Subscribe to RSS
DOI: 10.1055/a-1792-2246
Neue Therapieansätze für Speicheldrüsenmalignome
Novel therapeutic approaches for salivary gland carcinomasZusammenfassung
In den vergangenen Jahren haben sich durch die Verbesserung und Verbreitung molekularpathologischer Testverfahren und die Möglichkeit von zielgerichteten Therapien neue Optionen in der Behandlung von Speicheldrüsenmalignomen ergeben. Durch die neuen zielgerichteten Therapieoptionen werden Patienten deutlich weniger toxische Alternativen zur konventionellen zytostatischen Chemotherapie geboten. Zum einen gibt es neue entitätsspezifische Therapien, wie z.B. die Therapie mit NTRK-Inhibitoren bei sekretorischen Karzinomen und die Therapie mit Axitinib bei adenoidzystischen Karzinomen. Darüber hinaus rücken aber auch entitätsübergreifende Therapeutika, wie z.B. die antiandrogene Therapie, die HER2-Inhibition oder auch die PI3K-Inhibition, in den Vordergrund. Bei metastasierten/rezidivierten Speicheldrüsenkarzinomen, welche nicht mit einer zielgerichteten Therapie behandelt werden können, werden weiterhin hauptsächlich platinbasierte Chemotherapien eingesetzt.
Abstract
Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas. Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice.
Schlüsselwörter
Speicheldrüsenkarzinom - zielgerichtete Therapie - Glandula parotidea - Speicheldrüsen - Chemotherapie - salivary gland carcinoma - targeted therapy - salivary glandPublication History
Received: 08 August 2021
Accepted after revision: 07 March 2022
Article published online:
23 March 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Doescher J, Schuler PJ, Greve J. et al. Maligne Speicheldrüsentumoren – Highlights der ASCO-Jahrestagung 2019. HNO 2019; 67 (12) 931-934 DOI: 10.1007/s00106-019-00760-9. (PMID: 31628530)
- 2 Guzzo M, Locati LD, Prott FJ. et al. Major and minor salivary gland tumors. Critical Reviews in Oncology/Hematology 2010; 74 (02) 134-148 DOI: 10.1016/j.critrevonc.2009.10.004. (PMID: 19939701)
- 3 WHO Classification of Head and Neck Tumours. El-Naggar AK, Chan JKC, Grandis JR. 4th edition. Lyon, France: International Agency for Research on Cancer; 2017
- 4 Ihrler S, Guntinas-Lichius O, Haas C. et al. Neues zu Tumoren der Speicheldrüsen: WHO-Klassifikation 2017. Pathologe 2018; 39 (01) 11-17 DOI: 10.1007/s00292-017-0407-5. (PMID: 29372306)
- 5 Berrino F, De AR, Sant M. et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–1999: results of the EUROCARE-4 study. Lancet Oncol 2007; 8: 773-783
- 6 Meyer MF, Arolt C, Kansy BA. et al. Das Tumormikromilieu bei Speicheldrüsenkarzinomen – mögliche Konsequenzen für neue Therapiekonzepte. HNO 2020; 68 (12) 927-934 DOI: 10.1007/s00106-020-00926-w. (PMID: 32929519)
- 7 Wang X, Luo Y, Li M. et al. Management of salivary gland carcinomas – a review. Oncotarget 2017; 8 (03) 3946-3956 DOI: 10.18632/oncotarget.13952. (PMID: 27992367)
- 8 Chen AM, Bucci MK, Quivey JM. et al. Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas. International Journal of Radiation Oncology Biology Physics 2006; 66 (04) 1044-1050 DOI: 10.1016/j.ijrobp.2006.06.050. (PMID: 16965870)
- 9 Chintakuntlawar AV, Okuno SH, Price KA. Systemic therapy for recurrent or metastatic salivary gland malignancies. Cancers Head Neck 2016; 1 (01) 11 DOI: 10.1186/s41199-016-0011-z. (PMID: 31093341)
- 10 Lagha A, Chraiet N, Ayadi M. et al. Systemic therapy in the management of metastatic or advanced salivary gland cancers. Head Neck Oncol 2012; 4 (01) 19 DOI: 10.1016/j.oraloncology.2018.01.034. (PMID: 29496053)
- 11 Hsieh CE, Lin CY, Lee LY. et al. Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma – a propensity score matched study. Radiation Oncology 2016; 11 (01) DOI: 10.1186/s13014-016-0617-7.
- 12 Alfieri S, Granata R, Bergamini C. et al. Systemic therapy in metastatic salivary gland carcinomas: A pathology-driven paradigm?. Oral Oncology 2017; 66: 58-63 DOI: 10.1016/j.oraloncology.2016.12.016. (PMID: 28249649)
- 13 Stenner M, Molls C, Klußmann JP. et al. Zur Prognose chirurgisch therapierter primärer Parotiskarzinome – eine Untersuchung an 231 Fällen. Laryngo-Rhino-Otol 2011; 90 (11) 664-671
- 14 Trendowski MR, El Charif O, Dinh PC. et al. Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities. Clin Cancer Res 2019; 25 (04) 1147-1155 DOI: 10.1158/1078-0432.CCR-18-2244. (PMID: 30305294)
- 15 Stenner M, Klussmann JP. Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. Eur Arch Otorhinolaryngol 2009; 266 (03) 333-341 DOI: 10.1007/s00405-008-0882-7. (PMID: 19052760)
- 16 Yin LX, Ha PK. Genetic alterations in salivary gland cancers: Salivary Gland Cancers. Cancer 2016; 122 (12) 1822-1831 DOI: 10.1002/cncr.29890. (PMID: 26928905)
- 17 Stenman G. Fusion Oncogenes in Salivary Gland Tumors: Molecular and Clinical Consequences. Head and Neck Pathol 2013; 7 (Suppl. 01) 12-19 DOI: 10.1007/s12105-013-0462-z. (PMID: 23821214)
- 18 Hong DS, DuBois SG, Kummar S. et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. The Lancet Oncology 2020; 21 (04) 531-540 DOI: 10.1016/S1470-2045(19)30856-3. (PMID: 32105622)
- 19 Doebele RC, Drilon A, Paz-Ares L. et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol 2020; 21 (02) 271-282 DOI: 10.1016/S1470-2045(19)30691-6. (PMID: 31838007)
- 20 Hyman D, Kummar S, Farago A. et al. CT-127 – phase I and expanded access experience of LOXO-195 (BAY 2731954), a selective next-generation TRK inhibitor (TRKi). In: Proceedings of the 10th Annual Meeting of the American Association for Cancer Research; 2019. Philadelphia PA: AACR; 2019: 127
- 21 Locati LD, Perrone F, Cortelazzi B. et al. Clinical activity of androgen deprivation therapy in patients with metastatic/relapsed androgen receptor-positive salivary gland cancers: Androgen deprivation therapy in salivary gland cancers. Head Neck 2016; 38 (05) 724-731 DOI: 10.1002/hed.23940. (PMID: 25522335)
- 22 Haddad R, Colevas AD, Krane JF. et al. Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study. Oral Oncol 2003; 39 (07) 724-727 DOI: 10.1016/s1368-8375(03)00097-6. (PMID: 12907212)
- 23 Takahashi H, Tada Y, Saotome T. et al. Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma. J Clin Oncol 2019; 37 (02) 125-134 DOI: 10.1200/JCO.18.00545. (PMID: 30452336)
- 24 Sheth H, Kumar P, Shreenivas A. et al. Excellent Response With Alpelisib and Bicalutamide for Advanced Salivary Duct Carcinoma With PIK3CA Mutation and High Androgen Receptor Expression – A Case Report. JCO Precision Oncology 2021; (05) 744-750 DOI: 10.1200/PO.20.00436. (PMID: 34036229)
- 25 Fayette J, Even C, Digue L. et al. NISCAHN: A phase II, multicenter nonrandomized trial aiming at evaluating nivolumab (N) in two cohorts of patients (pts) with recurrent/metastatic (R/M) salivary gland carcinoma of the head and neck (SGCHN), on behalf of the Unicancer Head & Neck Group. JCO 2019; 37 (Suppl. 15) 6083-6083
- 26 Keam B, Kang EJ, Ahn MJ. et al. Randomized phase II study of axitinib versus observation in patients with recurred or metastatic adenoid cystic carcinoma. Journal of Clinical Oncology 2020; 38 (Suppl. 15) 6503-6503 DOI: 10.1158/1078-0432.CCR-21-1061. (PMID: 34315722)
- 27 Ho AL, Dunn L, Sherman EJ. et al. A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma. Ann Oncol 2016; 27 (10) 1902-1908 DOI: 10.1093/annonc/mdw287. (PMID: 27566443)
- 28 Mimica X, McGill M, Hay A. et al. Distant metastasis of salivary gland cancer: Incidence, management, and outcomes. Cancer 2020; 126 (10) 2153-2162 DOI: 10.1002/cncr.32792. (PMID: 32097509)
- 29 Xu L, Zhao F, Yang W. et al. MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma. International Journal of Oncology 2019; 54 (05) 1579-1590 DOI: 10.3892/ijo.2019.4754. (PMID: 30896785)
- 30 Okumura Y, Miyabe S, Nakayama T. et al. Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma: Mucoepidermoid carcinoma classification. Histopathology 2011; 59: 90-97 DOI: 10.1111/j.1365-2559.2011.03890.x. (PMID: 21668476)
- 31 Luk PP, Wykes J, Selinger CI.. et al. Diagnostic and prognostic utility of Mastermind-like 2 (MAML2) gene rearrangement detection by fluorescent in situ hybridization (FISH) in mucoepidermoid carcinoma of the salivary glands. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 121: 530-541 DOI: 10.1016/j.oooo.2016.01.003. (PMID: 27068311)
- 32 Okumura Y, Murase T, Saida K.. et al. Postoperative radiotherapy for T1/2N0M0 mucoepidermoid carcinoma positive for CRTC1/3-MAML2 fusions. Head Neck 2018; 40: 2565-2573 DOI: 10.1002/hed.24856. (PMID: 30475407)
- 33 Behboudi A, Enlund F, Winnes M.. et al. Molecular classification of mucoepidermoid carcinomas. Prognostic significance of the MECT1–MAML2 fusion oncogene. Genes Chromosomes Cancer 2006; 45: 470-481 DOI: 10.1002/gcc.20306. (PMID: 16444749)
- 34 Chen Z, Chen J, Gu Y. et al. Aberrantly activated AREG–EGFR signaling is required for the growth and survival of CRTC1–MAML2 fusion-positive mucoepidermoid carcinoma cells. Oncogene 2014; 33 (29) 3869-3877 DOI: 10.1038/onc.2013.348. (PMID: 23975434)
- 35 Nachtsheim L, Arolt C, Dreyer T. et al. Das Mukoepidermoidkarzinom – Bedeutung der Molekularpathologie. Laryngo-Rhino-Otol 2020; 99 (03) 144-148 DOI: 10.1055/a-1083-6805. (PMID: 32120437)
- 36 Fushimi C, Tada Y, Takahashi H. et al. A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma. Ann Oncol 2018; 29 (04) 979-984 DOI: 10.1093/annonc/mdx771. (PMID: 29211833)
- 37 Egebjerg K, Harwood CD, Woller NC. et al. HER2 Positivity in Histological Subtypes of Salivary Gland Carcinoma: A Systematic Review and Meta-Analysis. Front Oncol 2021; 11: 693394 DOI: 10.3389/fonc.2021.693394. (PMID: 34249747)
- 38 Sawyers CL. Herceptin: A First Assault on Oncogenes that Launched a Revolution. Cell 2019; 179 (01) 8-12 DOI: 10.1016/j.cell.2019.08.027. (PMID: 31519311)
- 39 Li BT, Shen R, Offin M. et al. Ado-trastuzumab emtansine in patients with HER2 amplified salivary gland cancers (SGCs): Results from a phase II basket trial. JCO 2019; 37 (Suppl. 15) 6001-6001
- 40 Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway?. Nat Rev Clin Oncol 2018; 15 (05) 273-291 DOI: 10.1038/nrclinonc.2018.28. (PMID: 29508857)
- 41 André F, Ciruelos E, Rubovszky G. et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380 (20) 1929-1940 DOI: 10.1056/NEJMoa1813904. (PMID: 31091374)
- 42 Schoenfeld JD, Mahmood U, Chen YH. et al. A randomized phase II study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma. JCO 2019; 37 (Suppl. 15) 6082-6082 DOI: 10.1016/j.ijrobp.2020.08.018. (PMID: 32781104)
- 43 Arolt C, Meyer M, Ruesseler V. et al. Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas. Cancer Immunol Immunother 2020; 69 (07) 1363-1373 DOI: 10.1007/s00262-020-02551-6. (PMID: 32232506)
- 44 Debaere D, Vander Poorten V, Nuyts S. et al. Cyclophosphamide, doxorubicin, and cisplatin in advanced salivary gland cancer. B-ENT 2011; 7 (01) 1-6 (PMID: 21563549)
- 45 Dreyfuss AI, Clark JR, Fallon BG. et al. Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin. Cancer 1987; 60 (12) 2869-2872 DOI: 10.1002/1097-0142(19871215)60:12<2869::aid-cncr2820601203>3.0.co;2-y. (PMID: 2824016)
- 46 Licitra L, Cavina R, Grandi C. et al. Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 1996; 7 (06) 640-642 DOI: 10.1093/oxfordjournals.annonc.a010684. (PMID: 8879381)
- 47 Locati LD, Rinaldi G, Bossi P. et al. Herceptin plus chemotherapy in relapsed and/or metastatic salivary gland cancer. Oral Oncol 2005; 41 (01) 97-98 DOI: 10.1016/j.oraloncology.2004.03.002. (PMID: 15598592)
- 48 Locati LD, Perrone F, Losa M. et al. Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs). Oral Oncology 2009; 45 (11) 986-990 DOI: 10.1016/j.oraloncology.2009.05.635. (PMID: 19574086)
- 49 Skálová A, Vanecek T, Sima R. et al. Mammary Analogue Secretory Carcinoma of Salivary Glands, Containing the ETV6-NTRK3 Fusion Gene: A Hitherto Undescribed Salivary Gland Tumor Entity. American Journal of Surgical Pathology 2010; 34 (05) 599-608 DOI: 10.1097/PAS.0b013e3181d9efcc. (PMID: 20410810)
- 50 Stenzinger A, van Tilburg CM, Tabatabai G. et al. Diagnostik und Therapie von Tumoren mit NTRK-Genfusionen. Pathologe 2021; 42 (01) 103-115 DOI: 10.1007/s00292-020-00864-y. (PMID: 33258061)