Head Neck (2005) 27(10):84350. Notably, other work has contradicted the above studies on TMB and concluded that that high TMB failed to predict the effect of ICI (53). Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomized phase 3 trial. This chapter contains a summary of some key findings from a selection of 18 trials related to oral cavity, nasopharynx, oropharynx, larynx, and hypopharynx cancer. Notably, patients with PR (partial plus major) showed significantly improved 1-year DFS compared to patients with no PR (100% versus 68%, p = 0.01; HR = 0.23). N Engl J Med (2013) 369(2):13444. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. A limited number of drugs have shown activity in advanced disease, and due to the rarity of these tumours, clinical trials in sarcoma include many subtypes and are mainly initiated by academic research groups. doi: 10.1200/JCO.2012.43.8820, 28. Br J Cancer. 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. 2004;350:246170. In the era of precision cancer medicine, innovative trial designs will also require the matching of novel drugs with putative targets. Twenty-nine HNSCC patients with locoregionally recurrent disease who were surgically resectable were treated with neoadjuvant nivolumab and lirilumab, an anti-KIR blocking antibody focused on NK cell checkpoint inhibition. In addition, the dynamic expression change of PD-L1 with tumor heterogeneity also makes it difficult to evaluate the expression of PD-L1 (41). N Engl J Med (1991) 324(24):168590. Three trials are discussed that studied various forms of treatment de-intensification in patients with HPV-positive oropharyngeal carcinoma, including a phase 2 study by ECOG, RTOG 1016, and the De-ESCALaTE trial. Blood. In addition, IC may increase the possibility of severe AEs as compared to CCRT in non-surgical locally, advanced HNSCC treatment. J Immunother Cancer (2021) 9(5):115. Lancet Oncol. As mentioned above, to date neoadjuvant immunotherapy has been shown to be safe and has not resulted in surgical delays. doi: 10.1093/annonc/mdy218, 59. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Nat Commun (2021) 12(1):3349. doi: 10.1038/s41467-021-23355-x, 56. 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. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. Furthermore, tertiary lymphoid structures (TLS) in the tumor bed are suggested tocontribute favorable outcome (55). A trial done by Tata Memorial Centre is included that randomized patients with mostly oral tongue carcinoma to elective neck dissection at the time of primary cancer surgery or watchful waiting with therapeutic neck dissection for nodal relapse. doi: 10.1016/j.cllc.2019.11.003, 62. PubMedGoogle Scholar, Yajnik, S. (2019). Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. 2015;373(1):2334. Rochester, Minn., Jacksonville, Fla. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in JClin Oncol (2018) 36(31):307783. Adaptive designs for dual-agent phase I dose-escalation studies. Clinical outcomes were better than historical with 70% 1-year disease free survival and 85% 1-year overall survival. 2016;35:4907. The immunological responses were analyzed using blood before and after treatment. Google Scholar. The landmark phase III trials in high-grade serous ovarian cancer are testing PARP inhibitors as maintenance therapy after response to platinum-based therapy in relapsed disease. 2016;17(4):42539. Terms and Conditions, These studies with previously untreated tumors may enable establishment of predictive biomarkers to select appropriate patients and also define mechanistic pathways. 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. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Therapeutically, HPV-positive HNSCC demonstrates sensitivity to chemoradiotherapy, and offers a better prognosis (2). This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology. Merlino DJ, Johnson JM, Tuluc M, Gargano S, Stapp R, Harshyne L Jr., et al. He is also Coordinator of the Polish Clinical GIST Registry, and a reviewer for several international scientific journals, as well as a member of the Editorial Board of Annals of Surgical Oncology, BMC Medicine and European Journal of Surgical Oncology. Radiation Oncology Consultants (ROC), Chicago, IL, USA, You can also search for this author in SS: editing the manuscript. radiotherapy for early glottic carcinoma (T1N0M): results of prospective randomized study of radiation fraction size and overall treatment time. With the advent of novel oral agents that are well tolerated and highly efficacious, the therapeutic landscape of CLL underwent radical changes [31]. In another phase II neoadjuvant pembrolizumab clinical trial, we reported no severe grade 3/4 AEs and no surgical delays in a total of 36 treated HNSCC patients (54). All authors contributed to the article and approved the submitted version. 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. His current research is focused on investigating the impact of novel laboratory parameters for assessing prognosis of CLL. However, negative Phase III trials (19, 20) in this setting have reduced enthusiasm for these approaches. HPV infection might also be a clinical biomarker to predict the response to CPIs. CrossRef 11:727433. doi: 10.3389/fonc.2021.727433. To be eligible, patients had to have N2 or N3 adenopathy. Bioinformatics. Overall survival results from a phase III trial of nivolumab combined with ipilimumab in treatment-nave patients with advanced melanoma (CheckMate 067). The goal of cytotoxic chemotherapy in this setting is to directly attack tumor cells to reduce tumor burden. 2009;92:414. HS received funding from the Uehara Foundation (201941070). Neoadjuvant Checkpoint Blockade for Cancer Immunotherapy. Pathologic responses were seen in 12/28 (43%) of patients with 4 having MPR. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. 2016;53:12534. Adaptive randomization of neratinib in early breast cancer. High Tumor Mutation Burden Fails to Predict Immune Checkpoint Blockade Response Across All Cancer Types. HNCA recommends researching head and neck cancer clinical trials either by going to www.ClinicalTrials.gov a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world - or using our Clinical Trial Finder which is designed to be user-friendly for patients. A special article collection in BMC Medicine, Spotlight on landmark oncology trials, features articles from invited experts on recent clinical practice-changing trials. doi: 10.1200/JCO.2019.37.15_suppl.TPS6090, 77. Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, et al. 2018. Being a member of the American Society Clinical Oncology (ASCO), American Society Hematology (ASH), European Society Hematology, he is actively involved in the GIMEMA (Gruppo Italiano Malattie Ematologiche Adulto) lymphoproliferative working group as a member of the working party. Pembrolizumab versus ipilimumab in advanced melanoma. He is a member of several Polish and international scientific societies (Board member and Past-President of Polish Society Surgical Oncology and Ex-member of the Board of Directors of the Connective Tissue Oncology Society). Adjuvant Chemotherapy for Resectable Squamous Cell Carcinomas of the Head and Neck: Report on Intergroup Study 0034. 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. PubMed Central Article Importantly, phase III clinical trials which examined the clinical efficacy of IC treatment prior to surgery also failed to show suppression of loco-regional relapse and distant metastasis or extend OS (2628). Eur J Cancer. N Engl J Med (2018) 378(22):2093104. Landmark Trials in Oncology pp 217239Cite as. The era of precision medicine has led to significant developments in the therapy of advanced soft tissue sarcomas (STS), breast cancer, ovarian cancer and haematological neoplasms, among others. 1. Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. J Clin Oncol (2014) 32(25):273543. Nat Rev Clin Oncol. Head and neck cancer is growing in incidence. 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. Other work showed that PD-L2 expression was significantly correlated with PD-L1 expression in HNSCC clinical samples (42). doi: 10.1056/NEJMoa2002788, 31. doi: 10.1056/NEJMoa1305133, 30. Three HPV-positive tumors and one HPV-negative tumor had partial pathologic responses. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. doi: 10.1002/cncr.33471, 22. doi: 10.1038/s41591-020-0805-8, 36. Key pathological findings after neoadjuvant immunotherapy include 1) keratinous debris, 2) giant cells, histiocytic reaction and 3) tumor necrosis. Postoperative Irradiation With or Without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer. 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. doi: 10.1200/JCO.2021.39.15_suppl.6008, 76. Ann Oncol (2019) 30(1):4456. In this trial, only one patient showed a grade III AE (rash) while no patients had grade IV AE, consistent with the safety and tolerability of neoadjuvant immunotherapy (75). https://doi.org/10.1186/s12916-017-0884-7, DOI: https://doi.org/10.1186/s12916-017-0884-7. Of eighty evaluated patients, 32 patients (40%) showed a PR [26 partial PR ( 20% and <90%) and 6 with major PR (>90%)]. 2016;387(10028):162937. For example, in a phase II trial, platinum combined with immunotherapy (nivolumab) followed by transoral robotic surgery (TORS) or RT/CRT is being examined in oropharyngeal cancer patients (NCT03107182). Successes and failures: what did we learn from recent first-line treatment immunotherapy trials in non-small cell lung cancer? Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J, et al. doi: 10.1007/BF01192200, 63. Moreover, recent trials of immune checkpoint inhibitors in melanoma, non-small cell lung carcinoma, and head and neck cancers have significantly influenced the therapeutic landscape by providing promising evidence for immunotherapy efficacy in the adjuvant setting in high-risk locoregional disease. Additionally, R/M HNSCC patients treated with pembrolizumab plus chemotherapy had significantly prolonged OS compared to the cetuximab with chemotherapy group. Google Scholar. Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR, Tsao A, Stewart DJ, Hicks ME, Erasmus J, Gupta S. The BATTLE trial: personalizing therapy for lung cancer. Nature (2014) 515(7528):57781. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al. Lancet Oncol (2013) 14(3):25764. For all cohorts, there was a 90% clinical to pathologic down staging. However, translational research did not discover any predictive biomarker subgroups [27] for the palbociclib effect. Furthermore, although distinct tumor-suppressor mutations including TP53, CDKN2A, NOTCH have been reported in HNSCC, cancer-promoting driver oncogenic mutations have not been detected (911), which makes it challenging to apply molecular targeted therapies. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A, POPLAR Study Group. J Clin Oncol (2012) 30(15):1796804. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Front Oncol (2020) 10:566315. doi: 10.3389/fonc.2020.566315, 66. doi: 10.1016/S0140-6736(18)31999-8, 14. Second, in contrast to conventional chemotherapy, immunotherapy is much better tolerated by patients. Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. Hellmann MD, Chaft JE, William WN Jr, Rusch V, Pisters KM, Kalhor N, et al. 2015;372(4):32030. The establishment of the best pathological method to evaluate the response of neoadjuvant immunotherapy is still evolving as the ultimate clinical impact of histologic changes is understood. He works very closely with national patient advocacy groups for GIST and sarcoma and is Chairman of the Melanoma Academy in Poland. PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer. Thus, further studies are needed to define the role of TMB as a predictive biomarker. Recent landmark immunotherapy trials - melanoma, Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. Int J Radiat Oncol Biol Phys (1992) 23(3):6712; discussion 6778. Further clinical trials are under way to determine how best to integrate combination immunotherapy and other treatment modalities as well as to establish the correct sequence of therapy with targeted treatment in BRAF-mutated cases. evaluated the role of measuring plasma EBV DNA and is included. McGrail DJ, Pili PG, Rashid NU, Voorwerk L, Slagter M, Kok M, et al. doi: 10.1056/NEJMoa1602252, 13. Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, DAmico TA, DeCamp MM, Dilling TJ, Dobelbower M, Doebele RC, Govindan R, Gubens MA, Hennon M, Horn L, Komaki R, Lackner RP, Lanuti M, Leal TA, Leisch LJ, Lilenbaum R, Lin J, Loo Jr BW, Martins R, Otterson GA, Reckamp K, Riely GJ, Schild SE, Shapiro TA, Stevenson J, Swanson SJ, Tauer K, Yang SC, Gregory K, Hughes M. Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. Intriguingly, TMB was significantly higher among HPV-/EBV- responders and correlated with OS, but not high in HPV+/EBV+ responders who didnt show any correlation between TMB and OS (52). Histological Assessment. Lancet Oncol. doi: 10.1016/S1470-2045(10)70017-6, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. HPV-Associated Head and Neck Cancer: A Virus-Related Cancer Epidemic. Safety and Tumor Responses With Lambrolizumab (Anti-PD-1) in Melanoma. J Clin Oncol (2021) 39(15_suppl):60066. doi: 10.1200/JCO.2017.76.2591, 26. is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer. 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. 2015;373(3):20919. Advances in immunotherapy for melanoma. The head and neck region is anatomically complex and serves essential functions such as eating, speaking, and breathing. doi: 10.1136/jitc-2021-002485, 67. doi: 10.1126/science.1208130, 12. 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). In this trial, pembrolizumab monotherapy significantly improved the OS of PD-L1 positive (CPS 20 or CPS 1) HNSCC. J Clin Oncol (2015) 33(8):83645. Ann Oncol (2018) 29(8):16302. NEngl J Med (2016) 375(19):185667. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. Article In addition to this design, immunotherapy is being integrated in several neoadjuvant combinations with radiation or chemotherapy prior to surgery. doi: 10.1093/annonc/mdt461, 25. Although neither baseline CD8+ T cell infiltration status nor PD-L1 expression level correlated with overall response, there was a trend in which greater CD8+ T cells infiltrated patients tended to show MPR. Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy. Patients also received 6 months of adjuvant nivolumab and lirilumab. 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. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer. A more recent niraparib study had similar results [30], where patients in the niraparib group had a significantly longer PFS than the placebo group in all cohorts tested (21.0 vs. 5.5months in the gBRCA cohort; 12.9 vs. 3.8months in the non-gBRCA cohort for patients who had tumours with homologous recombination deficiency; and 9.3 vs. 3.9months in the overall non-gBRCA cohort; P<0.001). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Laramore GE, Scott CB, al-Sarraf M, Haselow RE, Ervin TJ, Wheeler R, et al. Given that the genomic analyses of HNSCC has not identified widely shared oncogenic driver mutations but shows relatively high TMB (49, 50), the relationship between TMB and response to CPIs is promising. Oncoimmunology (2019) 8(5):e1581530. RU: editing and supervising the manuscript, tables and figure. BMC Med. J Clin Oncol (2021) 39(15_suppl):60088. Ann Oncol (2018) 29(8):185360. Palbociclib in hormone-receptor-positive advanced breast cancer. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. Notably, grade 3/4 serious adverse events or delay of surgery didnt occur, underscoring the safety of neoadjuvant immunotherapy. 2014;15(8):85261. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, et al. 2017. doi:10.1186/s12916-017-0879-4. Lancet. Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. He was/is member of the editorial board of Leukemia and Lymphoma, BMC Medicine, ISRN Hematology and International Journal of Hematologic Oncology. Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, ODwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ, RESONATE-2 Investigators. 2017;35(2):16674. Finally, considering the ease of biopsies in the head and neck region, compared to adjuvant immunotherapy, neoadjuvant immunotherapy has the benefit to enable translational efforts such as TCR analysis, gene-expression profiling, and cytokine evaluation in the primary tumor which is not affected by other treatments including chemotherapeutics or radiation. doi: 10.1158/1078-0432.CCR-19-3977, 71. A. Kaplan R, Maughan T, Crook A, Fisher D, Wilson R, Brown L, Parmar M. Evaluating many treatments and biomarkers in oncology: a new design. In fact, a study evaluating 20 resected non-small cell lung cancer (NSCLC) tumors after neoadjuvant anti-PD-1 treatment showed a discrepancy between radiological and pathological evaluation (58). A Study to Evaluate Fractionated Radiation Therapy Utilizing GRID Therapy for Locally-advanced Bulky Tumors. Oliva M, Spreafico A, Taberna M, Alemany L, Coburn B, Mesia R, et al. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crin L, Blumenschein Jr GR, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. doi: 10.1200/JCO.2017.75.1644, 57. Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. Clin Pharmacol Ther. Harrington JA, Wheeler GM, Sweeting MJ, Mander AP, Jodrell DI. doi: 10.1172/jci.insight.89829, 18. Cooper JS. Both trials demonstrated significant benefit for maintenance PARP inhibitors in all subgroups of platinum-sensitive relapsed high-grade serous ovarian cancer. This was nearly double what we saw with one dose of pembrolizumab. Ann Oncol (2014) 25(2):4626. Notably, any pTR after neoadjuvant pembrolizumab correlated with baseline tumor PD-L1, immune infiltration, and IFN- activity, but not TMB. 2017;15(4):50435. Pembrolizumab Alone or With Chemotherapy Versus Cetuximab With Chemotherapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (KEYNOTE-048): A Randomised, Open-Label, Phase 3 Study. These data highlight the difficulty of interpreting peripheral lymphocyte populations with clinical responses in HNSCC patients treated with neoadjuvant immunotherapy. doi: 10.1200/JCO.2003.06.146, 27. Note, there are institution specific protocols where induction chemotherapy prior to surgery is still used for larger tumors to achieve more rapid control (21). 2009;86(1):97100. To speed up the introduction of targeted therapy for cancer patients, novel phase II trials are being designed, and may likely form the basis for the landmark trials of the future. 2014;371(3):21323. A meta-analysis by Pignon et al. Pignon JP, le Matre A, Maillard E, Bourhis J. Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC): An Update on 93 Randomised Trials and 17,346 Patients. Cite this article. 2006;64(1):7782. 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). The primary cancer (oral cavity) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: Tis, yellow; T1, green; T2, blue; T3, purple; T4A, red; and T4B, black. Nature (2013) 500(7463):41521. The November 3, 2021 "Clinical Trial Endpoint Development" (12pm - 5:00 pm ET) will address Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) Topalian SL, Taube JM, Pardoll DM. These are the first clear data in HNSCC supporting the finding that neoadjuvant anti-PD1 induced PR is a predictor of clinical outcomes. J Clin Oncol. There are three major potential benefits to use CPIs in the neoadjuvant setting. No new safety signals were observed and there were no surgical delays. doi: 10.1016/S0140-6736(19)32591-7, 15. The team lead by Professor Jean-Charles Soria discussed the successes and failures of immunotherapy in the first-line treatment of NSCLC [2]. He is the current Head of the Department of Soft Tissue/Bone Sarcoma and Melanoma, the Plenipotentiary Director of Institute for Clinical Trials at the Maria Sklodowska-Curie Memorial Cancer Center as well as the President of the Scientific Council of Maria Sklodowska-Curie Memorial Cancer Center. Given that CPIs are still expensive drugs and sometimes induce severe immune-related toxicities, it is important to establish the appropriate markers which can predict efficacy of CPIs (39, 40). Bernier J, et al. Article In: Proceedings from the American Association for Cancer Research Annual Meeting, April 25, 2017, Washington DC. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. The studies listed below represent the first major clinical trials to evaluate risk reduction for people at high risk of breast, prostate, lung, colorectal, ovarian, cervical, and lung cancer. The Society for Immunotherapy of Cancer Consensus Statement on Immunotherapy for the Treatment of Squamous Cell Carcinoma of the Head and Neck (HNSCC). 2013;10(5):27788. Management of toxicities in this setting remains a challenge. https://doi.org/10.1007/978-3-030-14405-0_7, Tax calculation will be finalised during checkout. 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: 10.1001/jamaoncol.2020.2955, 69. The RTOG 90-03 trial . All authors read and approved the final manuscript. First, neoadjuvant immunotherapies will enhance systemic T cell responses for tumor-specific antigens before surgery (34). The primary endpoint of this trial was comparison between arms of a change in the CD8+ tumor infiltrating lymphocyte (TIL) density. California Privacy Statement, Part of Springer Nature. Received: 18 June 2021; Accepted: 19 August 2021;Published: 06 September 2021. Mandal R, enbabaolu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, et al.
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