Personalized biomarker-based treatment strategy in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: Results of the biomarker-driven cohorts of the EORTC-HNCG-1559 trial (UPSTREAM).

Galot, Rachel;Le Tourneau, Christophe;Licitra, Lisa;Guigay, Joel;Machiels, Jean-Pascal;et.al.
(2025) 2025 ASCO Annual Meeting I (2025)

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Authors
  • Galot, RachelUCLouvain
    Author
  • Le Tourneau, ChristopheDepartment of Drug Development and Innovation (D3i), Institut Curie, Paris-Saclay University, Paris, France
    Author
  • Licitra, LisaFondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
    Author
  • Guigay, JoelCentreAntoineLacassagne, Nice, France
    Author
  • Seront, EmmanuelUCLouvain
    Author
  • Machiels, Jean-PascalUCLouvain
    Author
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Abstract
Background: Platinum-refractory recurrent/metastatic squamous cell carcinoma (R/M SCCHN) has a poor prognosis. Several molecular pathways are dysregulated in SCCHN, providing potential targets for treatment. The UPSTREAM trial aimed to develop a personalized treatment strategy for R/M SCCHN. Methods: UPSTREAM was a biomarker-driven umbrella trial for post-platinum R/M SCCHN, investigating the activity of targeted agents in patients (pts) with tumors harboring pre-defined biomarker(s) identified on a fresh biopsy. Five biomarker-driven (B) cohorts were conducted as distinct phase 2 trials. The first 4 cohorts focused on p16-negative disease: cohort B1 investigated afatinib in pts with EGFR amp/mut and/or HER2 amp/mut and/or PTEN high; cohort B2 investigated afatinib in cetuximab-naïve pts; cohort B3 investigated palbociclib in pts with CCND1 amp and cohort B4 investigated niraparib in platinum-sensitive disease. Cohort B5 investigated niraparib in p16 positive oropharyngeal carcinoma. Cohorts B1, B2 and B3 were randomized (versus physician's choice of treatment) with progression-free survival rate at 16 weeks (PFSR 16W) as primary endpoint. Cohorts B4 and B5 were single-arm trials with objective response rate (ORR) over the first 16 weeks as primary endpoint. Results: A total of 250 pts were enrolled in UPSTREAM across 5 European countries, of whom 152 were allocated to a biomarker-driven cohort. Only B1 met its primary endpoint. In B1 (n=38 under afatinib), the PFSR 16W was 34.2%. B2 cohort experienced slow recruitment, with only 8 patients treated with afatinib, the PFSR 16W was 12.5%. In B3 (n=12 under palbociclib), PFSW 16W was 16.7%. In B4 (n=28) and B5 (n= 33), the ORR with niraparib was 3.6% (1/28) and 6.1% (2/33), respectively. More detailed results are shown in the table. Conclusions: UPSTREAM demonstrated the feasibility of conducting a biomarker-driven clinical trial in R/M SCCHN. The clinical activity observed across the biomarker-driven cohorts is limited. Potential explanations for these results include the absence of clearly identified high-level drivers in SCCHN, the limited evidence supporting some biomarkers (mainly derived from genomic data), and the use of single-agent treatment approaches. These findings highlight the need for further research to identify and refine biomarkers to explore new treatment strategies. Clinical trial information: NCT03088059. Research Sponsor: Boehringer Ingelheim; Pfizer; GSK.
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Galot, R., Le Tourneau, C., Licitra, L., Guigay, J., Kong, A., Tinhofer, I., Even, C., Daste, A., Saada-Bouzid, E., Rolland, F., Henry, S., Rottey, S., Seront, E., Rutten, A., Debruyne, P., Tsechilidou, K., Fortpied, C., Joaquim, A., Govaerts, A.-S., & Machiels, J.-P. (2025). Personalized biomarker-based treatment strategy in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: Results of the biomarker-driven cohorts of the EORTC-HNCG-1559 trial (UPSTREAM). Journal of Clinical Oncology, 43(16_suppl), 6028. https://doi.org/10.1200/jco.2025.43.16_suppl.6028 (Original work published 2025)