Window Studies in Squamous Cell Carcinoma of the Head and Neck: Values and Limits
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In head and neck cancer, we continue to work towards a more personalized approach to treatment of patients, where analysis of a patient’s tumor guides targeting of molecular or immunologic pathways. Critically important to this pursuit is a better understanding of the direct biologic effect of a drug or combination on the tumor microenvironment in humans, as well as biomarker discovery. These goals are consistent with the primary purpose of a “window of opportunity” trial and while conduct of these trials requires a careful balance of benefits and potential risks, to date these trials have been both feasible and safe in HNSCC in the curative intent setting. In the era of immunotherapy, with countless possible combinations and ongoing clinical trials, window trials are even more important for informing clinical trial design and appropriate combination therapy, and ultimately a more personalized approach to our patients that leads to improvement in outcomes.
KeywordsWindow trial HNSCC Neoadjuvant Anti-PD-1 Immunotherapy Targeted therapy Cetuximab
Compliance with Ethical Standards
Conflict of Interest
Dan P. Zandberg has received research support for role as PI for clinical trials conducted by Merck, Bristol-Myers Squibb, and AstraZeneca.
Robert L. Ferris has received research funding for clinical trials conducted by AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck, Tesaro, and VentiRx Pharmaceuticals, and has served on advisory boards for Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, EMD Serono, PPD, Lilly, Merck, Pfizer, and Tesaro.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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- 20.Ferris RL, Goncalves A, Baxi S, UM Martins, Gauthier H, Langenberg M, et al. LBA46—an open-label, multicohort, phase 1/2 study in patients with virus-associated cancers (CheckMate 358): safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck. Ann Oncol. 2017;28(suppl_5):ESMO 2017 Congress.Google Scholar
- 21.R Uppaluri, Zolkind P, Lin T, Nussenbaum B, Jackson R, Rich J, et al. Neoadjuvant pembrolizumab in surgically resectable, HPV negative, locally advanced head and neck squamous cell carcinoma (HNSCC). J Clin Oncol 35, 2017 (Suppl; abstr 6012) ASCO Annual Meeting 2017. 2017.Google Scholar
- 22.•• Bell R, Duhen R, Leidner R, Curti B, Ballesteros-Merino C, Piening B, et al. Neoadjuvant anti-OX40 (MEDI6469) prior to surgery in head and neck squamous cell carcinoma. J Clin Oncol 36, 2018 (suppl; abstr 6011). Oral abstract presentation at ASCO 2018 Annual Meeting. 2018. Important thorough window trial with a newer checkpoint inhibitor.Google Scholar
- 23.Colevas AD, Bedi K, Chang S, Nieves U, Chatterjee S, Davidzon A, et al. A study to evaluate immunological response to PD-1 inhibition in squamous cell carcinoma of the head and neck (SCCHN) using novel PET imaging with [18F]F-AraG. J Clin Oncol 36, 2018 (suppl; abstr 6050) ASCO 2018 Annual Meeting Poster Presentation. 2018.Google Scholar
- 26.Ferris RL, Lenz HJ, Trotta AM, Garcia-Foncillas J, Schulten J, Audhuy F, et al. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. Cancer Treat Rev. 2017;63:48–60.CrossRefGoogle Scholar
- 28.•• Shayan G, Kansy BA, Gibson SP, Srivastava RM, Bryan JK, Bauman JE, et al. Phase Ib study of immune biomarker modulation with neoadjuvant cetuximab and TLR8 stimulation in head and neck cancer to overcome suppressive myeloid signals. Clin Cancer Res. 2018;24(1):62–72. Important combination immunotherapy window trial.CrossRefGoogle Scholar
- 32.Postel-Vinay S, Collette L, Paoletti X, Rizzo E, Massard C, Olmos D, et al. Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents—Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted Therapies, an European Organization for Research and Treatment of Cancer-led study. Eur J Cancer. 2014;50(12):2040–9.CrossRefGoogle Scholar
- 34.Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16(5):583–94.CrossRefGoogle Scholar