Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Prospective assessment of the clinical benefit of a tailored cancer gene set built on a next-generation sequencing platform in patients with recurrent or metastatic head and neck cancer

Abstract

We performed a prospective trial to assess the clinical benefit of a tailored gene set built on a next-generation sequencing (NGS) platform in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Archived tumor tissue obtained from patients with recurrent or metastatic HNSCC was analyzed for variants by a tailored Comprehensive Cancer Gene set of 40 genes (CCG-40) performed on a NGS platform. These data were provided to clinicians to inform treatment decisions. The primary endpoint was clinical benefit (disease control) that resulted from selection and administration of a targeted therapy based on results of the CCG-40. Barriers to performance and implementation of the assay were recorded. Forty patients enrolled. Primary tumor sites included oropharynx (14), larynx/hypopharynx (14), oral cavity (9), and nasopharynx (3). The CCG-40 assay was performed in 23 patients (57.5%), but not in 17 patients due inadequate financial coverage (12) or insufficient tumor tissue (5). Potentially actionable tumor variants were identified in 3 patients (7.5%); all were PIK3CA variants. Due to inability to obtain access to candidate drugs (2) or rapid decline in performance status (1), none of these patients received targeted therapy informed by the CCG-40 results. The CCG-40 assay did not provide clinical benefit to the patients on this trial. Identification of limitations of the assay and barriers to the test’s performance and application may be used to optimize this strategy in future trials.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Ford J. Precision oncology: a new forum for an emerging field. JCO Precis Oncol. 2017;1(1):1–2.

  2. 2.

    Tsimberidou AM, Iskander NG, Hong DS, et al. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res. 2012;18(22):6373–83.

  3. 3.

    Slamon DJ, Leyland-jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

  4. 4.

    Van de Vijver MJ, He YD, Van’t veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.

  5. 5.

    Mcarthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15(3):323–32.

  6. 6.

    Agrawal N, Frederick MJ, Pickering CR, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333(6046):1154–7.

  7. 7.

    Pickering CR, Zhang J, Yoo SY, et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 2013;3(7):770–81.

  8. 8.

    Lui VW, Hedberg ML, Li H, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;3(7):761–9.

  9. 9.

    Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–60.

  10. 10.

    Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82.

  11. 11.

    Seiwert TY, Zuo Z, Keck MK, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21(3):632–41.

  12. 12.

    Hedberg ML, Goh G, Chiosea SI, et al. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma. J Clin Invest. 2016;126(1):169–80.

  13. 13.

    Morris LG, Chandramohan R, West L, et al. The molecular landscape of recurrent and metastatic head and neck cancers: insights from a precision oncology sequencing platform. JAMA Oncol. 2017;3(2):244–55.

  14. 14.

    Chung CH, Guthrie VB, Masica DL, et al. Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol. 2015;26(6):1216–23.

  15. 15.

    Chau NG, Li YY, Jo VY, et al. Incorporation of next-generation sequencing into routine clinical care to direct treatment of head and neck squamous cell carcinoma. Clin Cancer Res. 2016;22(12):2939–49.

  16. 16.

    Tinhofer I, Budach V, Saki M, et al. Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation. Eur J Cancer. 2016;57:78–86.

  17. 17.

    Hagemann IS, Devarakonda S, Lockwood CM, et al. Clinical next-generation sequencing in patients with non-small cell lung cancer. Cancer. 2015;121(4):631–9.

  18. 18.

    National Center for Biotechnology Information. dbSNP. http://www.ncbi.nlm.nih.gov/projects/SNP/Accessed 19 Jan 2019.

  19. 19.

    1000 Genomes. http://www.1000genomes.org. Accessed 19 Jan 2019.

  20. 20.

    NHLBI Exome Sequencing Project. Exome Variant Server. https://evs.gs.washington.edu/. Accessed 19 Jan 2019.

  21. 21.

    Catalogue of Somatic Mutations in Cancer. http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/. Accessed 19 Jan 2019.

  22. 22.

    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

  23. 23.

    Cohen EEW, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156–67.

  24. 24.

    Burtness B, Harrington KJ, Greil R, et al. KEYNOTE-048: phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma. Abstract presented at ESMO 2018 Congress; 2018 October 22; Munich.

  25. 25.

    Meric-bernstam F, Brusco L, Shaw K, et al. Feasibility of large-scale genomic testing to facilitate enrollment onto genomically matched clinical trials. J Clin Oncol. 2015;33(25):2753–62.

  26. 26.

    Massard C, Michiels S, Ferté C, et al. High-Throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017;7(6):586–95.

  27. 27.

    Rodon J, Soria JC, Berger R, et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat Med. 2019;25(5):751–8.

  28. 28.

    Sicklick JK, Kato S, Okamura R, et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. 2019;25(5):744–50.

  29. 29.

    Schwaederle M, Zhao M, Lee JJ, et al. Impact of precision medicine in diverse cancers: a meta-analysis of phase II clinical trials. J Clin Oncol. 2015;33(32):3817–25.

  30. 30.

    Lim SM, Cho SH, Hwang IG, et al. Investigating the feasibility of targeted next-generation sequencing to guide the treatment of head and neck squamous cell carcinoma. Cancer Res Treat. 2019;51(1):300–12.

  31. 31.

    Le Tourneau C, Delord JP, Gonçalves A, et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015;16(13):1324–34.

Download references

Acknowledgements

We recognize the support of the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri. The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant P#30 CA91842.

Author information

Correspondence to Douglas Adkins.

Ethics declarations

Conflict of interest

All authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 704 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Westbrook, T.C., Hagemann, I.S., Ley, J. et al. Prospective assessment of the clinical benefit of a tailored cancer gene set built on a next-generation sequencing platform in patients with recurrent or metastatic head and neck cancer. Med Oncol 37, 12 (2020). https://doi.org/10.1007/s12032-019-1336-3

Download citation

Keywords

  • Head and neck cancer
  • Metastasis
  • Precision medicine