Bhumsuk Keam, MD, PhD1,2; Min Hee Hong, MD3; Seong Hoon Shin, MD, PhD4; Seong Gu Heo, PhD5,6; Ji Eun Kim, MD, PhD7; Hee Kyung Ahn, MD, PhD8; Yun-Gyoo Lee, MD, PhD9; Keon-Uk Park, MD, PhD10; Tak Yun, MD, PhD11; Keun-Wook Lee, MD, PhD12; Sung-Bae Kim, MD, PhD13; Sang-Cheol Lee, MD, PhD14; Min Kyoung Kim, MD, PhD15; Sang Hee Cho, MD, PhD16; So Yeon Oh, MD, PhD17; Sang-Gon Park, MD, PhD18; Shinwon Hwang, MD19,20; Byung-Ho Nam, PhD21; Sangwoo Kim, PhD22; Hye Ryun Kim, MD, PhD3; and Hwan Jung Yun, MD23; on behalf of KCSG TRIUMPH Investigators
1Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
3Divison of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
4Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea
5Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
6Division of Cancer Data Science, National Cancer Center, Goyang, Republic of Korea
7Department of Pathology, Seoul National University College of Medicine, SMG-SNU Boramae Hospital, Seoul, Republic of Korea
8Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
9Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
10Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, Republic of Korea
11Rare Cancers Clinic, Center for Specific Organs Cancer, National Cancer Center, Goyang, Republic of Korea
12Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
13Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
14Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
15Division of Hematology-Oncology, Department of Internal Medicine, Yeungnam University Hospital, Yeungnam University College of Medicine, Daegu, Republic of Korea
16Department of Hemato-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea
17Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea
18Department of Hemato-Oncology, Chosun University Hospital, Gwangju, Republic of Korea
19Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
20Department of Medicine, Physician-Scientist Program, Yonsei University College of Medicine, Seoul, Republic of Korea
21HERINGS, Seoul, Republic of Korea
22Department of Biomedical Systems Informatics, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
23Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
*S.K., H.R.K., and H.J.Y. contributed equally to this work.
Corresponding author : Hwan Jung Yun, MD
Purpose: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC.
Methods: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclinb, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment.
Results: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths.
Conclusion: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.