Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens. 2016;375(1):1122. 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. These included oral mucositis and one patient with autoimmune diabetes (68) and there were no surgical delays. 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). 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. 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. Landmark Trials in Selected Head and Neck Cancers. Cancer Discov. In this trial, primary endpoints are rate of major pathological response (10% tumor cells in resected primary and lymph nodes on central review) and event-free survival (EFS). J Clin Oncol. 2009;92:414. Recent landmark trials in HER2-positive breast cancer include those using dual HER2-targeted therapy pertuzumab and trastuzumab with docetaxel. Nature (2013) 502(7471):3339. N Engl J Med (1991) 324(24):168590. 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). N Engl J Med. To be eligible, patients had to have N2 or N3 adenopathy. 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). Science (2020) 367(6483):12649. Schoenfeld etal. 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). Springer Nature. It remains the fifth leading cause of cancer in the United States and constitutes 10% or more of all cancers worldwide. Google Scholar. Induction Chemotherapy Plus Radiation Compared With Surgery Plus Radiation in Patients With Advanced Laryngeal Cancer. Contact: Elizabeth Akoth, 240-858-3154. However, a potential setback is represented by the control arm since chlorambucil is no longer regarded an adequate therapy in CLL [26]. There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. 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). J Clin Oncol. 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. J Clin Oncol (2021) 39(15_suppl):60533. The era of precision medicine has led to significant developments in the therapy of advanced soft tissue sarcomas (STS), breast cancer, ovarian cancer and haematological neoplasms, among others. The published and ongoing trials described above focused on single agent checkpoint blockade immunotherapy prior to surgery. Weissferdt A, Pataer A, Vaporciyan AA, Correa AM, Sepesi B, Moran CA, et al. 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). These data together support further investigation in Phase III trials such as KEYNOTE-689 to define evidence for survival benefit and identify high-risk patients who may benefit from this approach. Although this study didnt report pathologic responses or clinical efficacy, the proportion of CD8+ T cells, especially granzyme B positive cells, increased after treatment. Recent clinical trials of neoadjuvant immunotherapy show promising results and this methodology has the potential to change the treatment algorithm of HNSCC. All authors read and approved the final manuscript. Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, et al. Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, et al. Table1 Completed neoadjuvant immunotherapy clinical trials. Cancer Discov (2016) 6(12):138299. doi: 10.1158/1078-0432.CCR-19-2209, 39. 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. doi: 10.1200/JCO.2019.37.15_suppl.TPS6090, 77. More effective and cost-efficient phase II trial designs would rapidly lead to landmark trials and practice-changing results. 2017;5(10):42532. Gillison ML, et al. Turner NC, Ro J, Andr F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M, PALOMA3 Study Group. However, the five-year survival rate is still below 50% in advanced HPV-negative HNSCC patients (8), and many patients suffer from severe impact on essential functions. However, translational research did not discover any predictive biomarker subgroups [27] for the palbociclib effect. 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. Lin J-C, et al. BMC Med. Three HPV-positive tumors and one HPV-negative tumor had partial pathologic responses. Improved Efficacy of Neoadjuvant Compared to Adjuvant Immunotherapy to Eradicate Metastatic Disease. 2016;387:154050. doi: 10.1016/j.cllc.2019.11.003, 62. Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, et al. Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J, et al. doi: 10.1056/NEJMoa032646, 6. These successes have led to checkpoint blockade therapies being testing in earlier treatment settings. N Engl J Med. A Study to Evaluate Fractionated Radiation Therapy Utilizing GRID Therapy for Locally-advanced Bulky Tumors. is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer. He works very closely with national patient advocacy groups for GIST and sarcoma and is Chairman of the Melanoma Academy in Poland. Ugurel S, Roehmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, Larkin J, Long GV, Lorigan P, McArthur GA, Ribas A, Robert C, Schadendorf D, Garbe C. Survival of patient s with advanced metastatic melanoma: the impact of novel therapies. 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. Abstract. J Clin Oncol (2019) 37(15_suppl):25755. 2014;32(12):123641. 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: 10.1007/BF01192200, 63. Forastiere A, et al. 2015;372(8):72434. Several landmark trials established the clinical benefit of using cisplatin-based chemoradiotherapy after surgery for locally advanced, high-risk HNSCC patients (3, 4). However, although IC may help with surgical management, Phase III trial results showed no improvements in survival. Clin Lung Cancer (2020) 21(4):3418. Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS. 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. 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. A meta-analysis which examined the results of clinical trials including Checkmate 141, KEYNOTE-012, KEYNOTE-055 showed that HPV infection status was associated with the response rate to anti-PD-1 treatment independently of PD-L1 expression and TMB in HNSCC (45). Palbociclib in hormone-receptor-positive advanced breast cancer. Radiother Oncol. There are now numerous studies introducing neoadjuvant immunotherapy in diverse cancer types (3436). HPV-Associated Head and Neck Cancer: A Virus-Related Cancer Epidemic. Int J Radiat Oncol Biol Phys. Radiation Oncology Consultants (ROC), Chicago, IL, USA, You can also search for this author in 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 . Part of Springer Nature. Nivolumab Plus Ipilimumab in Lung Cancer With a High Tumor Mutational Burden. doi: 10.1126/science.aax0902, 10. The probability of response to CPIs has at least in part been linked to TMB across cancer types, including HNSCC (16). 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. 2017;15(4):50435. 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). J Clin Oncol. Ruffin AT, Cillo AR, Tabib T, Liu A, Onkar S, Kunning SR, et al. 20 studies in Head and Neck Cancer Center (open studies only). In neoadjuvant breast cancer, the I-SPY 1 and 2 trials have successfully matched treatment and biomarkers, using adaptive randomised designs [43, 44]. In addition, adaptive designs for phase I combinations are being developed [40]. 2012;31:84552. 2015;385(9980):187383. Lancet Oncol (2014) 15(1):e4250. 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. With the positive responses in the R/M HNSCC setting, several trials have reported results with neoadjuvant checkpoint immunotherapy prior to surgery (Table1). 2016;35:4907. Clin Cancer Res (2017) 23(12):315867. radiotherapy for early glottic carcinoma (T1N0M): results of prospective randomized study of radiation fraction size and overall treatment time. Treatment intensification with neoadjuvant (induction) chemotherapies with platinum drugs are insufficient to significantly prolong overall survival. doi: 10.1126/science.aax0182, 35. A total of 36 patients (T3/T4; 80%, stage IV; 92%) were enrolled and received one time dose of neoadjuvant pembrolizumab (200 mg) followed by surgery two or three weeks after the immunotherapy. . Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al. Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. doi: 10.1136/jitc-2021-002485, 67. We and others have focused on HPV-negative, locally advanced disease patients with high-risk pathologic features (positive surgical margins or extra-nodal extension). Pan-Tumor Genomic Biomarkers for PD-1 Checkpoint Blockade-Based Immunotherapy. Front. Lancet Oncol. Manage cookies/Do not sell my data we use in the preference centre.

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