Details

Autor(en) / Beteiligte

• 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

Titel

A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma

Ist Teil von

• Clinical cancer research, 2024-05, Vol.30 (10), p.2097-2110

Erscheinungsjahr

2024

Beschreibungen/Notizen

• 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.