Moreover, recent trials of immune checkpoint inhibitors in melanoma, non-small cell lung carcinoma, and head and neck cancers have significantly influenced the therapeutic landscape by providing promising evidence for immunotherapy efficacy in the adjuvant setting in high-risk locoregional disease. HNSCC shows a relatively high tumor-mutational burden (TMB) (16) and immune infiltration (17), consistent with a potential to achieve therapeutic efficacy from cancer immunotherapy. J Clin Oncol (2021) 39(15_suppl):60533. Pathological Response and Survival With Neoadjuvant Therapy in Melanoma: A Pooled Analysis From the International Neoadjuvant Melanoma Consortium (INMC). doi: 10.1093/annonc/mdt555, 29. Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. doi: 10.1016/0360-3016(92)90027-F, 19. 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. . Herbst RS, Baas P, Kim DW, Felip E, Prez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro Jr G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. 2016;387(10028):162937. N Engl J Med. PR is an active member of the EORTC Soft Tissue and Bone Sarcoma Group, where he chaired the Local Treatment Subcommittee and the Membership Committee of the EORTC Board. We reported a phase II trial, in which neoadjuvant/adjuvant pembrolizumab was tested in locally advanced, resectable HPV-negative HNSCC patients (NCT02296684) (54). safer and more-effective approaches to head and neck radiation therapy. There are three major potential benefits to use CPIs in the neoadjuvant setting. J Clin Oncol (2017) 35(14):15429. doi: 10.1200/EDBK_280687, Keywords: head and neck squamous cell carcinoma, neoadjuvant immunotherapy, clinical trial, biomarker, pathological tumor response, Citation: Shibata H, Saito S and Uppaluri R (2021) Immunotherapy for Head and Neck Cancer: A Paradigm Shift From Induction Chemotherapy to Neoadjuvant Immunotherapy. JClin Oncol (2018) 36(31):307783. Patients also received 6 months of adjuvant nivolumab and lirilumab. PubMed Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. Neoadjuvant Checkpoint Blockade for Cancer Immunotherapy. doi: 10.1126/science.aax0902, 10. Pathological complete response (pCR) and major pathologic response (MPR) are widely used as surrogate clinical endpoints for long-term survival (5962). Lancet Oncol. 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. doi: 10.1038/s41591-020-0805-8, 36. Wason JMS, Abraham JE, Baird RD, Gounaris I, Vallier A-V, Brenton JD, Earl HM, Mander AP. The expression level of PD-L1 in the tumor does not necessarily correlate withthe response to CPIs. Notably, the timing of immune checkpoint inhibitors may influence the outcome of cancer treatment (33). radiotherapy for early glottic carcinoma (T1N0M): results of prospective randomized study of radiation fraction size and overall treatment time. Lancet Oncol. doi: 10.1001/jamaoncol.2020.2955, 69. Combenefit: an interactive platform for the analysis and visualization of drug combinations. Google Scholar. 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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. J Clin Oncol. Burtness B, Harrington KJ, Greil R, Soulires D, Tahara M, de Castro G Jr, et al. N Engl J Med. on behalf of the MAC-NPC Collaborative Group. doi: 10.1093/annonc/mdt461, 25. Second, in contrast to conventional chemotherapy, immunotherapy is much better tolerated by patients. doi: 10.1056/NEJM199106133242402, 23. As mentioned above, to date neoadjuvant immunotherapy has been shown to be safe and has not resulted in surgical delays. Several landmark trials established the clinical benefit of using cisplatin-based chemoradiotherapy after surgery for locally advanced, . Mol Cancer Ther (2017) 16(11):2598608. Junker K, Thomas M, Schulmann K, Klinke F, Bosse U, Mller KM. Nat Commun (2021) 12(1):3349. doi: 10.1038/s41467-021-23355-x, 56. PR reports personal fees (honoraria for lectures and Advisory Board Member) from Novartis, BMS, Roche, MSD, GSK, Pfizer, and Amgen outside the submitted work. 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. Pathologic responses were evaluated in 34 patients (17 HPV+ and 17 HPV-negative). Future Sci OA (2016) 2(1):Fso88. 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. A summary of recent pivotal trials for systemic therapy in advanced STS is presented in Table2 [19,20,21,22]. The pTR rate is calculated as the area of regions 1-3/(1-3)+area of any remaining tumor. J Clin Oncol (2019) 37(15_suppl):25755. Google Scholar. The probability of response to CPIs has at least in part been linked to TMB across cancer types, including HNSCC (16). 2011;12(2):1539. Results from the CLEOPATRA trial in the metastatic setting of the same treatment have produced remarkable results [25]; the same combination produced a 56.5-month median OS compared with 40.8months achieved with trastuzumab and docetaxel alone, showing an increase of 15.7months to OS in the pertuzumab group. Cottrell TR, Thompson ED, Forde PM, Stein JE, Duffield AS, Anagnostou V, et al. Part of Springer Nature. 2006;64(1):4756. Immune cells phenotypes in TME may also be important topredict the response to CPIs. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. 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. Radiother Oncol. 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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. doi: 10.1007/BF01192200, 63. These patients have the worst prognosis despite multimodality approaches and may benefit from neoadjuvant/adjuvant immunotherapy. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al. Zuur CL, Elbers JBW, Vos JL, Avd L, Qiao X, Karakullukcu B, et al. Xu Y, Zhu G, Maroun CA, Wu IXY, Huang D, Seiwert TY, et al. 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. 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]. 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. Lancet. Google Scholar. doi: 10.1056/NEJMoa032641, 8. This was nearly double what we saw with one dose of pembrolizumab. A Randomized Phase III Trial Comparing Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone as Treatment of Unresectable Head and Neck Cancer. The landmark oncology trials highlighted in the BMC Medicine series Spotlight on landmark oncology trials and this editorial are recent trials that have produced practice-changing results for patients. 2016;14(4):45073. J Clin Oncol. Pignon J-P, 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]. Induction Chemotherapy in Advanced Head and Neck Tumors. Novel trial designs could potentially lead to a different type of landmark trial that would accelerate the process and allow cancer patients to access new treatments faster. building alaska cast member dies, peabody news police log,