doi: 10.1158/2159-8290.CD-16-0577, 38. Another topic featured in this article collection is systemic therapy in STS [5], which is a heterogeneous group of rare solid tumours. 1. Friedman J, Moore EC, Zolkind P, Robbins Y, Clavijo PE, Sun L, et al. doi: 10.1016/S1470-2045(10)70017-6, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. Matlung SE, Wilhelmina van Kempen PM, Bovenschen N, van Baarle D, Willems SM. Clin Cancer Res (2017) 23(12):315867. Neoadjuvant Immunoradiotherapy Results in High Rate of Complete Pathological Response and Clinical to Pathological Downstaging in Locally Advanced Head and Neck Squamous Cell Carcinoma. Front. 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. CAS doi: 10.1038/s41591-020-01188-3, 65. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The head and neck region is anatomically complex and serves essential functions such as eating, speaking, and breathing. All authors read and approved the final manuscript. The Mutational Landscape of Head and Neck Squamous Cell Carcinoma. PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer. HNSCC patients with high CD8+ T cells infiltration showed better anti-PD-1 response in the adjuvant setting (52, 54). A phase II trial was reported by Xiong etal. 2016;34(8):78693. Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson 3rd WE, Daniels GA, DiMaio D, Ernstoff M, Fields RC, Fleming MD, Gonzalez R, Guild V, Halpern AC, Hodi Jr FS, Joseph RW, Lange JR, Martini MC, Materin MA, Olszanski AJ, Ross MI, Salama AK, Skitzki J, Sosman J, Swetter SM, Tanabe KK, Torres-Roca JF, Trisal V, Urist MM, McMillian N, Melanoma EA. statement and The FOCUS 4 trial in metastatic colorectal cancer uses group-sequential multi-arm, multi-stage methodology [46] to achieve similar matching of novel therapy and biomarker groups. Enhanced Pathologic Tumor Response With Two Cycles of Neoadjuvant Pembrolizumab in Surgically Resectable, Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC). Lancet. In addition to radiation and immunotherapy combinations, other trials are testing chemotherapy/immunotherapy combinations. Spotlight on landmark oncology trials: the latest evidence and novel trial designs, https://doi.org/10.1186/s12916-017-0884-7, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. 2018. Xu Y, Zhu G, Maroun CA, Wu IXY, Huang D, Seiwert TY, et al. Lancet Oncol. Bayesian adaptive designs for biomarker trials with biomarker discovery. Springer Nature. These data show that two doses or the longer neoadjuvant window (3 versus 6 weeks) resulted in an increased rate of pTR but did not increase the total proportion of patients with pTR. Pathological Response and Survival With Neoadjuvant Therapy in Melanoma: A Pooled Analysis From the International Neoadjuvant Melanoma Consortium (INMC). 2006;64(1):4756. This was nearly double what we saw with one dose of pembrolizumab. Hitt R, Grau JJ, Lpez-Pousa A, Berrocal A, Garca-Girn C, Irigoyen A, et al. Therefore, in absence of data from this and similar trials, either therapeutic choice is adequate in the day-to-day practice. Major pathological responses were seen in 1 HPV-positive tumor with none in the HPV-negative tumors. Biomarkers in Head and Neck Cancer an Update - PubMed Redman JM, Gibney GT, Atkins MB. Pignon J-P, et al. HPV infection might also be a clinical biomarker to predict the response to CPIs. Head Neck (2005) 27(10):84350. J Clin Oncol (2013) 31(6):74451. doi: 10.1093/annonc/mdy495, 49. Br J Cancer. Pan-Tumor Genomic Biomarkers for PD-1 Checkpoint Blockade-Based Immunotherapy. HS: writing original draft, tables, and figure. Frameshift Events Predict Anti-PD-1/L1 Response in Head and Neck Cancer. With the advent of novel oral agents that are well tolerated and highly efficacious, the therapeutic landscape of CLL underwent radical changes [31]. N Engl J Med. Google Scholar. Google Scholar. Earl, H., Molica, S. & Rutkowski, P. Spotlight on landmark oncology trials: the latest evidence and novel trial designs. As opposed to the CIAO and IMCISION trials where some patients enrolled were undergoing salvage surgery, a third trial recently presented at ASCO 2021 focused exclusively on challenging recurrent, surgically resectable HNSCC patients (NCT03341936) (73). doi: 10.1126/science.1208130, 12. doi: 10.1016/0360-3016(92)90027-F, 19. His current research is focused on investigating the impact of novel laboratory parameters for assessing prognosis of CLL. Three trials dealing with nasopharynx cancer are discussed including the Intergroup 0099 trial and the MAC-NPC Collaborative Group meta-analysis which studied the role of chemotherapy. Mol Cancer Ther (2017) 16(11):2598608. J Cancer Res Clin Oncol (1997) 123(9):46977. doi: 10.1158/1078-0432.CCR-20-1695, 55. J Clin Oncol. It remains the fifth leading cause of cancer in the United States and constitutes 10% or more of all cancers worldwide. All authors contributed to the article and approved the submitted version. Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, et al. Despite this multi-modality treatment, advanced human papillomavirus (HPV)-negative HNSCC shows poor prognosis. Tumors with both PD-L1 and PD-L2 expression responded better than tumors with only PD-L1 expression, indicating that combinatorial scoring may be an attractive approach. The landmark phase III CheckMate 141 trial resulted in the approval of nivolumab in the R/M second-line HNSCC setting (12). J Clin Oncol. doi: 10.1073/pnas.0915174107, 72. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. Nature (2015) 517(7536):57682. A Randomized Phase III Trial Comparing Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone as Treatment of Unresectable Head and Neck Cancer. doi: 10.1200/JCO.2017.76.2591, 26. Burtness B, Harrington KJ, Greil R, Soulires D, Tahara M, de Castro G Jr, et al. 2012;379:187986. Table1 Completed neoadjuvant immunotherapy clinical trials. Study 19 [28, 29] used olaparib against placebo and demonstrated a PFS of 11.2months in BRCA-mutated patients compared with 4.3months for wild-type patients (hazard ratio, 0.18; P<0.0001). NEngl J Med (2016) 375(19):185667. DCruz A, et al. Epidemiology. reported on findings from a clinical trial where neoadjuvant nivolumab (240 mg on days 1 and 15) with or without tadalafil was tested. elective versus therapeutic neck dissection in node-negative oral cancer. Following this, the phase III KEYNOTE-048 trial established a new paradigm for first-line R/M HNSCC patients (14). Clinical Trials - Head and Neck Cancer Alliance Adaptive randomization of neratinib in early breast cancer. Schffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, DAdamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. https://doi.org/10.1007/978-3-030-14405-0_7, DOI: https://doi.org/10.1007/978-3-030-14405-0_7. Considering the high-frequency of severe adverse events and lack of significant effect OS prolongation with induction chemotherapy, neoadjuvant immunotherapy thus represents an attractive option for advanced HNSCC treatment. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Per standard of care, postoperative RT or CCRT were performed, and adjuvant pembrolizumab treatment was used in high-risk patients with positive surgical margins or extra-nodal extension. Nat Med (2020) 26(4):56676. Science (2011) 333(6046):115760. SM is Chief of the Department Hematology-Oncology at the Azienda Ospedaliera Pugliese-Ciaccio Catanzaro, Italy. In conclusion, neoadjuvant approaches provide a potential exciting new treatment paradigm for HNSCC patients. She is an Editorial Board Member for BMC Medicine. BMC Medicine *Correspondence: Ravindra Uppaluri, Ravindra_Uppaluri@DFCI.Harvard.edu, ORCID: Hirofumi Shibata, orcid.org/0000-0002-7104-9456Ravindra Uppaluri, orcid.org/0000-0001-5988-6828, Immunology and Immunotherapy of Head and Neck Cancer, View all cancer [2], melanoma [3, 4], STS [5], head and neck cancer [6]). Induction Chemotherapy Plus Radiation Compared With Surgery Plus Radiation in Patients With Advanced Laryngeal Cancer. 2016;375(1):1122. Ann Oncol (2019) 30(1):5767. 2017;15(4):50435. Patients with high-TMB have more effective clinical responses with improved survival in lung, bladder, and head and neck cancer patients (47, 48). Part of Springer Nature. Finally, biomarker and minimal residual disease assessment may ultimately be useful to guide the targeted agent or regimen of choice and the duration of treatment [38]. Other work showed that PD-L2 expression was significantly correlated with PD-L1 expression in HNSCC clinical samples (42). BMC Med. The first articles in the special article collection focus on landmark clinical trials in selected advanced solid tumours, with special attention on the most studied tumours with regards to immunotherapy development, namely melanoma [3, 4], NSCLC [], and head and neck cancer [].Recent developments and approvals in immunotherapy have significantly changed the landscape of melanoma and NSCLC . Recent developments and approvals in immunotherapy have significantly changed the landscape of melanoma and NSCLC therapy in the metastatic setting, and open various possibilities for adjuvant treatment in high-risk locoregional disease [7,8,9,10]. PubMed Szturz P, Vermorken JB. Three HPV-positive tumors and one HPV-negative tumor had partial pathologic responses. HNSCC shows a relatively high tumor-mutational burden (TMB) (16) and immune infiltration (17), consistent with a potential to achieve therapeutic efficacy from cancer immunotherapy. In addition to ongoing Phase II trials, KEYNOTE-689 is an international phase III study (NCT03765918) where surgically resectable locally advanced HPV-negative HNSCC patients are randomized to receive upfront surgery with SOC adjuvant treatment or neoadjuvant pembrolizumab (two doses) followed by surgery and SOC adjuvant treatment with pembrolizumab (76). doi: 10.1200/JCO.2019.37.15_suppl.TPS6090, 77. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. Median PFS was 9.5months in the fulvestrant plus palbociclib group and 4.6months in the fulvestrant plus placebo group with a hazard ratio of 0.46, which was highly statistically significant. Lancet Oncol. PD-1 and CTLA-4 Combination Blockade Expands Infiltrating T Cells and Reduces Regulatory T and Myeloid Cells Within B16 Melanoma Tumors. However, cancer research also faces challenges in the effective development and assessment of targeted therapeutics [1], including the need for early evaluation of potential biomarkers by translational and correlative studies. Management of toxicities in this setting remains a challenge. This enhanced function acts to destroy micro-metastasis in clinically advanced tumors, decreasing loco-regional or distant metastasis after primary therapies.
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