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. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Terms and Conditions, Further clinical trials are under way to determine how best to integrate combination immunotherapy and other treatment modalities as well as to establish the correct sequence of therapy with targeted treatment in BRAF-mutated cases. Table1 Completed neoadjuvant immunotherapy clinical trials. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non-Small-Cell Lung Cancer. 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). Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer. Nivolumab (3 mg/kg) was administered on weeks 1 and 3, while ipilimumab (1 mg/kg) was given on week 1 only. 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. Cohen E, 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). Notably, any pTR after neoadjuvant pembrolizumab correlated with baseline tumor PD-L1, immune infiltration, and IFN- activity, but not TMB. Any pTR was seen in 44% and pTR-2 was seen in 22% of patients. 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. J Clin Oncol (2003) 21(2):32733. Radiother Oncol (2009) 92(1):414. doi: 10.1200/JCO.2021.39.15_suppl.6008, 76. 1991;324:168590. 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. Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. 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). 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. 2016;34(30):363847. 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. Google Scholar. Tumour Regression in Non-Small-Cell Lung Cancer Following Neoadjuvant Therapy. Clinical Trial Endpoint Development for Locally Advanced Head and Neck RU serves on an advisory board for Merck, Inc. 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). Pathological Response and Survival With Neoadjuvant Therapy in Melanoma: A Pooled Analysis From the International Neoadjuvant Melanoma Consortium (INMC). 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. doi: 10.1001/jamaoncol.2020.2955, 69. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. These included oral mucositis and one patient with autoimmune diabetes (68) and there were no surgical delays. There were excellent clinical outcomes and only one patient required adjuvant chemoradiation. Nature (2014) 515(7528):57781. doi: 10.1038/nature12634, 50. N Engl J Med. By using this website, you agree to our Neoadjuvant Nivolumab for Patients With Resectable HPV-Positive and HPV-Negative Squamous Cell Carcinomas of the Head and Neck in the CheckMate 358 Trial. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck. HS received funding from the Uehara Foundation (201941070). 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). Compared to our initial cohort with one dose, we found that 50% of patients had any pTR and 44% of patients exhibited pTR2. Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, 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. 2013;10(5):27788. A summary of recent pivotal trials for systemic therapy in advanced STS is presented in Table2 [19,20,21,22]. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. On the other hand, MPR represents 10% of residual viable tumor (63). Rutkowski P, Kozak K. News from the melanoma sessions of the European Cancer Congress 2017. Article doi: 10.1200/JCO.2003.06.146, 27. Menzies AM, Amaria RN, Rozeman EA, Huang AC, Tetzlaff MT, van de Wiel BA, et al. doi: 10.1056/NEJMoa032641, 8. Radiother Oncol. doi: 10.1158/1078-0432.CCR-16-1761, 43. 2010;11:218. Uppaluri R, Lee NY, Westra W, Cohen EEW, Haddad RI, Temam S, et al. 2016;14(4):45073. Immune Biomarkers of Response to Immune-Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. In fact, meta-analysis of melanoma neoadjuvant immunotherapy trials has shown that any degree of pathologic response and not just MPR/pCR, was correlated with better clinical outcomes (64). doi: 10.1001/jamaoncol.2015.3638, 42. doi: 10.1200/JCO.2019.37.15_suppl.TPS6090, 77. Pembrolizumab versus ipilimumab in advanced melanoma. 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. 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. It is meant to be an educational resource . Larkin J, Chiarion-Sileni V, Gonzalez R, et al. 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. Immunological Effects of Nivolumab Immunotherapy in Patients With Oral Cavity Squamous Cell Carcinoma. There were no treatment related delays thus achieving the primary safety endpoint. doi: 10.1016/S0140-6736(18)31999-8, 14. In: Landmark Trials in Oncology. In addition, there was evidence of response in both arms. doi: 10.4155/fso.15.88, 44. N Engl J Med (2004) 350(19):193744. Recent landmark immunotherapy trials - melanoma, Primary Chemotherapy in Resectable Oral Cavity Squamous Cell Cancer: A Randomized Controlled Trial. Clin Cancer Res (2020) 26(19):514052. Combenefit: an interactive platform for the analysis and visualization of drug combinations. Cancer Discov (2016) 6(12):138299. Differences in T-Cell Infiltrates and Survival Between HPV+ and HPV- Oropharyngeal Squamous Cell Carcinoma. 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. chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. All authors contributed to the article and approved the submitted version. Based on this study and depending on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) either pembrolizumab alone or with chemotherapy represents the first choice for these patients (14). He has authored or co-authored over 120 scientific papers in Polish and international journals (with an impact factor of above 1200, index-H: 32, citation index>4000), and is co-author of national and international recommendations for sarcoma and melanoma. 2014;370(12):110110. Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. 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. 2016;128(24):27703. NEngl J Med (2008) 359(11):111627. A phase II trial was reported by Xiong etal. strategies for preserving the quality of life during and after treatment. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. 2016;387(10028):162937. J Clin Oncol. Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F, COMPLEMENT 1 Study Investigators. 2017;15:55. doi: 10.1016/0360-3016(92)90027-F, 19. These data indicate that PD-L1 expression on tumor cells is not a perfect biomarker to predict the clinical outcome. 2017;5(10):42532. Marur S, DSouza G, Westra WH, Forastiere AA. J Clin Oncol (2019) 37(15_suppl):25755. doi: 10.1093/annonc/mdy495, 49. A natural extension of this work has led several groups to test whether neoadjuvant chemotherapy prior to surgery would improve clinical outcomes. It remains the fifth leading cause of cancer in the United States and constitutes 10% or more of all cancers worldwide. Forastiere A, et al. In neoadjuvant breast cancer, the I-SPY 1 and 2 trials have successfully matched treatment and biomarkers, using adaptive randomised designs [43, 44]. These are the first clear data in HNSCC supporting the finding that neoadjuvant anti-PD1 induced PR is a predictor of clinical outcomes. doi: 10.1056/NEJMoa1305133, 30. 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). In this trial, pembrolizumab monotherapy significantly improved the OS of PD-L1 positive (CPS 20 or CPS 1) HNSCC. 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. 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. Lancet Oncol. 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. 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. 2018. 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). doi: 10.1172/jci.insight.89829, 18. Cooper JS. J Clin Oncol. Enhanced Pathologic Tumor Response With Two Cycles of Neoadjuvant Pembrolizumab in Surgically Resectable, Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC). There are several distinct mechanisms of how radiation and/or chemotherapy can work with immunotherapy and other have covered these topics.