Therapie der Weichgewebssarkome inklusive GIST – Update 2021

Was ist neu?

Neoadjuvante und adjuvante Chemotherapie Zur Risikoabschätzung einer perioperativen Chemotherapie kann der „Sarculator“ eingesetzt werden. Unter Einbeziehung von histologischem Subtyp, Tumorgröße, -grading und Patientenalter hilft er, das individuelle Rezidivrisiko zu bestimmen.

Palliative Systemtherapie Zunehmende Hinweise aus Subgruppenanalysen prospektiver Studien und retrospektiven Studien sprechen dafür, dass Patienten mit bestimmten Sarkom-Subtypen auch bezüglich des Gesamtüberlebens von subtypspezifischen Kombinationstherapien schon in der ersten Therapielinie profitieren können. Die Therapieplanung in der metastasierten Situation sollte nicht nur nach patientenindividuellen Gesichtspunkten, sondern auch Sarkom-Subtyp-spezifisch erfolgen.

Gastrointestinaler Stromatumor Mit Avapritinib steht ab sofort eine hochwirksame Therapie für GIST mit der bislang als therapierefraktär angesehenen PDGFRA-Exon-18-D842V-Mutation zur Verfügung. Ripretinib ist eine neue Therapieoption für Patienten, die alle derzeit zugelassenen Substanzen bereits erhalten haben. Durch eine 3-jährige adjuvante Therapie kann bei Patienten mit hohem Rezidivrisiko etwa die Hälfte aller Todesfälle in den ersten 10 Jahren Nachbeobachtung vermieden werden.

Abstract

Soft tissue sarcomas are rare tumors that represent a major challenge due to varying clinical presentations and often interdisciplinary treatment concepts. Gold standard for the treatment of localized resectable soft tissue sarcomas is complete surgical removal. So far, multimodality treatment does not represent a clininal standard. However, several newer analyses and studies suggest that a subgroup of patients seems to derive an overall survival benefit from perioperative chemotherapy. In metastatic soft tissue sarcoma systemic therapy is the treatment of choice. Most active drugs are the anthracyclines and ifosfamide. Combination chemotherapy has improved both response rate and progression-free survival at the costs of increased toxicity in comparison to single agent therapy but without impact on overall survival in first-line therapy. In pretreated patients, treatment options consist of trabectedin, pazopanib, gemcitabine plus docetaxel or DTIC, and eribulin. Recent data have shown that histiotype-specific treatment options including targeted therapy represent a major improvement for several sarcoma subtypes.

In GIST, imatinib is the gold standard for patients with advanced or metastatic disease. In imatinib refractory or intolerant patients, sunitinib in an individualized treatment schedule is recommended. Regorafenib has been approved for third-line therapy. Recently, avapritinib has been approved for treatment of patients with the so far resistant D842V mutation in the PDGFRA exon 18. Ripretinib has shown very promising activity in forth and further lines of therapy and is already approved in the US. The use of adjuvant imatinib therapy in patients with completely resected localized GIST with a high risk of recurrence has significantly improved overall survival with a treatment duration of 3 years. These results have now been confirmed with a 10 years follow-up analysis.

Schlüsselwörter

Weichgewebssarkome - GIST - multimodale Therapie - zielgerichtete Therapie

Key words

soft tissue sarcoma - GIST - multimodalitiy treatment - targeted therapy

Publication History

Article published online:
29 January 2021

• Literatur

• 1 Callegaro D, Miceli R, Bonvalot S. et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 2016; 17: 671-680
• 2 Pasquali S, Pizzamiglio S, Touati N. et al. The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial. Eur J Cancer 2019; 109: 51-60
• 3 Issels RD, Lindner LH, Verweij J. et al. Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial. JAMA Oncol 2018; 4: 483-492
• 4 Tap WD, Wagner AJ, Schöffski P. et al. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA 2020; 323: 1266-1276
• 5 Seddon B, Strauss SJ, Whelan J. et al. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol 2017; 18: 1397-1410
• 6 Young RJ, Litière S, Lia M. et al. Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study. Acta Oncol 2017; 56: 1013-1020
• 7 D’Ambrosio L, Touati N, Blay JY. et al. Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first-line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Cancer 2020; 126: 2637-2647
• 8 Onkopedia. Weichgewebssarkome (maligne Weichgewebstumoren) des Erwachsenen (April 2019). Im Internet (Stand: 23.11.2020): https://www.onkopedia.com/de/onkopedia/guidelines/weichgewebssarkome-maligne-weichgewebstumoren-des-erwachsenen/@@guideline/html/index.html
• 9 Wilky BA, Trucco MM, Subhawong TK. et al. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol 2019; 20: 837-848
• 10 Stacchiotti S, Schoffski P, Jones R. et al. Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients (pts) with epithelioid sarcoma (ES) (NCT02601950). J Clin Oncol 2019; 37 (Suppl. 15) 11003
• 11 Heinrich MC, Jones RL, von Mehren M. et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol 2020; 21: 935-946
• 12 Janku F, Razak ARA, Gordon MS. et al Encouraging activity of novel pan-KIT and PDGFRα inhibitor DCC-2618 in patients (pts) with Gastrointestinal Stromal Tumor (GIST). ESMO 2017; Abstr. 1473O
• 13 Blay JY, Serrano C, Heinrich MC. et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2020; 21: 923-934
• 14 Joensuu H, Eriksson M, Sundby-Hall K. et al. Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors An Analysis of a Randomized Clinical Trial After 10-Year Follow-up. JAMA Oncol 2020; 6 (08) 1241-1246