CLINICAL TRIAL UPDATES: Head and Neck Cancer

Long-Term Follow-Up of E3311, an ECOG-ACRIN Cancer Research Group Phase II Trial of Transoral Surgery and Risk-Based Adjuvant Treatment in Human Papillomavirus–Initiated Oropharynx Cancer

  • Burtness, Barbara MD1,,
  • Flamand, Yael MS2
  • Quon, Harry MD3,
  • Weinstein, Gregory S. MD4,
  • Mehra, Ranee MD5,
  • Garcia, Joaquin J. MD6
  • Kim, Seungwon MD7
  • O'Malley, Bert W. Jr MD8,
  • Ozer, Enver MD9
  • Ikpeazu, Chukwuemeka MD, PhD10,
  • Koch, Wayne M. MD11
  • Gross, Neil D. MD12,
  • Bell, R. Bryan MD13,
  • Patel, Mihir MD14,
  • Lango, Miriam N. MD12
  • Morris, Luc G. MD15,
  • Smith, Russell MD16
  • Karakla, Daniel MD17
  • Richmon, Jeremy D. MD18,
  • Holsinger, Floyd C. MD19,
  • Ferris, Robert L. MD, PhD20,

  • 1

    Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT

  • 2

    ECOG-ACRIN Biostatistics Center, Dana-Farber Cancer Institute, Boston, MA

  • 3

    Department of Radiation Oncology and Molecular Radiation Sciences. Johns Hopkins University School of Medicine, Baltimore, MD

  • 4

    Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA

  • 5

    Department of Medicine, University of Maryland Greenebaum Comprehensive Cancer Center

  • 6

    Department of Pathology, Mayo Clinic, Rochester, MN

  • 7

    Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA

  • 8

    The University of Maryland Medical Center, Baltimore, MD

  • 9

    Department of Otolaryngology—Head and Neck Surgery, Ohio State University School of Medicine, Columbus, OH

  • 10

    Department of Medicine, University of Miami School of Medicine, Miami, FL

  • 11

    Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD

  • 12

    Department of Head and Neck Surgery, M. D. Anderson Cancer Center, Houston, TX

  • 13

    Division of Surgical Oncology, Providence Cancer Institute, Portland, OR

  • 14

    Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA

  • 15

    Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

  • 16

    Department of Otolaryngology—Head and Neck Surgery, University of Nebraska Medical Center, Omaha, NE

  • 17

    Department of Otolaryngology—Head and Neck Surgery, Sentara Norfolk General Hospital, Norfolk, VA

  • 18

    Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear Hospital, Harvard Medical School, Boston, MA

  • 19

    Department of Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA

  • 20

    Lineberger Cancer Center and Department of Otolaryngology, University of North Carolina, Chapel Hill, NC
Barbara Burtness, MD; e-mail: [email protected].

*

B.B. and R.L.F. contributed equally to this work.

Journal of Clinical Oncology 43(23):p 2559-2565, August 10, 2025. | DOI: 10.1200/JCO-24-02550

This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)–associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.6% (90% CI, 87.2% to 93.1%) and 95.3% (93.0% to 96.9%), respectively. The 54-month PFS by arm was A 93.2% (79.6% to 97.8%; all four recurrences among N1 patients), B 94.9% (89.7% to 97.5%), C 90.2% (82.7% to 94.6%), and D 85.5% (77.5% to 90.8%). The 54-month OS by arm was A 97.1% (85.7% to 99.4%), B 97.9% (93.5% to 99.3%), C 95.1% (90.1% to 97.6%), and D 92.5% (86.9% to 95.7%). PFS or OS did not differ by primary site or smoking history. TOS and neck dissection with deintensified postoperative management results in outstanding 54-month PFS and OS. Among patients with favorable pathologic characteristics, those with N1 disease are at risk of late recurrence without radiation.

Copyright © 2025 by American Society of Clinical Oncology