      "name": "Shin Nishio"
    },
    {
      "affiliations": [
        "Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Aichi, Japan"
      ],
      "name": "Shiro Suzuki"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain"
      ],
      "name": "Eva M Guerra Alía"
    },
    {
      "affiliations": [
        "Individualized Medicine Application and Research Center and Department of Medical Oncology, Ege University, Izmir, Turkey"
      ],
      "name": "Ulus A Sanli"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Groupe hospitalier Diaconesses Croix Saint-Simon and GINECO French group, Paris, France"
      ],
      "name": "Frederic Selle"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan"
      ],
      "name": "Ayumi Shikama"
    },
    {
      "affiliations": [
        "Filios Alta Medicina SA de CV, Monterrey NL, Mexico"
      ],
      "name": "Jorge L Martínez Rodríguez"
    },
    {
      "affiliations": [
        "Hacettepe University Medical Faculty, Ankara, Turkey"
      ],
      "name": "Zafer Arik"
    },
    {
      "affiliations": [
        "Acibadem University Hospital Atakent, Istanbul, Turkey"
      ],
      "name": "Ali Arican"
    },
    {
      "affiliations": [
        "Gynecologic Oncology Division, CHU de Québec-Université Laval, Québec, Québec, Canada"
      ],
      "name": "Alexandra Sebastianelli"
    },
    {
      "affiliations": [
        "Biostatistics and Research Decision Sciences, Merck & Co., Inc, Rahway, New Jersey, USA"
      ],
      "name": "Zhou Yu"
    },
    {
      "affiliations": [
        "Clinical Development Oncology, Eisai Inc, Nutley, New Jersey, USA"
      ],
      "name": "Jodi McKenzie"
    },
    {
      "affiliations": [
        "Global Clinical Development, Merck & Co., Inc, Rahway, New Jersey, USA"
      ],
      "name": "Stephan Kruger"
    },
    {
      "affiliations": [
        "Global Clinical Development, Merck & Co., Inc, Rahway, New Jersey, USA"
      ],
      "name": "Robin Meng"
    },
    {
      "affiliations": [
        "Clinical Development Oncology, Eisai Ltd, Hatfield, UK"
      ],
      "name": "Chinyere E Okpara"
    },
    {
      "affiliations": [
        "Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy",
        "Gynaecological Oncology Medical Unit, Humanitas San Pio X Hospital, Milan, Italy"
      ],
      "name": "Domenica Lorusso"
    }
  ],
  "title": "Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775",
  "uid": "ec983323-54b8-5a21-9539-ccf098a893a0"
}