As trials mature, patient selection for neoadjuvant immunotherapy will need to be defined further. Preoperative Chemotherapy in Advanced Resectable OCSCC: Long-Term Results of a Randomized Phase III Trial. Clin Cancer Res (2020) 26(13):32119. Lancet (2019) 394(10212):191528. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. Figure1 Representative figure of pathological tumor response (pTR). Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. Ann Oncol (2019) 30(1):4456. Palbociclib in hormone-receptor-positive advanced breast cancer. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. J Clin Oncol. Zuur CL, Elbers JBW, Vos JL, Avd L, Qiao X, Karakullukcu B, et al. To test the sequencing of these therapies in the laryngeal cancer setting, RTOG 91-11 compared the clinical efficacy of 1) IC followed by RT, 2) CCRT and 3) RT alone for advanced laryngeal cancer patients (23). The CD8+ T cell data was correlated with preclinical models, where anti-PD-1 and anti-CTLA4 combinatorial therapy increased tumor-infiltrating CD8+ T cells (71). Induction Chemotherapy in Advanced Head and Neck Tumors. Nivolumab Plus Ipilimumab in Lung Cancer With a High Tumor Mutational Burden. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. BMC Med. J Clin Oncol. RU serves on an advisory board for Merck, Inc. Similarly, the Keynote-040 randomized phase III trial compared the efficacy of pembrolizumab (anti-PD-1) versus SOC (methotrexate, docetaxel, or cetuximab) (13) for R/M HNSCC patients after platinum-containing treatment. These are the first clear data in HNSCC supporting the finding that neoadjuvant anti-PD1 induced PR is a predictor of clinical outcomes. Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect. The TAX 324 trial compared two different induction chemotherapy regimens in patients undergoing chemoradiotherapy, and the PARADIGM and DECIDE trials studied the role of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone. 2016;387(10028):162937. J Clin Oncol (2015) 33(8):83645. Pathologic responses were evaluated in 34 patients (17 HPV+ and 17 HPV-negative). Multi-disciplinary treatments, integrating surgery, chemotherapy, and radiation, aim to maximize treatment effects but have significant functional impact. J Clin Oncol (2003) 21(2):32733. J Clin Oncol (2017) 35(14):15429. Histological Assessment. New Treatment for Head/Neck Tumours | Tissuepathology.com Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. doi: 10.1016/S1470-2045(13)70334-6, 64. PubMedGoogle Scholar, Yajnik, S. (2019). Intriguingly, in preclinical mouse models, a specific interval between neoadjuvant immunotherapy and subsequent surgery was important to establish potent systemic T cell response (33), suggesting that it will be important to establish the optimal duration in the clinical setting. This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology. Remon J, Besse B, Soria JC. He has authored or co-authored over 120 scientific papers in Polish and international journals (with an impact factor of above 1200, index-H: 32, citation index>4000), and is co-author of national and international recommendations for sarcoma and melanoma. Immune Biomarkers of Response to Immune-Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. Oncoimmunology (2019) 8(5):e1581530. Forastiere A, et al. Lancet Oncol. Bossi P, Lo Vullo S, Guzzo M, Mariani L, Granata R, Orlandi E, et al. doi: 10.1038/s41591-020-0805-8, 36. Notably, the treatments were safe and 16/26 patients (61.5%) had pathologic responses (>20%) and 8/26 (31%) of patients experienced complete response (72). J Clin Oncol. The study is aimed at establishing the purpose of tumour markers, their application, classification, diagnostic and therapeutic roles in the management of head and neck cancer. Part of Springer Nature. Compared to our initial cohort with one dose, we found that 50% of patients had any pTR and 44% of patients exhibited pTR2. Lancet Oncol. Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, et al. A Study to Evaluate Fractionated Radiation Therapy Utilizing GRID Therapy for Locally-advanced Bulky Tumors. J Clin Oncol. Article Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. PR is an active member of the EORTC Soft Tissue and Bone Sarcoma Group, where he chaired the Local Treatment Subcommittee and the Membership Committee of the EORTC Board. Any pTR was seen in 44% and pTR-2 was seen in 22% of patients. 2012;366(15):138292. Weissferdt A, Pataer A, Vaporciyan AA, Correa AM, Sepesi B, Moran CA, et al. Head And Neck Cancer - SlideShare There are several questions about how this approach would integrate with current SOC including whether this treatment intensification is necessary especially in good prognosis HPV+ disease and the role of nivolumab as SBRT alone conferred a high rate of pathologic responses. doi: 10.1056/NEJMoa032641, 8. Gillison ML, et al. 2012;31:84552. doi: 10.1200/JCO.2016.70.1524, 45. HNSCC patients with high CD8+ T cells infiltration showed better anti-PD-1 response in the adjuvant setting (52, 54). B Cell Signatures and Tertiary Lymphoid Structures Contribute to Outcome in Head and Neck Squamous Cell Carcinoma. J Clin Oncol (2019) 37(15_suppl):25755. The immunological responses were analyzed using blood before and after treatment. J Clin Oncol. 2016;35:4907. In phase 3 trials, ibrutinib, a first-in-class Bruton tyrosine kinase (BTK) inhibitor, showed efficacy over traditional salvage therapeutic options in patients with relapsed or refractory CLL [32]. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. Notably, other work has contradicted the above studies on TMB and concluded that that high TMB failed to predict the effect of ICI (53). 2023 Springer Nature Switzerland AG. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol (2021) 39(15_suppl):60533. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. The phase II Checkpoint Inhibitors Assessment in Oropharynx cancer (CIAO) trial (NCT03144778) tested a combination of durvalumab (1500 mg) and tremelimumab (75 mg) in the neoadjuvant setting, preceding SOC (surgery with or without radiation therapy) (70). These data indicate that PD-L1 expression on tumor cells is not a perfect biomarker to predict the clinical outcome. Notably, grade 3/4 serious adverse events or delay of surgery didnt occur, underscoring the safety of neoadjuvant immunotherapy. J Radiat Oncol Biol Phys. Head and Neck Cancer | NEJM However, the proportion of CD4+ T cells were decreased while the rate of CD4+FoxP3+ regulatory T cells was increased with treatment. N Engl J Med. Merlino DJ, Johnson JM, Tuluc M, Gargano S, Stapp R, Harshyne L Jr., et al. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in Squamous cell carcinoma (SCC) is the predominant malignant histology of the mucosal surfaces of the head and neck (HN) region that includes the oral cavity, pharynx, and larynx. J Clin Oncol. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Despite this multi-modality treatment, advanced human papillomavirus (HPV)-negative HNSCC shows poor prognosis. CrossRef Platinum-Based Chemotherapy Plus Cetuximab in Head and Neck Cancer. In addition, there was evidence of response in both arms. This is multi-institutional trial enrolled 92 patients and 76 patients were evaluable for DFS. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil CM, Lotem M, Larkin JMG, Lorigan P, Neyns B, Blank CU, Petrella TM, Hamid O, Zhou H, Ebbinghaus S, Ibrahim N, Robert C. Pembrolizumab versus ipilimumab for advanced melanoma: Final overall survival analysis of KEYNOTE-006. She has been an expert advisor for NHS NICE Health Technology Assessments. doi: 10.1200/JCO.2003.06.146, 27. Schoenfeld etal. doi: 10.1056/NEJM199106133242402, 23. Immunological Effects of Nivolumab Immunotherapy in Patients With Oral Cavity Squamous Cell Carcinoma. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. 2016;387(10030):183746. Recent landmark trials in HER2-positive breast cancer include those using dual HER2-targeted therapy pertuzumab and trastuzumab with docetaxel. https://doi.org/10.1186/s12916-017-0884-7, DOI: https://doi.org/10.1186/s12916-017-0884-7. Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. head neck oncology advances.ppt - Google Slides Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F, COMPLEMENT 1 Study Investigators. We also highlight selected and recent practice-changing trials in chronic lymphocytic leukaemia as well as breast and gynaecological cancers, and review the advances offered by the development of novel clinical trial designs. Herbst RS, Baas P, Kim DW, Felip E, Prez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro Jr G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Atezolizumab versus docetaxel for patients with previously treated nonsmall-cell lung cancer (POPLAR): a multicentre, open label, phase 2 randomised controlled trial. . From a clinical standpoint, he is actively involved in the management and treatment of patients with hematological malignancies and, particularly, those suffering from lymphoproliferative disorders. DCruz A, et al. Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. She is co-lead for the Breast Cancer Programme at the Cancer Research UK Cambridge Cancer Centre and significantly contributes to the translational endeavour in precision medicine and the development of personalised treatment pathways in breast cancer. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, et al. Neoadjuvant immunotherapy has the potential to enhance clinical outcomes by increasing anti-tumor immune responses in the presence of abundant tumor-derived antigen in an immune microenvironment that has not been exposed to previous therapy. Novel Strategies to Effectively De-Escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. doi: 10.1038/nature12477, 51. Our doctors are running clinical trials testing: new drug therapies for head and neck cancer, including immunotherapies and targeted therapies, that can boost the effectiveness of your care. Article Impact of Neoadjuvant Durvalumab With or Without Tremelimumab on CD8(+) Tumor Lymphocyte Density, Safety, and Efficacy in Patients With Oropharynx Cancer: CIAO Trial Results. Understanding Patterns of Pathologic Response Following Neoadjuvant Immunotherapy for Solid Tumors. He was/is member of the editorial board of Leukemia and Lymphoma, BMC Medicine, ISRN Hematology and International Journal of Hematologic Oncology. In: Landmark Trials in Oncology. Head and Neck Cancer Clinical Trials and Research - 50.249.249.18. doi: 10.1172/jci.insight.98811, 53. doi: 10.1038/nature12634, 50. Final results of local-regional control and late toxicity of RTOG 90-03; a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Pembrolizumab versus ipilimumab in advanced melanoma. IC resulted in larynx preservation but did not contribute to improved survival. The Checkmate 358 phase I/II study examined clinical safety and efficacy of two doses of neoadjuvant nivolumab in HPV positive or negative HNSCC (NCT02488759) (67). 1. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. The pTR scores were evaluated by two independent pathologists and graded using the following scale: pTR-0 < 10%, pTR-1; 10-49%, pTR-2 50%. Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Corts J, CLEOPATRA Study Group. Privacy 2014;32(12):123641. In a landmark trial, a . N Engl J Med. Park JW, Liu MC, Yee D, Yau C, van t Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA, I-SPY 2 Investigators.