In addition, in the KEYNOTE-040 phase III study, the correlation of clinical outcome and PD-L1 expression on tumor (PD-L1 tumor proportion score 50%) was evident (13). In addition, there was evidence of response in both arms. 2016;375(1):2334. is included that studied the role of chemotherapy in patients undergoing definitive locoregional treatment. The Society for Immunotherapy of Cancer Consensus Statement on Immunotherapy for the Treatment of Squamous Cell Carcinoma of the Head and Neck (HNSCC). 1998;16:13107. He has participated in several investigator-driven trials in melanoma and sarcoma. These results underscore that TPF IC is not recommended for survival benefit. Nat Rev Clin Oncol. HPV-Positive Status Associated With Inflamed Immune Microenvironment and Improved Response to Anti-PD-1 Therapy in Head and Neck Squamous Cell Carcinoma. The Mutational Landscape of Head and Neck Squamous Cell Carcinoma. CAS HPV infection might also be a clinical biomarker to predict the response to CPIs. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, et al. However, some immunological therapeutic effects can induce pseudo-progression or development of new lesions because of infiltration of immune cells into the primary tumor or lymph nodes, which makes it difficult to evaluate the treatment efficacy only with radiographical information (57). doi: 10.1200/JCO.2019.37.15_suppl.TPS6090, 77. Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, et al. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Using a primary radiation based approach, several ongoing clinical trials aim to de-intensify the treatment impact by adding immunotherapy (77). Menzies AM, Amaria RN, Rozeman EA, Huang AC, Tetzlaff MT, van de Wiel BA, et al. Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazz D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Ann Oncol (2018) 29(8):185360. Bertrand Baujat et al. Historically, surgery and radiotherapy with/without conventional chemotherapy including platinum, taxanes or fluorouracil, were applied to treat HNSCC. van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P, EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Google Scholar. Di Veroli et al. Haddad R, ONeill A, Rabinowits G, Tishler R, Khuri F, Adkins D, et al. Merlino DJ, Johnson JM, Tuluc M, Gargano S, Stapp R, Harshyne L Jr., et al. Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, et al. These trials represent the end of the long process of translating scientific innovation and drug discovery, through first-in-man studies, followed by phase II trials and finally by randomised phase III trials as required for licensing of new treatments. In addition to this design, immunotherapy is being integrated in several neoadjuvant combinations with radiation or chemotherapy prior to surgery. In this trial, safety, pTR, and relapse rate with pembrolizumab were evaluated. Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect. doi: 10.1158/1078-0432.CCR-19-3977, 71. PubMed Furthermore, tertiary lymphoid structures (TLS) in the tumor bed are suggested tocontribute favorable outcome (55). Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. Ruffin AT, Cillo AR, Tabib T, Liu A, Onkar S, Kunning SR, et al. Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, et al. on behalf of the MAC-NPC Collaborative Group. In: Landmark Trials in Oncology. Article Nat Rev Clin Oncol. doi: 10.1056/NEJMoa1602252, 13. In conclusion, the RESONATE-2 trial demonstrates that ibrutinib is a new important player in the treatment of elderly unfit patients and in those with high-risk disease. doi: 10.1158/1535-7163.MCT-17-0386, 17. Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, et al. Following this, the phase III KEYNOTE-048 trial established a new paradigm for first-line R/M HNSCC patients (14). Thus, further studies are needed to define the role of TMB as a predictive biomarker. Part of Springer Nature. 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. 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. NIRT did impact healing of wounds that all ultimately resolved. There were no treatment related delays thus achieving the primary safety endpoint. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebb C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. A pooled analysis of data from these two postoperative trials is included, which was designed to analyze the selection criteria, clinical and pathologic risk factors, and outcomes and to establish precisely which patients benefit from the addition of cisplatin to postoperative radiation therapy. Timing of Neoadjuvant Immunotherapy in Relation to Surgery Is Crucial for Outcome. Subsequently the Keynote-048 study, a randomized multi-center phase III study from 37 countries, examined pembrolizumab alone or with chemotherapy (platinum plus fluorouracil) versus cetuximab with chemotherapy (the EXTREME regimen (32)) for first-line treatment of R/M HNSCC (14). strategies for preserving the quality of life during and after treatment. CAS Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy. 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. 2016;387(10028):162937. The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. There are now numerous studies introducing neoadjuvant immunotherapy in diverse cancer types (3436). doi: 10.1002/cncr.33471, 22. These studies with previously untreated tumors may enable establishment of predictive biomarkers to select appropriate patients and also define mechanistic pathways. Ang KK, et al. Notably, the timing of immune checkpoint inhibitors may influence the outcome of cancer treatment (33). There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. Development of Tumor Mutation Burden as an Immunotherapy Biomarker: Utility for the Oncology Clinic. J Clin Oncol (2014) 32(25):273543. Contact: Elizabeth Akoth, 240-858-3154. Ferris RL, Spanos WC, Leidner R, Gonalves A, Martens UM, Kyi C, et al. 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 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). doi: 10.1093/annonc/mdy507, 41. elective versus therapeutic neck dissection in node-negative oral cancer. RU: editing and supervising the manuscript, tables and figure. Abstract CT075. Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. Liu J, Blake SJ, Yong MC, Harjunp H, Ngiow SF, Takeda K, et al. Front Oncol (2020) 10:566315. doi: 10.3389/fonc.2020.566315, 66. 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). Nature (2013) 500(7463):41521. 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. Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Lancet (2014) 384(9938):16472. Nevertheless, the selection of systemic therapy must be strictly individualised and based upon several factors, including the histology and biological behaviour of the disease. 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. 2017. doi:10.1186/s12916-017-0879-4. J Clin Oncol. RU serves on an advisory board for Merck, Inc. 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. Bossi P, Lo Vullo S, Guzzo M, Mariani L, Granata R, Orlandi E, et al. Wang J, Sun H, Zeng Q, Guo XJ, Wang H, Liu HH, et al. Any pTR was seen in 44% and pTR-2 was seen in 22% of patients. Our own group is developing a novel Bayesian, adaptive randomised methodology [47]. 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. These findings highlight the clinical importance to establish standard pathological criteria to accurately evaluate the therapeutic effect of neoadjuvant immunotherapy after definitive surgery. 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/. doi: 10.1093/annonc/mdt461, 25. Papadimitrakopoulou V, Lee JJ, Wistuba II, Tsao AS, Fossella FV, Kalhor N, Gupta S, Byers LA, Izzo JG, Gettinger SN, Goldberg SB, Tang X, Miller VA, Skoulidis F, Gibbons DL, Shen L, Wei C, Diao L, Peng SA, Wang J, Tam AL, Coombes KR, Koo JS, Mauro DJ, Rubin EH, Heymach JV, Hong WK, Herbst RS. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck. Positive results from this study established the application of anti-PD-1 for R/M HNSCC treatment, and proved the existence of actionable, efficient anti-cancer immunity in HNSCC tumors. Another meta-analysis showed that HPV positive HNSCC patients display significant improved outcomes with PD-1/PD-L1 axis blockage treatment compared to HPV negative HNSCC patients (46). B Cell Signatures and Tertiary Lymphoid Structures Contribute to Outcome in Head and Neck Squamous Cell Carcinoma. Note that MPR was observed in 8 (29%) patients in either the primary tumor or lymph node metastasis. In conclusion, neoadjuvant approaches provide a potential exciting new treatment paradigm for HNSCC patients. 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. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. The current mainstay of advanced head and neck squamous cell carcinoma (HNSCC) treatment remains surgery and radiotherapy with/without conventional chemotherapy. The checkmate 141 phase III trial evaluated the effect of anti-PD-1 (nivolumab) for R/M HNSCC patients (12). 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. 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. An important consideration in neoadjuvant immunotherapy approaches is clinical safety as the possibility of lifelong autoimmune complications in the definitive surgical setting needs to be weighed carefully. They used pathological response (PR) criteria which was defined tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris (74). Neoadjuvant Immunotherapy Leads to Pathological Responses in MMR-Proficient and MMR-Deficient Early-Stage Colon Cancers. In addition, IC may increase the possibility of severe AEs as compared to CCRT in non-surgical locally, advanced HNSCC treatment. J Clin Oncol. Int J Radiat Oncol Biol Phys (1996) 36(5):9991004. 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. Burtness B, Harrington KJ, Greil R, Soulires D, Tahara M, de Castro G Jr, et al. Lancet. Differences in T-Cell Infiltrates and Survival Between HPV+ and HPV- Oropharyngeal Squamous Cell Carcinoma. Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. 2017;15:57. doi: 10.1126/science.aar3593, 52. Manage cookies/Do not sell my data we use in the preference centre. This trial included both definitive and salvage surgery patients. Head Neck. Saad ED, Paoletti X, Burzykowski T, Buyse M. Precision medicine needs randomized clinical trials. BMC Med 15, 111 (2017). 2014;15(8):85261. (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). 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. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomized trials and 17,346 patients. 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). Frameshift Events Predict Anti-PD-1/L1 Response in Head and Neck Cancer. Multi-disciplinary treatments, integrating surgery, chemotherapy, and radiation, aim to maximize treatment effects but have significant functional impact. The expression level of PD-L1 in the tumor does not necessarily correlate withthe response to CPIs. 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. doi: 10.1016/S0140-6736(18)31999-8, 14. Hitt R, Grau JJ, Lpez-Pousa A, Berrocal A, Garca-Girn C, Irigoyen A, et al. Xu Y, Zhu G, Maroun CA, Wu IXY, Huang D, Seiwert TY, et al. Defining Risk Levels in Locally Advanced Head and Neck Cancers: AComparative Analysis of Concurrent Postoperative Radiation Plus Chemotherapy Trials of the EORTC (#22931) and RTOG (# 9501). 11:727433. doi: 10.3389/fonc.2021.727433. Mandal R, enbabaolu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, et al. The landmark Docetaxel-Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DECIDE) trial randomized 285 patients between 2004 and 2009 to concurrent chemoradiation plus or minus induction chemotherapy. 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. Pathologic Features of Response to Neoadjuvant Anti-PD-1 in Resected Non-Small-Cell Lung Carcinoma: A Proposal for Quantitative Immune-Related Pathologic Response Criteria (irPRC). J Clin Oncol (2019) 37(15_suppl):25755. 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). doi: 10.1056/NEJMoa031317, 24. Science (2011) 333(6046):115760. N Engl J Med (1991) 324(24):168590. Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. 2016;387:154050. Zuur CL, Elbers JBW, Vos JL, Avd L, Qiao X, Karakullukcu B, et al. A potential shortcoming with the upfront use of ibrutinib includes cost and indefinite treatment course [37]. 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. 1991;324:168590. In addition to the published studies above, several ongoing neoadjuvant immunotherapy trials with subsequent surgery for locally advanced HNSCC have reported results at major oncology meetings (Table2). 2015;373(3):20919. HE, SM and PR contributed equally to drafting, editing and revision of the manuscript. 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. Lancet. 2016;34(Suppl; abstr 9504). Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. PubMed CAS Al-Saraff M, et al. Neoadjuvant Immunoradiotherapy Results in High Rate of Complete Pathological Response and Clinical to Pathological Downstaging in Locally Advanced Head and Neck Squamous Cell Carcinoma. that compared radiation therapy plus or minus cetuximab, and RTOG 0522 are included as landmark trials in the development of an organ preservation approach for the management of locoregionally advanced disease. The team lead by Professor Jean-Charles Soria discussed the successes and failures of immunotherapy in the first-line treatment of NSCLC [2]. Ann Oncol (2014) 25(1):21625. 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. Springer, Cham. All authors read and approved the final manuscript. California Privacy Statement, Spotlight on landmark oncology trials: the latest evidence and novel Science (2018) 362(6411):110. 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. [39] published an interesting software to provide information in terms of synergy and/or antagonism between two compounds. 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). Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebb C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A. Article These encouraging findings have led to numerous ongoing studies testing combinations to improve CPI response rates and also testing these agents in other settings. Delay to Surgery After Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Affects Oncologic Outcomes. 2009;92:414. Bonner J, et al. Impact of Neoadjuvant Durvalumab With or Without Tremelimumab on CD8(+) Tumor Lymphocyte Density, Safety, and Efficacy in Patients With Oropharynx Cancer: CIAO Trial Results. doi: 10.1093/annonc/mdt555, 29. Understanding Patterns of Pathologic Response Following Neoadjuvant Immunotherapy for Solid Tumors. Indeed, BATTLE, a landmark phase II trial using an adaptive randomised design, tested four novel drugs and biomarker pairings in NSCLC [41]. Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. 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. Landmark Trials in Selected Head and Neck Cancers - ResearchGate doi: 10.1200/JCO.2021.39.15_suppl.6008, 76. Palbociclib in hormone-receptor-positive advanced breast cancer. A study by Yamazaki et al. The three-planar views are crucial to understanding the malignant gradient. There was an 86% MPR rate and a 67% pCR rate. In the neoadjuvant immunotherapy context, immune-modified RECIST (imRECIST) criteria have been proposed (56). 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. doi: 10.1158/2159-8290.CD-16-0577, 38. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. doi: 10.1200/JCO.2017.76.2591, 26. Lancet Oncol. A. 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. New treatment destroys head and neck cancer tumours in trial Clinical Trials - Head and Neck Cancer Alliance 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%. 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). Hanna GJ, Lizotte P, Cavanaugh M, Kuo FC, Shivdasani P, Frieden A, et al. Harrington JA, Wheeler GM, Sweeting MJ, Mander AP, Jodrell DI. Notably, grade 3/4 serious adverse events or delay of surgery didnt occur, underscoring the safety of neoadjuvant immunotherapy. 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. 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). N Engl J Med. 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]. doi: 10.1056/NEJMoa1801946, 48. 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. 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. More effective and cost-efficient phase II trial designs would rapidly lead to landmark trials and practice-changing results. 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. SS: editing the manuscript. To be eligible, patients had to have N2 or N3 adenopathy. This enhanced function acts to destroy micro-metastasis in clinically advanced tumors, decreasing loco-regional or distant metastasis after primary therapies. doi: 10.1200/JCO.2011.38.8595, 60. Lancet Oncol. An important consideration in neoadjuvant immunotherapy approaches is appropriate patient selection. 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). Hanna GJ, ONeill AM, Jo VY, Wong K, Lizotte PH, Annino DJ, et al. 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). Google Scholar. 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). PubMedGoogle Scholar, Yajnik, S. (2019). 2014;371(3):21323. Szturz P, Vermorken JB. 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). Front. BMC Cancer (2020) 20(1):229. doi: 10.1186/s12885-020-06726-3, 70. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. 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 . N Engl J Med (2004) 350(19):194552. Pignon J-P, et al. In HNSCC, anti-PD-1 agents (nivolumab, pembrolizumab) were first examined and approved in R/M setting. These designs would allow recruitment of biomarker-negative patients, often not included in other trials, and have the potential for perpetual designs, in which successful matching of novel drugs and biomarkers would result in graduation of the pair to a phase III trial, along with the rapid rejection of novel drugs that did not work.
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