N Engl J Med (2003) 349(22):20918. 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. J Clin Oncol. Although only 15-20% of patients benefit, immunotherapies have been approved and widely used for recurrent and metastatic HNSCC. Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J, et al. 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. Tumour Regression in Non-Small-Cell Lung Cancer Following Neoadjuvant Therapy. doi: 10.1080/2162402X.2019.1581530, 34. Wise-Draper TM, Takiar V, Mierzwa ML, Casper K, Palackdharry S, Worden FP, et al. 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). 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. 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. IC continues to be used at some centers with defined indications including advanced or borderline resectable tumors. Ann Oncol (2018) 29(8):185360. We and others have focused on HPV-negative, locally advanced disease patients with high-risk pathologic features (positive surgical margins or extra-nodal extension). He was/is member of the editorial board of Leukemia and Lymphoma, BMC Medicine, ISRN Hematology and International Journal of Hematologic Oncology. N Engl J Med. CrossRef These data suggest that virus infection status impacts TMB as a biomarker. J Radiat Oncol Biol Phys. doi: 10.1001/jamaoncol.2020.2955, 69. J Clin Oncol. The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. 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. In Checkmate-141 phase III trial, there wasno correlation of survival extension and PD-L1 expression on tumors (PD-L1+ >1%, 5% and 10%) (12). Merlino DJ, Johnson JM, Tuluc M, Gargano S, Stapp R, Harshyne L Jr., et al. - 50.249.249.18. Ferrarotto R, Bell D, Rubin ML, Hutcheson KA, Johnson JM, Goepfert RP, et al. N Engl J Med. Major pathological responses were seen in 1 HPV-positive tumor with none in the HPV-negative tumors. 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. Lancet Oncol. Frameshift Events Predict Anti-PD-1/L1 Response in Head and Neck Cancer. 2015;373(1):2334. Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, et al. Lin J-C, et al. doi: 10.1200/JCO.2003.06.146, 27. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. In addition, CD8+ T cells with lymphocyte-activation gene 3 (LAG-3) or T cell immunoglobulin domain and mucin domain-3 (TIM-3) co-expression with PD-1 was higher among non-responders (52). Bayesian adaptive designs for biomarker trials with biomarker discovery. These trials relate to the multidisciplinary management of head and neck cancer from the perspective of a radiation oncologist. N Engl J Med (2013) 369(2):13444. Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, et al. Uppaluri R, Chernock R, Mansour M, Jackson R, Rich J, Pipkorn P, et al. N Engl J Med (1991) 324(24):168590. 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 . RU serves on an advisory board for Merck, Inc. 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). In addition, IC may increase the possibility of severe AEs as compared to CCRT in non-surgical locally, advanced HNSCC treatment. Comprehensive Genomic Characterization of Head and Neck Squamous Cell Carcinomas. IC resulted in larynx preservation but did not contribute to improved survival. An important consideration in neoadjuvant immunotherapy approaches is appropriate patient selection. doi: 10.1200/JCO.2014.58.6412, 3. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, et al. 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. Bernier J, et al. In this trial, safety, pTR, and relapse rate with pembrolizumab were evaluated. 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). He has participated in several investigator-driven trials in melanoma and sarcoma. This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology. Clin Cancer Res (2020) 26(3):67989. In addition, as other checkpoints are testing, further improvements in pathologic responses and clinical outcomes are expected. 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). High Tumor Mutation Burden Fails to Predict Immune Checkpoint Blockade Response Across All Cancer Types. a landmark trial conducted by Bonner and colleagues evaluating the role of cetuximab plus radiation vs radiation alone, and several induction trials evaluating TPF vs cisplatin . 2005;27:84350. New treatment destroys head and neck cancer tumours in trial evaluated the role of measuring plasma EBV DNA and is included. Science (2020) 367(6477):19. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. N Engl J Med. Despite optimal local treatment, approximately 50% of adult patients with localised STS develop distant metastases and die of metastatic disease. 2014;371(3):21323. The landmark VA Larynx study compared IC (cisplatin and fluorouracil) followed by RT versus total laryngectomy followed by RT in advanced laryngeal cancer (22). This overview examines the treatment history of neoadjuvant approaches for HNSCC, and especially focuses on the recent topics of neoadjuvant immunotherapy for HNSCC. 2015;372(4):32030. Platinum-Based Chemotherapy Plus Cetuximab in Head and Neck Cancer. 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. PubMed 2012;31:84552. Patients with high-TMB have more effective clinical responses with improved survival in lung, bladder, and head and neck cancer patients (47, 48). As further investigation of these intriguing results is needed, the SITC HNSCC immunotherapy guidelines does not recommend using HPV status for anti-PD1 treatments in R/M HNSCC (31). These studies with previously untreated tumors may enable establishment of predictive biomarkers to select appropriate patients and also define mechanistic pathways. 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. doi: 10.1038/nature13988, 16. Pathologic complete response means the ablation of all cancer cells in resected tumor after the treatment. JCI Insight (2018) 3(4):113. For larynx cancer, this approach was initially focused on reducing metastases, and preserving laryngeal function including speech and swallowing. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al. Contact: Elizabeth Akoth, 240-858-3154. is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. 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). Lancet (2019) 394(10212):191528. Remon J, Besse B, Soria JC. doi: 10.4155/fso.15.88, 44. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomized controlled trial. doi: 10.1056/NEJMoa1801946, 48. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. *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 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. Price KAR, Nichols AC, Shen CJ, Rammal A, Lang P, Palma DA, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. 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. Front. RU is funded by NIH/NIDCR R01DE024403, R01DE027736, and NIH/NCI/NIDCR U01DE029188. The RTOG 90-03 trial compared four radiation therapy fractionation schemes for locoregionally advanced patients undergoing radiation therapy alone and is discussed. Am Soc Clin Oncol Educ Book (2020) 40:113. Di Veroli GY, Fornari C, Wang D, Mollard S, Bramhall JL, Richards FM, Jodrell DI. HPV-related oropharyngeal HNSCC shows better survival related to HPV-negative oropharyngeal HNSCCs. Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. Table1 Completed neoadjuvant immunotherapy clinical trials. Radiother Oncol (2009) 92(1):414. 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. Lancet Oncol. JAMA Oncol (2016) 2(1):4654. Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients With Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck. Lancet (2019) 393(10167):15667. Multi-disciplinary treatments, integrating surgery, chemotherapy, and radiation, aim to maximize treatment effects but have significant functional impact. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. We reported a phase II trial, in which neoadjuvant/adjuvant pembrolizumab was tested in locally advanced, resectable HPV-negative HNSCC patients (NCT02296684) (54). Sci Rep (2019) 9(1):13404. doi: 10.1038/s41598-019-49771-0, 46. J Natl Compr Canc Netw. Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, et al. Bonner J, et al. 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 . 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. doi: 10.1016/j.radonc.2009.04.014, 9. This trial aims to enroll 600 patients. doi: 10.1126/science.aax0182, 35. Abstract CT075. A natural extension of this work has led several groups to test whether neoadjuvant chemotherapy prior to surgery would improve clinical outcomes. 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. 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]. Head And Neck Cancer - SlideShare J Immunother Cancer (2021) 9(6):111. Spotlight on landmark oncology trials: the latest evidence and novel 1. 2009;86(1):97100. Lancet Oncol. Pathological Response and Survival With Neoadjuvant Therapy in Melanoma: A Pooled Analysis From the International Neoadjuvant Melanoma Consortium (INMC). We and others have focused on the definitive surgical setting with integration of neoadjuvant immunotherapy and in this review focus on historical and current approaches. Pignon J-P, et al. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. He is also an active member of the EORTC Melanoma Group and the Global Melanoma Task Force. doi: 10.1038/nature14129, 11. N Engl J Med (2020) 383(13):121830. Hitt R, Grau JJ, Lpez-Pousa A, Berrocal A, Garca-Girn C, Irigoyen A, et al. doi: 10.1158/1078-0432.CCR-20-1695, 55. He works very closely with national patient advocacy groups for GIST and sarcoma and is Chairman of the Melanoma Academy in Poland. 2016;53:12534. Marur S, DSouza G, Westra WH, Forastiere AA. The immunological responses were analyzed using blood before and after treatment. 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. Nivolumab (3 mg/kg) was administered on weeks 1 and 3, while ipilimumab (1 mg/kg) was given on week 1 only. A clinical trial studying the side effects of chemotherapy for patients with locally recurrent head and neck squamous cell carcinoma. Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS. BMC Med. 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). doi: 10.1002/hed.20279, 7. Molica S. Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future. Future Sci OA (2016) 2(1):Fso88. Szturz P, Vermorken JB. Curran MA, Montalvo W, Yagita H, Allison JP. N Engl J Med (2018) 378(22):2093104. NIRT did impact healing of wounds that all ultimately resolved. All authors read and approved the final manuscript. doi: 10.1016/0360-3016(92)90642-U, 4. 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. doi: 10.1172/jci.insight.98811, 53. 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. Impact of Neoadjuvant Durvalumab With or Without Tremelimumab on CD8(+) Tumor Lymphocyte Density, Safety, and Efficacy in Patients With Oropharynx Cancer: CIAO Trial Results. J Clin Oncol (2015) 33(8):83645. 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). First published on Mon 11 Oct 2021 07.19 EDT. 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. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynxECOG-ACRIN Cancer Research Group. J Natl Compr Canc Netw. N Engl J Med. 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. 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. Safety and Tumor Responses With Lambrolizumab (Anti-PD-1) in Melanoma. Notably, any pTR after neoadjuvant pembrolizumab correlated with baseline tumor PD-L1, immune infiltration, and IFN- activity, but not TMB. Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Mller KM. J Clin Oncol (2019) 37(15_suppl):25755. Liu J, Blake SJ, Yong MC, Harjunp H, Ngiow SF, Takeda K, et al. Although these Level 1 data established a new postoperative standard of care to treat high-risk HNSCC patients, the five-year survival rate in for these patients remains suboptimal. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. No use, distribution or reproduction is permitted which does not comply with these terms. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in 2016;34(30):363847. National Cancer Center Hospital East, Japan, University General Hospital Attikon, Greece. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 2012;379:187986. Recent landmark trials in HER2-positive breast cancer include those using dual HER2-targeted therapy pertuzumab and trastuzumab with docetaxel. Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. BMC Medicine chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. Landmark Trials. 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). 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. N Engl J Med. BMC Med. These data suggest the reactivity of neoadjuvant immunotherapy is related to immunogenic phenotype before treatment and highlights the future possibility to select patients for neoadjuvant immunotherapy before surgery. 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). The probability of response to CPIs has at least in part been linked to TMB across cancer types, including HNSCC (16). 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. J Clin Oncol (2013) 31(6):74451. 2017. doi:10.1186/s12916-017-0872-y. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. 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). Earl, H., Molica, S. & Rutkowski, P. Spotlight on landmark oncology trials: the latest evidence and novel trial designs. 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. Springer Nature. 2006;64(1):4756. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. safer and more-effective approaches to head and neck radiation therapy. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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. 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. Notably, other work has contradicted the above studies on TMB and concluded that that high TMB failed to predict the effect of ICI (53). This trial included both definitive and salvage surgery patients. In neoadjuvant breast cancer, the I-SPY 1 and 2 trials have successfully matched treatment and biomarkers, using adaptive randomised designs [43, 44]. In HNSCC, anti-PD-1 agents (nivolumab, pembrolizumab) were first examined and approved in R/M setting. Immunological Effects of Nivolumab Immunotherapy in Patients With Oral Cavity Squamous Cell Carcinoma. Note, there are institution specific protocols where induction chemotherapy prior to surgery is still used for larger tumors to achieve more rapid control (21). 2010;11:218. These included oral mucositis and one patient with autoimmune diabetes (68) and there were no surgical delays. These data indicate that PD-L1 expression on tumor cells is not a perfect biomarker to predict the clinical outcome. Int J Radiat Oncol Biol Phys. 2014;14:31723. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. J Clin Oncol (2003) 21(2):32733. Haddad R, et al. Google Scholar. Sholl LM. doi: 10.1200/JCO.2017.76.2591, 26. As trials mature, patient selection for neoadjuvant immunotherapy will need to be defined further. SS: editing the manuscript. These results clearly demonstrate the superiority of dual HER2-directed therapy. This is a preview of subscription content, access via your institution. 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. In this editorial, we discuss the special article collection entitled Spotlight on landmark oncology trials recently published in BMC Medicine, which focuses on the core clinical trials of selected solid tumours (lung cancer [2], melanoma [3, 4], STS [5], head and neck cancer [6]). 2015;373(25):242537. Oliva M, Spreafico A, Taberna M, Alemany L, Coburn B, Mesia R, et al. Novel Strategies to Effectively De-Escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions. Table2 Ongoing neoadjuvant immunotherapy clinical trials. 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. 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. Moreover, three anti-PD-1/anti-PD-L1 agents, pembrolizumab, nivolumab and atezolizumab, have been approved for second-line therapy of NSCLC [16,17,18]; however, contrary to melanoma, patient selection to therapy should be based on PD-L1 expression level of tumour cells. 2015;373(3):20919. 2016;35:4907. HS received funding from the Uehara Foundation (201941070). Clinical Trials - Head and Neck Cancer Alliance 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. 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. Notably, the timing of immune checkpoint inhibitors may influence the outcome of cancer treatment (33). Clin Cancer Res (2020) 26(19):514052. She has been an expert advisor for NHS NICE Health Technology Assessments. N Engl J Med. doi: 10.1002/cncr.33471, 22. 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. Management of toxicities in this setting remains a challenge. Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus-Related Oropharyngeal Carcinomas. Blood. 2017;15:57. They used pathological response (PR) criteria which was defined tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris (74). These patients have the worst prognosis despite multimodality approaches and may benefit from neoadjuvant/adjuvant immunotherapy. CAS doi: 10.1056/NEJMoa2002788, 31. Induction Chemotherapy Plus Radiation Compared With Surgery Plus Radiation in Patients With Advanced Laryngeal Cancer. There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. doi: 10.1200/JCO.2013.54.6309, 21. Lancet Oncol. J Immunother Cancer (2021) 9(5):115. 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. Clinical outcomes were better than historical with 70% 1-year disease free survival and 85% 1-year overall survival. However, while pCR and MPR are considered the gold standard, they do not take into account lesser degrees of immunological reaction in the tumor that may still impact clinical outcomes. 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. Landmark Trials in Selected Head and Neck Cancers Pathologic responses were evaluated in 34 patients (17 HPV+ and 17 HPV-negative). Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new. Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. In: Landmark Trials in Oncology.
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