landmark trials in head and neck cancer ppt

Based on KEYNOTE-048, the FDA approved use of pembrolizumab monotherapy in the first-line for R/M HNSCC with CPS 1 and pembrolizumab plus platinum-based chemotherapy for those with CPS<1 R/M HNSCC (31). 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. In the neoadjuvant immunotherapy context, immune-modified RECIST (imRECIST) criteria have been proposed (56). Key pathological findings after neoadjuvant immunotherapy include 1) keratinous debris, 2) giant cells, histiocytic reaction and 3) tumor necrosis. PubMed Central chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. Enhanced Pathologic Tumor Response With Two Cycles of Neoadjuvant Pembrolizumab in Surgically Resectable, Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC). J Clin Oncol (2017) 35(14):15429. Filter this list of studies by location, status and more. doi: 10.1200/JCO.2016.70.1524, 45. Chen Q, Jain N, Ayer T, Wierda WG, Flowers CR, OBrien SM, Keating MJ, Kantarjian HM, Chhatwal J. Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, et al. 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]. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefbvre JL, Greiner RH, et al. The goals of induction chemotherapy are to achieve rapid tumor responses in particular with large volume disease and to chemo-select patients prior for definitive (chemo)radiotherapy or surgery. N Engl J Med. In this article series, worldwide renowned experts in their fields provided an extensive overview on the state of the art in immunotherapy and discussed the possible future paths in these, still difficult, types of malignancies. This is a preview of subscription content, access via your institution. The Department of Veterans Affairs Laryngeal Cancer Study Group. J Clin Oncol (2018) 36(9):8508. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. There was an 86% MPR rate and a 67% pCR rate. The strength of the study also relies on the good tolerance profile of ibrutinib, which allows it to be administered continuously and provide indefinite disease suppression even in elderly or unfit CLL patients. J Clin Oncol (2021) 39(15_suppl):60066. Clin Cancer Res (2020) 26(13):32119. More effective and cost-efficient phase II trial designs would rapidly lead to landmark trials and practice-changing results. IC resulted in larynx preservation but did not contribute to improved survival. doi: 10.1200/JCO.2021.39.15_suppl.6008, 76. J Clin Oncol (2013) 31(6):74451. doi: 10.1016/S0140-6736(19)32591-7, 15. Neoadjuvant Checkpoint Blockade for Cancer Immunotherapy. Int J Radiat Oncol Biol Phys. Despite these efforts to improve clinical prognosis, the five-year survival rate of locally advanced stage III/IV HNSCC patients is still sub-optimal [53% in postoperative CCRT treated patients (7)], and half of advanced patients show recurrence within three years (8). HE has received research funding from Cancer Research UK and the NIHR HTA, and is funded by the NIHR Cambridge Biomedical Research Centre. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Considering the TME will be dramatically changed after therapeutic treatment, neoadjuvant immunotherapy for HNSCC can provide an opportunity to establish immune markers to predict efficacy of subsequent immunotherapy. Comprehensive Genomic Characterization of Head and Neck Squamous Cell Carcinomas. 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%. Article doi: 10.1200/JCO.2011.38.8595, 60. Kaplan R, Maughan T, Crook A, Fisher D, Wilson R, Brown L, Parmar M. Evaluating many treatments and biomarkers in oncology: a new design. Neoadjuvant chemotherapy has a long history in HNSCC where induction chemotherapy (IC) prior to conventional platinum-based chemotherapy has been tested in numerous studies HNSCC (18). The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral Squamous Cell Carcinoma. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A. KEYNOTE-006 investigators. Lancet Oncol. Immunological Effects of Nivolumab Immunotherapy in Patients With Oral Cavity Squamous Cell Carcinoma. 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). A new cancer treatment can wipe out tumours in terminally ill head and neck cancer patients, scientists have discovered. doi: 10.1016/S1470-2045(13)70011-1, 20. Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, et al. doi: 10.1056/NEJMoa2002788, 31. 2010;11:218. 2014;89(1):1320. Neoadjuvant Immunotherapy Leads to Pathological Responses in MMR-Proficient and MMR-Deficient Early-Stage Colon Cancers. doi: 10.1158/2159-8290.CD-16-0577, 38. doi: 10.1056/NEJMoa1716078, 37. doi: 10.1200/JCO.2012.43.8820, 28. Wise-Draper TM, Takiar V, Mierzwa ML, Casper K, Palackdharry S, Worden FP, et al. 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. For example, a phase II/III trial in patients with early-stage HPV-positive HNSCC is testing whether RT plus chemotherapy (cisplatin) or immunotherapy (nivolumab or durvalumab) can be used for de-intensification (NCT03952585, NCT03410615). These data highlight the difficulty of interpreting peripheral lymphocyte populations with clinical responses in HNSCC patients treated with neoadjuvant immunotherapy. These findings highlight the clinical importance to establish standard pathological criteria to accurately evaluate the therapeutic effect of neoadjuvant immunotherapy after definitive surgery. RU is funded by NIH/NIDCR R01DE024403, R01DE027736, and NIH/NCI/NIDCR U01DE029188. Google Scholar. Lancet. Ther Adv Med Oncol (2021) 13:1758835920984061. doi: 10.1177/1758835920984061, 40. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck. The EORTC 22931 and RTOG 9501 trials were published in 2004 and demonstrated that the addition of concurrent cisplatin chemotherapy to radiation therapy in the postoperative setting improved outcomes for selected (based on pathologic features) patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. The era of precision oncology is marked with prominent successes in the therapy of advanced soft tissue sarcomas, breast cancer, ovarian cancer and haematological neoplasms, among others. Long term results of TAX324, a randomized phase III trial of sequential therapy with TPF versus PF in locally advanced squamous cell cancer of the head and neck. PR reports personal fees (honoraria for lectures and Advisory Board Member) from Novartis, BMS, Roche, MSD, GSK, Pfizer, and Amgen outside the submitted work. Clin Lung Cancer (2020) 21(4):3418. Nevertheless, the selection of systemic therapy must be strictly individualised and based upon several factors, including the histology and biological behaviour of the disease. First, neoadjuvant immunotherapies will enhance systemic T cell responses for tumor-specific antigens before surgery (34). is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer. Front Immunol (2021) 12:645170. doi: 10.3389/fimmu.2021.645170, 47. 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 (2013) 369(2):13444. 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). 2005;27:84350. CAS J Clin Oncol. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. Recent landmark immunotherapy trials - melanoma, doi:10.1080/17474086.2017.1313108. cancer [2], melanoma [3, 4], STS [5], head and neck cancer [6]). Improved Efficacy of Neoadjuvant Compared to Adjuvant Immunotherapy to Eradicate Metastatic Disease. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Xu Y, Zhu G, Maroun CA, Wu IXY, Huang D, Seiwert TY, et al. Despite this multi-modality treatment, advanced human papillomavirus (HPV)-negative HNSCC shows poor prognosis. Nature (2015) 517(7536):57682. Lancet Oncol. However, PD-L1 negative tumors sometimes respond to CPI treatment, suggestingthe existence of other mechanisms. Checkpoint inhibitors (CPI) targeting the programmed death 1 (PD-1) pathway have been approved for recurrent and metastatic (R/M) HNSCC patients in the first- and second-line settings (1214) and have dramatically changed the treatment algorithm of HNSCC. Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy. The radiographic volumetric response (RVR) and PTE were evaluated, and the results of RVR and PTE was significantly correlated in primary tumor and lymph nodes. 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. With the advent of novel oral agents that are well tolerated and highly efficacious, the therapeutic landscape of CLL underwent radical changes [31]. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. (NCT03021993), in which a total of 10 locally advanced OSCC patients were treated with neoadjuvant nivolumab (3 mg/kg on days 1, 14 and 28) (69). Association of Pathological Response to Neoadjuvant Pembrolizumab With Tumor PD-L1 Expression and High Disease-Free Survival (DFS) in Patients With Resectable, Local-Regionally Advanced, Head and Neck Squamous Cell Carcinoma (HNSCC). Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in 2014;14:31723. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus-Related Oropharyngeal Carcinomas. Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, et al. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mdry R, Christensen RD, Berek JS, Drum A, Tinker AV, du Bois A, Gonzlez-Martn A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA, ENGOT-OV16/NOVA Investigators. Pathologic treatment effect (PTE) is another similar scale, which is evaluated by the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area (65). Nature (2013) 502(7471):3339. In addition to this design, immunotherapy is being integrated in several neoadjuvant combinations with radiation or chemotherapy prior to surgery. Delay to Surgery After Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Affects Oncologic Outcomes. 2012;366(15):138292. Mutational Landscape and Significance Across 12 Major Cancer Types. J Clin Oncol. TMB is a potential predictive biomarker that also needs further exploration. However, a potential setback is represented by the control arm since chlorambucil is no longer regarded an adequate therapy in CLL [26]. Ann Oncol (2019) 30(1):4456. These patients have the worst prognosis despite multimodality approaches and may benefit from neoadjuvant/adjuvant immunotherapy. HPV-related oropharyngeal HNSCC shows better survival related to HPV-negative oropharyngeal HNSCCs. Although a total of 21 patients experienced AEs, including grade 3/4 AEs in 2 (N) and 5 (N+I) patients, there were no surgical delays. 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]. Several landmark trials established the clinical benefit of using cisplatin-based chemoradiotherapy after surgery for locally advanced, high-risk HNSCC patients (3, 4). Nat Med (2020) 26(4):56676. Timing of Neoadjuvant Immunotherapy in Relation to Surgery Is Crucial for Outcome. In this review, we present a brief overview of the history of neoadjuvant (induction) chemotherapy in the definitive surgical management of HNSCC. 1998;16:13107. We classified pTR into pTR-0 (10%), pTR-1 (10-49%), and pTR-2 (50%) (54). The importance of BTK inhibitors in the first-line setting has been recently investigated in the RESONATE-2 study [33], a head-to-head clinical trial in which outcomes were shown to be superior for patients who received ibrutinib in comparison to patients treated with chlorambucil single agent. doi: 10.1200/JCO.2017.75.1644, 57. However, as immunotherapy has associated toxicities (see section on this below) and is expensive, careful patient selection to determine who may benefit from these approaches is critical. 2006;64(1):4756. 2012;31:84552. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomized trials and 17,346 patients. Atezolizumab versus docetaxel for patients with previously treated nonsmall-cell lung cancer (POPLAR): a multicentre, open label, phase 2 randomised controlled trial. The RTOG 90-03 trial . Notably, the timing of immune checkpoint inhibitors may influence the outcome of cancer treatment (33). To be eligible, patients had to have N2 or N3 adenopathy. N Engl J Med. Palbociclib in hormone-receptor-positive advanced breast cancer. Di Veroli et al. N Engl J Med (1991) 324(24):168590. 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. KEYNOTE-689: Phase 3 Study of Adjuvant and Neoadjuvant Pembrolizumab Combined With Standard of Care (SOC) in Patients With Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma. doi: 10.1007/BF01192200, 63. Hanna GJ, Lizotte P, Cavanaugh M, Kuo FC, Shivdasani P, Frieden A, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. Figure1 Representative figure of pathological tumor response (pTR). https://doi.org/10.1007/978-3-030-14405-0_7, DOI: https://doi.org/10.1007/978-3-030-14405-0_7. HPV infection results in production of virus-related proteins, which may induce de novo T cell response and more CD8+ T cell infiltration in tumor (43). 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. Secondary endpoints are OS, complete pathological response, and assessment of safety and tolerability. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. N Engl J Med. N Engl J Med. Differences in T-Cell Infiltrates and Survival Between HPV+ and HPV- Oropharyngeal Squamous Cell Carcinoma. PubMed Ann Oncol (2014) 25(2):4626. 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). doi: 10.1056/NEJMoa031317, 24. doi: 10.1136/jitc-2021-002485, 67. 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. She has also received unrestricted educational grants to support investigator initiated clinical trials from Lilly, Roche and Sanofi Aventis, and has received free gemcitabine from Lilly and free bevacizumab from Roche for clinical trials. 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. N Engl J Med (2004) 350(19):193744. doi: 10.1016/S0360-3016(96)00430-0, 5. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. In a landmark trial, a cocktail of immunotherapy medications harnessed patients' immune systems to kill their own cancer cells and prompted "a positive trend in survival . 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. In addition, adaptive designs for phase I combinations are being developed [40]. SM currently serves as referee for several haematology and oncology journals such as Journal Clinical Oncology, Blood, Haematologica, Leukemia Research, Leukemia, Leukemia & Lymphoma, European Journal Haematology, Cancer, British Journal of Haematology, and Lancet Haematology. 2016;388(10043):48897. evaluated the role of measuring plasma EBV DNA and is included. Oncoimmunology (2019) 8(5):e1581530. Patients with high-TMB have more effective clinical responses with improved survival in lung, bladder, and head and neck cancer patients (47, 48). N Engl J Med (2018) 378(22):2093104. These trials will test the important topic of whether there is synergy in combination approaches with RT, immunotherapy and/or chemotherapy. The BATTLE-2 Study: a biomarker-integrated targeted therapy study in previously treated patients with advanced nonsmall-cell lung cancer. 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). Int J Radiat Oncol Biol Phys (1992) 23(4):70513. 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. 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. Analysis of the data gathered from these large trials continues to contribute valuable understanding about related issues, including . Head and neck cancer was the seventh most common cancer worldwide in 2018 (890,000 new cases and 450,000 deaths), 1 accounting for 3% of all cancers (51,540 new cases) and just over . 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. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomized controlled trial. blog writing examples for exams, i bought my husband a dress, the country club pepper pike membership cost,
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