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A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.
Kim, Chang Gon; Hong, Min Hee; Kim, Dahee; Lee, Brian Hyohyoung; Kim, Hyunwook; Ock, Chan-Young; Kelly, Geoffrey; Bang, Yoon Ji; Kim, Gamin; Lee, Jung Eun; Kim, Chaeyeon; Kim, Se-Heon; Hong, Hyun Jun; Park, Young Min; Sim, Nam Suk; Park, Heejung; Park, Jin Woo; Lee, Chang Geol; Kim, Kyung Hwan; Park, Goeun; Jung, Inkyung; Han, Dawoon; Kim, Jong Hoon; Cha, Junha; Lee, Insuk; Kang, Mingu; Song, Heon; Oum, Chiyoon; Kim, Seulki; Kim, Sukjun; Lim, Yoojoo; Kim-Schulze, Seunghee; Merad, Miriam; Yoon, Sun Och; Kim, Hyun Je; Koh, Yoon Woo; Kim, Hye Ryun.
Afiliação
  • Kim CG; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Hong MH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim D; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Lee BH; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Kim H; Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Ock CY; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kelly G; Lunit Inc., Seoul, Republic of Korea.
  • Bang YJ; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Kim G; Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Lee JE; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim C; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim SH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Hong HJ; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Park YM; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Sim NS; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Park H; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Park JW; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Lee CG; Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim KH; Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Park G; Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Jung I; Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Han D; Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Kim JH; Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Cha J; Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Lee I; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
  • Kang M; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
  • Song H; Lunit Inc., Seoul, Republic of Korea.
  • Oum C; Lunit Inc., Seoul, Republic of Korea.
  • Kim S; Lunit Inc., Seoul, Republic of Korea.
  • Kim S; Lunit Inc., Seoul, Republic of Korea.
  • Lim Y; Lunit Inc., Seoul, Republic of Korea.
  • Kim-Schulze S; Lunit Inc., Seoul, Republic of Korea.
  • Merad M; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Yoon SO; Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Kim HJ; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Koh YW; Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Kim HR; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Clin Cancer Res ; 30(10): 2097-2110, 2024 May 15.
Article em En | MEDLINE | ID: mdl-38457288
ABSTRACT

PURPOSE:

Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND

METHODS:

Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses.

RESULTS:

Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T.

CONCLUSIONS:

Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Terapia Neoadjuvante / Anticorpos Monoclonais Humanizados / Carcinoma de Células Escamosas de Cabeça e Pescoço / Neoplasias de Cabeça e Pescoço / Anticorpos Monoclonais Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Terapia Neoadjuvante / Anticorpos Monoclonais Humanizados / Carcinoma de Células Escamosas de Cabeça e Pescoço / Neoplasias de Cabeça e Pescoço / Anticorpos Monoclonais Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article