Cancer Research and Treatment

Original Articles

Head and Neck cancer

Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Cancer Res Treat. 2025;57(4):968-980. Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195

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Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate, overall survival (OS), and progression-free survival (PFS).
Results
From October 2017 and August 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutation (H1047), patients with H1047 mutation exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutation showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of next-generation sequencing testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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Actualités 2025 par le comité de rédaction du Bulletin du Cancer : congrès ASCO, ESMO et au-delà
Stéphane Vignot, Audrey Bellesoeur, Delphine Borchiellini, Carole Bouleuc, Romain Cohen, Alexandre de Nonneville, Frédéric Delom, Serge Evrard, Nelly Firmin, Virginie Gandemer, Mohamed Khettab, Daniel Orbach, Manuel Rodrigues, Sébastien Thureau, Marie Wis
Bulletin du Cancer.2026; 113(1): 8. CrossRef
Beyond EGFR inhibition in head and neck squamous cell carcinoma: Overcoming resistance mechanisms and novel therapeutic frontiers
Francesca Carosi, Daria Maria Filippini, Laura Fabbri, Andrea Carlini, Andrea Monte, Michela Sgarzi, Matteo Fermi, Giulia Querzoli, Donatella Romaniello, Giuseppe Mercante, Achille Tarsitano, Christophe Le Tourneau, Mattia Lauriola
Critical Reviews in Oncology/Hematology.2026; 221: 105207. CrossRef
Prognostic Biomarkers and Immunotherapeutic Insights of Circulating Tumor DNA Analysis in Advanced Esophageal Squamous Cell Carcinoma From SCRUM-MONSTAR GOZILA Substudy
Yuqing Duan, Tadayoshi Hashimoto, Taro Shibuki, Hiroya Taniguchi, Yu Sunakawa, Yoshito Komatsu, Naoki Takahashi, Yuta Sato, Kensei Yamaguchi, Tomohiro Nishina, Tomonori Nakanoko, Shogen Boku, Taroh Satoh, Hisateru Yasui, Taito Esaki, Mitsuho Imai, Takao F
JCO Precision Oncology.2026;[Epub] CrossRef
Driving progress in recurrent and metastatic head and neck cancer: the NRG Oncology perspective
Mercedes Herrera, Matthew Ward, Glenn J Hanna, Sue S Yom, Dwight Heron, Anna Spreafico
JNCI: Journal of the National Cancer Institute.2026;[Epub] CrossRef
PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás, Marta Pojo
International Journal of Molecular Sciences.2025; 26(11): 5276. CrossRef

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Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy: Eun Joo Kang, Shinwon Hwang, Yun-Gyoo Lee, Jong-Kwon Choi, Seong Hoon Shin, Yoon Hee Choi, Keun-Wook Lee, Hyun Woo Lee, Min Kyoung Kim, Seung Taek Lim, Hwan Jung Yun, Sang-Gon Park, Sangwoo Kim, Sung-Bae Kim, Hye Ryun Kim; Cancer Res Treat. 2025;57(3):709-719. Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836

Abstract PDF PubReader ePub

Purpose
Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).
Results
TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion
TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

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Early-Onset Oral Tongue Squamous Cell Carcinoma in the Absence of Traditional Risk Factors: A Case Report with Whole-Exome Sequencing Analysis
Evgeniy Aleksiev, Darina Lyudmilova Kachakova-Yordanova, Vanyo Mitev, Martin Marinov Georgiev, Zornitsa Mihaylova
Reports.2026; 9(2): 130. CrossRef

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