landmark trials in head and neck cancer ppt landmark trials in head and neck cancer ppt

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. Licitra L, Grandi C, Guzzo M, Mariani L, Lo Vullo S, Valvo F, et al. There were excellent clinical outcomes and only one patient required adjuvant chemoradiation. J Clin Oncol. 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). Cite this article. Lancet. In addition, IC may increase the possibility of severe AEs as compared to CCRT in non-surgical locally, advanced HNSCC treatment. He is also an active member of the EORTC Melanoma Group and the Global Melanoma Task Force. Note that MPR was observed in 8 (29%) patients in either the primary tumor or lymph node metastasis. 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. This was followed by BATTLE-2 [42], testing combination treatments in the same disease. Nat Rev Clin Oncol. The BATTLE-2 Study: a biomarker-integrated targeted therapy study in previously treated patients with advanced nonsmall-cell lung cancer. However, IC remains an attractive approach for specific cases of advanced disease with a high risk for local or distant failure or to debulk rapidly growing tumors (19). Di Veroli GY, Fornari C, Wang D, Mollard S, Bramhall JL, Richards FM, Jodrell DI. 2023 BioMed Central Ltd unless otherwise stated. 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). 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. (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). Squamous cell carcinoma (SCC) is the predominant malignant histology of the mucosal surfaces of the head and neck (HN) region that includes the oral cavity, pharynx, and larynx. Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. In: Landmark Trials in Oncology. Article 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]). Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. TMB is a potential predictive biomarker that also needs further exploration. These included oral mucositis and one patient with autoimmune diabetes (68) and there were no surgical delays. The EORTC 22931 and RTOG 9501 trials were published in 2004 and demonstrated that the addition of concurrent cisplatin chemotherapy to radiation therapy in the postoperative setting improved outcomes for selected (based on pathologic features) patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. The era of precision medicine has led to significant developments in the therapy of advanced soft tissue sarcomas (STS), breast cancer, ovarian cancer and haematological neoplasms, among others. Clin Cancer Res (2020) 26(13):32119. 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). Xiong Y, Neskey DM, Horton JD, Paulos CM, Knochelmann HM, Armeson KE, et al. Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. Table1 Completed neoadjuvant immunotherapy clinical trials. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck. 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. 20 studies in Head and Neck Cancer Center (open studies only). Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR, Tsao A, Stewart DJ, Hicks ME, Erasmus J, Gupta S. The BATTLE trial: personalizing therapy for lung cancer. Schoenfeld etal. PubMedGoogle Scholar, Yajnik, S. (2019). Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. 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. Lancet Oncol. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. 2016;35:4907. Palbociclib in hormone-receptor-positive advanced breast cancer. 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). Nivolumab Plus Ipilimumab in Lung Cancer With a High Tumor Mutational Burden. N Engl J Med. J Clin Oncol. Tumour Regression in Non-Small-Cell Lung Cancer Following Neoadjuvant Therapy. Rochester, Minn., Jacksonville, Fla. on behalf of the MAC-NPC Collaborative Group. 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. HE, SM and PR contributed equally to drafting, editing and revision of the manuscript. Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Corts J, CLEOPATRA Study Group. We and others have focused on HPV-negative, locally advanced disease patients with high-risk pathologic features (positive surgical margins or extra-nodal extension). Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, et al. Int J Radiat Oncol Biol Phys (1996) 36(5):9991004. Cancer (2021) 127(12):198492. Lancet. Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, et al. J Clin Oncol (2021) 39(15_suppl):60066. 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. doi: 10.1001/jamaoncol.2015.3638, 42. J Clin Oncol. Recent landmark trials in HER2-positive breast cancer include those using dual HER2-targeted therapy pertuzumab and trastuzumab with docetaxel. 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. Patients also received 6 months of adjuvant nivolumab and lirilumab. 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. The IMCISION study (NCT03003637) presented at ESMO 2020 is examining neoadjuvant nivolumab and ipilimumab for stage II-IVa HNSCC patients. HE has received research funding from Cancer Research UK and the NIHR HTA, and is funded by the NIHR Cambridge Biomedical Research Centre. A phase II trial was reported by Xiong etal. 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. 2015;113(5):699705. doi: 10.1158/2159-8290.CD-16-0577, 38. Bayesian adaptive designs for biomarker trials with biomarker discovery. HS received funding from the Uehara Foundation (201941070). Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. Timing of Neoadjuvant Immunotherapy in Relation to Surgery Is Crucial for Outcome. Hanna GJ, Lizotte P, Cavanaugh M, Kuo FC, Shivdasani P, Frieden A, et al. Google Scholar. Cancer Discov. Int J Radiat Oncol Biol Phys (1992) 23(3):6712; discussion 6778. Immune Biomarkers of Response to Immune-Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. 2012;366(15):138292. Correspondence to HPV infection might also be a clinical biomarker to predict the response to CPIs. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Notably, four patients (N, n=1; N+I, n=3) had major/complete response (greater than 90%). 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). Laramore GE, Scott CB, al-Sarraf M, Haselow RE, Ervin TJ, Wheeler R, et al. In the KEYNOTE-048 phase III trial, significant survival benefit of pembrolizumab for patients was seen with PD-L1 expression 1% and 20% by CPS (14). Manage cookies/Do not sell my data we use in the preference centre. Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil CM, Lotem M, Larkin JMG, Lorigan P, Neyns B, Blank CU, Petrella TM, Hamid O, Zhou H, Ebbinghaus S, Ibrahim N, Robert C. Pembrolizumab versus ipilimumab for advanced melanoma: Final overall survival analysis of KEYNOTE-006. 2016;387:154050. 2014;14:31723. In this trial, safety, pTR, and relapse rate with pembrolizumab were evaluated. Atezolizumab versus docetaxel for patients with previously treated nonsmall-cell lung cancer (POPLAR): a multicentre, open label, phase 2 randomised controlled trial. 2016;32(18):28668. 2006;64(1):4756. Menzies AM, Amaria RN, Rozeman EA, Huang AC, Tetzlaff MT, van de Wiel BA, et al. Radiation Oncology Consultants (ROC), Chicago, IL, USA, You can also search for this author in 2014;89(1):1320. Saad ED, Paoletti X, Burzykowski T, Buyse M. Precision medicine needs randomized clinical trials. 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. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer. National Cancer Center Hospital East, Japan, University General Hospital Attikon, Greece. doi: 10.1126/science.aar3593, 52. Finally, biomarker and minimal residual disease assessment may ultimately be useful to guide the targeted agent or regimen of choice and the duration of treatment [38]. 2017;15:57. Clinical outcomes were better than historical with 70% 1-year disease free survival and 85% 1-year overall survival. Novel Strategies to Effectively De-Escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions. radiotherapy for early glottic carcinoma (T1N0M): results of prospective randomized study of radiation fraction size and overall treatment time. The goal of cytotoxic chemotherapy in this setting is to directly attack tumor cells to reduce tumor burden. The Annals of Surgical Oncology (ASO) is pleased to announce, The Landmark Series. RU is funded by NIH/NIDCR R01DE024403, R01DE027736, and NIH/NCI/NIDCR U01DE029188. Considering the treatment nave situation and the absence of treatment-resistant cells compared with the R/M setting, neoadjuvant immunotherapy is hypothetically likely able to result in a strong and durable therapeutic effect. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Bioinformatics. 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). Google Scholar. The primary endpoint of this trial was comparison between arms of a change in the CD8+ tumor infiltrating lymphocyte (TIL) density. Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Mller KM. The immunological responses were analyzed using blood before and after treatment. Notably, any pTR after neoadjuvant pembrolizumab correlated with baseline tumor PD-L1, immune infiltration, and IFN- activity, but not TMB. 2014;370(12):110110. 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). Marur S, DSouza G, Westra WH, Forastiere AA. 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/NEJMoa0802656, 33. The RTOG 90-03 trial compared four radiation therapy fractionation schemes for locoregionally advanced patients undergoing radiation therapy alone and is discussed. Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. doi: 10.1016/S1470-2045(10)70017-6, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. N Engl J Med (2013) 369(2):13444. 2010;11:218. 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). 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. Postoperative Irradiation With or Without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer. Nature (2013) 500(7463):41521. High Tumor Mutation Burden Fails to Predict Immune Checkpoint Blockade Response Across All Cancer Types. He was/is member of the editorial board of Leukemia and Lymphoma, BMC Medicine, ISRN Hematology and International Journal of Hematologic Oncology. Beitler J, et al. statement and Lancet Oncol (2010) 11(8):7819. Lancet Oncol. HPV-related oropharyngeal HNSCC shows better survival related to HPV-negative oropharyngeal HNSCCs. N Engl J Med (2018) 378(22):2093104. Delay to Surgery After Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Affects Oncologic Outcomes. Blood. 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. 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. Tumors with both PD-L1 and PD-L2 expression responded better than tumors with only PD-L1 expression, indicating that combinatorial scoring may be an attractive approach. Adjuvant Chemotherapy for Resectable Squamous Cell Carcinomas of the Head and Neck: Report on Intergroup Study 0034. 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. BMC Medicine 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. reported on findings from a clinical trial where neoadjuvant nivolumab (240 mg on days 1 and 15) with or without tadalafil was tested. 2014;32:294050. Kwok M, Rawstron AC, Varghese A, Evans PA, OConnor SJ, Doughty C, Newton DJ, Moreton P, Hillmen P. Minimal residual disease is an independent predictor for 10-year survival in CLL. Nevertheless, the selection of systemic therapy must be strictly individualised and based upon several factors, including the histology and biological behaviour of the disease. In addition to radiation and immunotherapy combinations, other trials are testing chemotherapy/immunotherapy combinations. 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. DCruz A, et al. Management of toxicities in this setting remains a challenge. doi: 10.1200/JCO.2011.38.8595, 60. 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). doi: 10.1056/NEJMoa1716078, 37. 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. BMC Med. SM currently serves as referee for several haematology and oncology journals such as Journal Clinical Oncology, Blood, Haematologica, Leukemia Research, Leukemia, Leukemia & Lymphoma, European Journal Haematology, Cancer, British Journal of Haematology, and Lancet Haematology. To be eligible, patients had to have N2 or N3 adenopathy.