Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Understanding Patterns of Pathologic Response Following Neoadjuvant Immunotherapy for Solid Tumors. doi: 10.1038/s41591-020-01188-3, 65. The goal of cytotoxic chemotherapy in this setting is to directly attack tumor cells to reduce tumor burden. 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. Remon J, Besse B, Soria JC. 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. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Induction Chemotherapy Plus Radiation Compared With Surgery Plus Radiation in Patients With Advanced Laryngeal Cancer. These trials will test the important topic of whether there is synergy in combination approaches with RT, immunotherapy and/or chemotherapy. doi: 10.1038/nature14129, 11. doi: 10.1200/JCO.2014.58.6412, 3. Lancet Oncol. There are now numerous studies introducing neoadjuvant immunotherapy in diverse cancer types (3436). The head and neck region is anatomically complex and serves essential functions such as eating, speaking, and breathing. In this review, we present a brief overview of the history of neoadjuvant (induction) chemotherapy in the definitive surgical management of HNSCC. N Engl J Med. J Clin Oncol (2012) 30(15):1796804. Both trials demonstrated significant benefit for maintenance PARP inhibitors in all subgroups of platinum-sensitive relapsed high-grade serous ovarian cancer. 2016;34(30):363847. 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. PR reports personal fees (honoraria for lectures and Advisory Board Member) from Novartis, BMS, Roche, MSD, GSK, Pfizer, and Amgen outside the submitted work. BMC Medicine Finally, we recently reported a second cohort of our neoadjuvant pembrolizumab trial where instead of one dose, patients received two doses of drug similar to the neoadjuvant phase of the KEYNOTE-689 Phase II trial (75). Pignon J-P, et al. 2017;15:55. In neoadjuvant breast cancer, the I-SPY 1 and 2 trials have successfully matched treatment and biomarkers, using adaptive randomised designs [43, 44]. He has participated in several investigator-driven trials in melanoma and sarcoma. Overall, only 15-20% of patients ultimately benefit from anti-PD-1 in these studies highlighting the need for improving efficacy of CPIs for HNSCC treatment. 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. In support of this, neoadjuvant anti-PD-1 treatment in a mouse HNSCC model resulted in conversion of functional immune-dominance and induced robust anti-cancer responses, supporting the application of neoadjuvant immunotherapy for HNSCC (38). Sholl LM. CAS doi: 10.1056/NEJMoa032641, 8. doi: 10.1038/nature12477, 51. examined neoadjuvant 1) nivolumab (N) or 2) nivolumab plus ipilimumab (N+I) in untreated 29 oral cavity cancer patients in a phase II trial (eligible for T2 or node positive) (NCT02919683) (68). Exclusive: combination of drugs causes tumours to vanish in some terminally ill patients, study finds A new cancer treatment can wipe out tumours in terminally ill head and neck cancer patients, scientists have discovered. Landmark results include those in triple negative breast cancer for the combination of velaparib and carboplatin [44] and neratinib in HER2-positive breast cancer [45]. 2014;32:273543. Forastiere A, et al. Bossi P, Lo Vullo S, Guzzo M, Mariani L, Granata R, Orlandi E, et al. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer. 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. Pathological Response and Survival With Neoadjuvant Therapy in Melanoma: A Pooled Analysis From the International Neoadjuvant Melanoma Consortium (INMC). Our doctors are running clinical trials testing: new drug therapies for head and neck cancer, including immunotherapies and targeted therapies, that can boost the effectiveness of your care. 2016;53:12534. 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. This enhanced function acts to destroy micro-metastasis in clinically advanced tumors, decreasing loco-regional or distant metastasis after primary therapies. A. Rare Driver Mutations in Head and Neck Squamous Cell Carcinomas Converge on NOTCH Signaling. 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 [2], and head and neck cancer [6]. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Mller KM. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. Br J Cancer. doi: 10.1093/annonc/mdy218, 59. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. 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. 2017;15(4):50435. Recent developments in the classification of STS, insights into their molecular pathogenesis and the optimal treatment strategies have evolved considerably during the past decades and have led to the introduction of new therapies. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. In: Proceedings from the American Association for Cancer Research Annual Meeting, April 25, 2017, Washington DC. J Clin Oncol (2013) 31(6):74451. Delay to Surgery After Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Affects Oncologic Outcomes. However, a potential setback is represented by the control arm since chlorambucil is no longer regarded an adequate therapy in CLL [26]. 1998;16:13107. Patients also received 6 months of adjuvant nivolumab and lirilumab. The Society for Immunotherapy of Cancer Consensus Statement on Immunotherapy for the Treatment of Squamous Cell Carcinoma of the Head and Neck (HNSCC). 2016;17(6):791800. 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. Google Scholar. Radiother Oncol (2009) 92(1):414. Google Scholar. Di Veroli GY, Fornari C, Wang D, Mollard S, Bramhall JL, Richards FM, Jodrell DI. BMC Med. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. First published on Mon 11 Oct 2021 07.19 EDT. doi: 10.1158/2159-8290.CD-16-0577, 38. Article quantification of plasma epstein-barr virus DNA in patients with advanced nasopharyngeal carcinoma. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Treatment intensification with neoadjuvant (induction) chemotherapies with platinum drugs are insufficient to significantly prolong overall survival. Immune checkpoint blockade therapies, especially anti-PD-1 and anti-CTLA4, were first approved in advanced melanoma patients (29) and then applied for various cancers (30), which has dramatically impacted the cancer treatment algorithm. Expert Rev Hematol. Using a primary radiation based approach, several ongoing clinical trials aim to de-intensify the treatment impact by adding immunotherapy (77). Int J Radiat Oncol Biol Phys. The significant impact of checkpoint inhibitor therapy for R/M HNSCC has proven the existence of anti-cancer immunity in HNSCC (1214). Cohen EEW, Soulires D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. HS: writing original draft, tables, and figure. Several landmark trials established the clinical benefit of using cisplatin-based chemoradiotherapy after surgery for locally advanced, high-risk HNSCC patients (3, 4). The Checkmate 358 phase I/II study examined clinical safety and efficacy of two doses of neoadjuvant nivolumab in HPV positive or negative HNSCC (NCT02488759) (67). doi: 10.1016/S1470-2045(10)70017-6, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer. This is a preview of subscription content, access via your institution. 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. Int J Radiat Oncol Biol Phys (1992) 23(4):70513. doi: 10.1056/NEJMoa1801946, 48. Several landmark trials established the clinical benefit of using cisplatin-based chemoradiotherapy after surgery for locally advanced, . Lancet. 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. Rochester, Minn., Jacksonville, Fla. This trial aims to enroll 600 patients. HS received funding from the Uehara Foundation (201941070). Notably, grade 3/4 serious adverse events or delay of surgery didnt occur, underscoring the safety of neoadjuvant immunotherapy. 2014;89(1):1320. These included oral mucositis and one patient with autoimmune diabetes (68) and there were no surgical delays. He has published more than 180 peer-reviewed papers primarily in the field of CLL and CLL-related disorders. 2015;372(8):72434. 11:727433. doi: 10.3389/fonc.2021.727433. More effective and cost-efficient phase II trial designs would rapidly lead to landmark trials and practice-changing results. J Clin Oncol. No new safety signals were observed and there were no surgical delays. PubMedGoogle Scholar. Gillison ML, et al. Laramore GE, Scott CB, al-Sarraf M, Haselow RE, Ervin TJ, Wheeler R, et al. 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. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Pembrolizumab versus ipilimumab in advanced melanoma. Ferris RL, Spanos WC, Leidner R, Gonalves A, Martens UM, Kyi C, et al. As mentioned above, to date neoadjuvant immunotherapy has been shown to be safe and has not resulted in surgical delays. 2016;375(22):215464. doi: 10.1016/S0140-6736(18)31999-8, 14. Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes. Induction Chemotherapy Followed by Concurrent Chemoradiotherapy (Sequential Chemoradiotherapy) Versus Concurrent Chemoradiotherapy Alone in Locally Advanced Head and Neck Cancer (PARADIGM): A Randomised Phase 3 Trial. Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect. 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). Menzies AM, Amaria RN, Rozeman EA, Huang AC, Tetzlaff MT, van de Wiel BA, et al. Ann Oncol (2014) 25(1):21625. Springer Nature. 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. Atezolizumab versus docetaxel for patients with previously treated nonsmall-cell lung cancer (POPLAR): a multicentre, open label, phase 2 randomised controlled trial. The checkmate 141 phase III trial evaluated the effect of anti-PD-1 (nivolumab) for R/M HNSCC patients (12). Patients with high-TMB have more effective clinical responses with improved survival in lung, bladder, and head and neck cancer patients (47, 48). There are three major potential benefits to use CPIs in the neoadjuvant setting. defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501). doi: 10.1038/s41591-020-0805-8, 36. doi: 10.1200/JCO.2013.54.6309, 21. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, et al. 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 . Tumour Regression in Non-Small-Cell Lung Cancer Following Neoadjuvant Therapy. Article The Neoadjuvant Immuno-RadioTherapy (NIRT) phase Ib trial tested neoadjuvant stereotactic body radiation therapy (SBRT) with nivolumab (240 mg, q2 weeks x 3) prior to surgery in HNSCC patients (NCT03247712) (66). Filter this list of studies by location, status and more. The Department of Veterans Affairs Laryngeal Cancer Study Group. Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. 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). Neoadjuvant Immunotherapy Leads to Pathological Responses in MMR-Proficient and MMR-Deficient Early-Stage Colon Cancers. The primary endpoint of this trial was comparison between arms of a change in the CD8+ tumor infiltrating lymphocyte (TIL) density. doi: 10.1016/S1470-2045(13)70334-6, 64. The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. 2016;14:20. This diverse patient selection has been used primarily to define a signal of activity. In this trial, pembrolizumab monotherapy significantly improved the OS of PD-L1 positive (CPS 20 or CPS 1) HNSCC. Szturz P, Vermorken JB. Hitt R, Grau JJ, Lpez-Pousa A, Berrocal A, Garca-Girn C, Irigoyen A, et al. Furthermore, tertiary lymphoid structures (TLS) in the tumor bed are suggested tocontribute favorable outcome (55). Readers are encouraged to refer to the full manuscript of these trials for a greater understanding. We defined pathological tumor response (pTR) as one such approach which is quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cell/histiocytic reaction were distinct from growing tumor and only seen after therapy (Figure1). 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). Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. 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. 2023 Springer Nature Switzerland AG. 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. NEngl J Med (2016) 375(19):185667. J Natl Compr Canc Netw. Induction Chemotherapy in Advanced Head and Neck Tumors. Conventional HNSCC is mainly caused by habitual alcohol drinking and smoking, and often occurs in older adults, while human papillomavirus (HPV)-related HNSCC of the oropharyngeal region is rapidly increasing in relatively younger patients (1). Programmed Death-1/Programmed Death-Ligand 1-Axis Blockade in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Stratified by Human Papillomavirus Status: A Systematic Review and Meta-Analysis. 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 . doi: 10.1093/annonc/mdy507, 41. N Engl J Med. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. 14 Articles, This article is part of the Research Topic, Rationale of Neoadjuvant Immunotherapy for HNSCC, Patient Selection for Neoadjuvant Immunotherapy, Biomarker Candidates for Neoadjuvant Immunotherapy, Pathologic Response Criteria for Neoadjuvant Immunotherapy, Clinical Studies of Neoadjuvant Immunotherapy for HNSCC, Immune Related Adverse Events in Neoadjuvant Immunotherapy Treated Patients, Creative Commons Attribution License (CC BY). Clin Pharmacol Ther. Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. statement and Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. In the phase I setting, there is a pressing need to develop better trial methodologies for novel combinations, often of a standard chemotherapy with a novel targeted agent. Lancet (2014) 384(9938):16472. CrossRef The immunological responses were analyzed using blood before and after treatment. doi: 10.1200/JCO.2021.39.15_suppl.6008, 76. 2006;64(1):4756. Am Soc Clin Oncol Educ Book (2020) 40:113. CrossRef For example, radiological tumor examination is widely used in Response Evaluation Criteria In Solid Tumors (RECIST) after organ preservation therapy including radiotherapy and chemotherapy. 2017;5(10):42532. JClin Oncol (2018) 36(31):307783. 2015;385(9980):187383. Lancet (2019) 394(10212):191528. Bertrand Baujat et al. Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients With Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck. A literature review using Medline, Scopus, Google Scholar, the Cochrane Database of Systematic Reviews and the Cochrane cen 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). 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. HE has received research funding from Cancer Research UK and the NIHR HTA, and is funded by the NIHR Cambridge Biomedical Research Centre. doi: 10.1200/JCO.2011.38.8595, 60. doi: 10.1126/science.1208130, 12. Redman JM, Gibney GT, Atkins MB. Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Table2 Ongoing neoadjuvant immunotherapy clinical trials. Epidemiology. Lancet Oncol. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. J Clin Oncol (2021) 39(15_suppl):60533. PubMed Central doi: 10.1016/0360-3016(92)90642-U, 4. In conclusion, we provided here an overview of the history of neoadjuvant immunotherapies in HNSCC starting with chemotherapy extending to exciting frontiers using immunotherapy. In addition, the dynamic expression change of PD-L1 with tumor heterogeneity also makes it difficult to evaluate the expression of PD-L1 (41). Wise-Draper TM, Takiar V, Mierzwa ML, Casper K, Palackdharry S, Worden FP, et al. 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]. The combinatorial therapy group did not significantly increase the CD8+ TILs. 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 . Status: Open - Recruiting. 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). These early studies led to two randomized Phase III trials, which provided Level 1 evidence supporting the use of concurrent chemoradiotherapy in high-risk HNSCC patients (57). Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. N Engl J Med (2018) 378(21):197686. Additionally, R/M HNSCC patients treated with pembrolizumab plus chemotherapy had significantly prolonged OS compared to the cetuximab with chemotherapy group. Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer. N Engl J Med. doi: 10.1016/S0140-6736(13)62422-8, 61. Safety and Tumor Responses With Lambrolizumab (Anti-PD-1) in Melanoma. This trial included both definitive and salvage surgery patients. 2016;387(10028):162937. doi: 10.1158/1078-0432.CCR-19-3977, 71. Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label Randomized Clinical Trial. 2015;373:162739. doi: 10.1200/JCO.2012.43.8820, 28. Indeed, BATTLE, a landmark phase II trial using an adaptive randomised design, tested four novel drugs and biomarker pairings in NSCLC [41]. DCruz A, et al. Cancer Discov. The Mutational Landscape of Head and Neck Squamous Cell Carcinoma. 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. volume15, Articlenumber:111 (2017) doi: 10.1126/science.aax0902, 10. Another topic featured in this article collection is systemic therapy in STS [5], which is a heterogeneous group of rare solid tumours. A clinical trial studying the side effects of chemotherapy for patients with locally recurrent head and neck squamous cell carcinoma. N Engl J Med. doi: 10.1093/annonc/mdt555, 29. 2016;128(24):27703. His current research is focused on investigating the impact of novel laboratory parameters for assessing prognosis of CLL. Wang J, Sun H, Zeng Q, Guo XJ, Wang H, Liu HH, et al. Oliva M, Spreafico A, Taberna M, Alemany L, Coburn B, Mesia R, et al. Science (2011) 333(6046):115760. Rutkowski P, Kozak K. News from the melanoma sessions of the European Cancer Congress 2017. Preoperative Chemotherapy in Advanced Resectable OCSCC: Long-Term Results of a Randomized Phase III Trial. Further, a trial comparing ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab finished recruiting, but results are not yet mature (ClinicalTrials.gov Identifier: NCT02264574). Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, et al. J Clin Oncol (2019) 37(15_suppl):25755. Lancet Oncol (2014) 15(1):e4250. 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. Di Veroli et al. It has become clear that neoadjuvant immunotherapy, especially checkpoint inhibitors, are safe and have shown signals of clinical efficacy in HNSCC. 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. To determine the survival benefit of IC using docetaxel plus cisplatin and fluorouracil (TPF) regimen followed by CCRT, two-phase III randomized trials were completed: the PARADIGM trial reported in 2013 (19) and DeCIDE trial reported in 2014 (20). 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. 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. 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). Enhanced Pathologic Tumor Response With Two Cycles of Neoadjuvant Pembrolizumab in Surgically Resectable, Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC). Received: 18 June 2021; Accepted: 19 August 2021;Published: 06 September 2021. In the KEYNOTE-055 phase II trial, the response rate to pembrolizumab was 22% for p16 positive patients and 16% for p16 negative patients (44). 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. Article To be eligible, patients had to have N2 or N3 adenopathy. In the era of precision cancer medicine, innovative trial designs will also require the matching of novel drugs with putative targets. doi: 10.1158/1078-0432.CCR-16-1761, 43. Lancet. Blood. doi: 10.1200/JCO.2003.06.146, 27. Clin Cancer Res (2020) 26(3):67989. Molica S. Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future. Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, et al. HPV infection might also be a clinical biomarker to predict the response to CPIs. Lancet Oncol. The November 3, 2021 "Clinical Trial Endpoint Development" (12pm - 5:00 pm ET) will address Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) doi: 10.1001/jamaoncol.2020.2955, 69. Neoadjuvant Checkpoint Blockade for Cancer Immunotherapy. Nature (2014) 515(7528):57781. Thus, further studies are needed to define the role of TMB as a predictive biomarker. 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.
