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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Oncology

Systemic & Targeted Therapies

At a Glance

Systemic treatments for soft tissue sarcoma (STS) vary widely by subtype. Traditional chemotherapy is commonly used for sarcomas like leiomyosarcoma, while gastrointestinal stromal tumors (GIST) require targeted therapies. Immunotherapy is emerging as a strong option for rare subtypes like ASPS.

When a cancer is “systemic,” it means it has the potential to travel through the bloodstream to other parts of the body. Systemic therapy uses medications to find and destroy these cancer cells wherever they may be. In the world of soft tissue sarcoma (STS), there is no “one-size-fits-all” treatment; the medications used are highly dependent on your specific subtype [1][2].

Traditional Chemotherapy

The “backbone” of treatment for many advanced sarcomas—especially Leiomyosarcoma (LMS) and Synovial Sarcoma—remains traditional chemotherapy.

  1. Doxorubicin (Anthracycline): Often the first-line treatment for metastatic STS. While effective for many subtypes, it carries a risk of cardiotoxicity (heart damage), so your doctor will closely monitor your heart function before and during treatment [3][4].
  2. Trabectedin: Often used as a second-line treatment, this drug helps provide long-term tumor control with a different side effect profile. Doctors will monitor for fatigue and liver enzyme changes [5][6].
  3. Eribulin: A specialized option specifically for patients with advanced liposarcoma who have already received other treatments [7][8].

Note on Side Effects: Chemotherapy can cause fatigue, nausea, and hair loss. Ask your team about palliative care—which is not hospice, but specialized symptom management—to help maintain your quality of life during treatment.

GIST: A Separate Category (Targeted Therapy)

It is crucial to understand that Gastrointestinal Stromal Tumors (GIST) are treated completely differently from other sarcomas. They do not typically respond to traditional chemotherapy. Instead, GIST is treated with Tyrosine Kinase Inhibitors (TKIs)—daily pills that specifically block the “broken” proteins (KIT or PDGFRA) that cause the cancer to grow [9][10].

  • Imatinib: The standard first-line treatment for most GIST patients [9][11].
  • Avapritinib: A breakthrough drug used exclusively for patients with the PDGFRA exon 18 D842V mutation, which does not respond to standard imatinib [12][13].
  • Ripretinib: Used as a later-line treatment when the cancer has developed resistance to other drugs [14][15].

If you have a sarcoma that is NOT GIST, these oral targeted therapies are generally not effective for you.

The Emerging Role of Immunotherapy

Immunotherapy works by “taking the brakes off” your own immune system so it can recognize and attack cancer cells. While it is not a blanket treatment for all sarcomas, it has become a standard-of-care or highly recommended option for very specific subtypes:

  • Alveolar Soft Part Sarcoma (ASPS): This ultra-rare subtype responds exceptionally well to immune checkpoint inhibitors (like atezolizumab or pembrolizumab) [16][17].
  • Undifferentiated Pleomorphic Sarcoma (UPS): Certain cases of UPS show strong responses to immunotherapy, especially if the tumor has specific immune markers in its environment [16][18].

Because treatments for rare subtypes evolve quickly, clinical trials are frequently considered a proactive part of a patient’s care plan. Discussing trials early ensures you have access to the latest precision medicines being developed [2][19].

Common questions in this guide

Is standard chemotherapy used for all types of soft tissue sarcoma?
No, systemic treatments are not one-size-fits-all. While traditional chemotherapy is used for many advanced sarcomas like leiomyosarcoma, it is generally ineffective for gastrointestinal stromal tumors (GIST). Your treatment plan will depend heavily on your specific sarcoma subtype.
How is Gastrointestinal Stromal Tumor (GIST) treated?
GIST is treated with targeted therapies called Tyrosine Kinase Inhibitors (TKIs), rather than traditional chemotherapy. These are daily pills, such as imatinib or avapritinib, that specifically block the abnormal proteins driving the cancer's growth.
What are the risks of using doxorubicin for sarcoma treatment?
Doxorubicin is a common chemotherapy drug that carries a specific risk of cardiotoxicity, meaning it can cause damage to the heart. Your healthcare team will closely monitor your heart function both before and during your treatment to manage this risk.
Is immunotherapy an option for treating soft tissue sarcoma?
Immunotherapy works well for a few specific sarcoma subtypes, though it is not a blanket treatment for all. It is highly recommended for Alveolar Soft Part Sarcoma (ASPS) and certain cases of Undifferentiated Pleomorphic Sarcoma (UPS) that exhibit specific immune markers.
Why should I consider clinical trials for sarcoma treatment?
Because treatments for rare sarcoma subtypes evolve quickly, clinical trials often provide early access to the latest targeted drugs and immunotherapies. Discussing trials early with your oncologist ensures you are aware of all possible precision medicine options.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my specific subtype, how likely is my cancer to respond to traditional chemotherapy like doxorubicin?
  2. 2.For GIST: Has my tumor been tested for the PDGFRA D842V mutation, and does that change my first-line treatment?
  3. 3.What specific side effects (like heart toxicity with doxorubicin) should we be monitoring for?
  4. 4.Are there any open clinical trials for immunotherapy or targeted drugs for my specific subtype?
  5. 5.Why is (or isn't) systemic therapy recommended for my case at this stage?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
  1. 1

    Sarcomas: New Biomarkers and Therapeutic Strategies.

    Nakamura T

    Cancers 2021; (13(20)) doi:10.3390/cancers13205213.

    PMID: 34680364
  2. 2

    Systemic Therapy in Advanced Pleomorphic Liposarcoma: a Comprehensive Review.

    Assi T, Ngo C, Faron M, et al.

    Current treatment options in oncology 2023; (24(11)):1598-1613 doi:10.1007/s11864-023-01139-3.

    PMID: 37843627
  3. 3

    Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma.

    Pautier P, Italiano A, Piperno-Neumann S, et al.

    The New England journal of medicine 2024; (391(9)):789-799 doi:10.1056/NEJMoa2403394.

    PMID: 39231341
  4. 4

    PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma.

    Ryan CW, Merimsky O, Agulnik M, et al.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016; (34(32)):3898-3905 doi:10.1200/JCO.2016.67.6684.

    PMID: 27621408
  5. 5

    Experience with second-line trabectedin in daily clinical practice: case studies.

    Martín-Broto J, Hindi N, Grignani G, et al.

    Future oncology (London, England) 2022; (18(30s)):23-32 doi:10.2217/fon-2022-0519.

    PMID: 36200932
  6. 6

    A Systematic Literature Review of Adverse Events Associated with Systemic Treatments Used in Advanced Soft Tissue Sarcoma.

    Colosia A, Khan S, Hackshaw MD, et al.

    Sarcoma 2016; (2016()):3597609 doi:10.1155/2016/3597609.

    PMID: 27516726
  7. 7

    Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.

    Schöffski P, Chawla S, Maki RG, et al.

    Lancet (London, England) 2016; (387(10028)):1629-37.

    PMID: 26874885
  8. 8

    Efficacy and safety of eribulin mesylate in advanced soft tissue sarcomas.

    Noujaim J, Alam S, Thway K, Jones RL

    Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology 2016; (37(3)):125-30 doi:10.4103/0971-5851.190359.

    PMID: 27688604
  9. 9

    Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors: Current Status and Future Directions.

    Bauer S, Joensuu H

    Drugs 2015; (75(12)):1323-34 doi:10.1007/s40265-015-0440-8.

    PMID: 26187774
  10. 10

    Impact of the KIT/PDGFRA genotype on prognosis in imatinib-naïve Japanese patients with gastrointestinal stromal tumor.

    Cho H, Nishida T, Takahashi T, et al.

    Annals of gastroenterological surgery 2022; (6(2)):241-248 doi:10.1002/ags3.12527.

    PMID: 35261949
  11. 11

    Gastrointestinal Stromal Tumor: Current Approaches and Future Directions in the Treatment of Advanced Disease.

    Cicala CM, Bauer S, Heinrich MC, Serrano C

    Hematology/oncology clinics of North America 2025; (39(4)):773-784 doi:10.1016/j.hoc.2025.04.006.

    PMID: 40368739
  12. 12

    Avapritinib in the treatment of PDGFRA exon 18 mutated gastrointestinal stromal tumors.

    Smrke A, Gennatas S, Huang P, Jones RL

    Future oncology (London, England) 2020; (16(22)):1639-1646 doi:10.2217/fon-2020-0348.

    PMID: 32517495
  13. 13

    Evaluation of the effectiveness and safety of avapritinib in real-world Spanish cases with gastrointestinal stromal tumor and D842V-PDGFRA mutation.

    Nuñez Hernández I, Gómez Palmero C, Delgado JR, et al.

    The oncologist 2025; (30(5)) doi:10.1093/oncolo/oyaf062.

    PMID: 40349140
  14. 14

    Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial.

    Blay JY, Serrano C, Heinrich MC, et al.

    The Lancet. Oncology 2020; (21(7)):923-934 doi:10.1016/S1470-2045(20)30168-6.

    PMID: 32511981
  15. 15

    Ripretinib turns off the switch in GIST.

    Villanueva MT

    Nature reviews. Drug discovery 2019; (18(7)):499 doi:10.1038/d41573-019-00099-4.

    PMID: 31267077
  16. 16

    Immunotherapy for Soft Tissue Sarcomas: Anti-PD1/PDL1 and Beyond.

    Fazel M, Dufresne A, Vanacker H, et al.

    Cancers 2023; (15(6)) doi:10.3390/cancers15061643.

    PMID: 36980528
  17. 17

    B cells are associated with survival and immunotherapy response in sarcoma.

    Petitprez F, de Reyniès A, Keung EZ, et al.

    Nature 2020; (577(7791)):556-560 doi:10.1038/s41586-019-1906-8.

    PMID: 31942077
  18. 18

    Advances in the management of alveolar soft part sarcoma.

    O'Sullivan Coyne G, Naqash AR, Sankaran H, Chen AP

    Current problems in cancer 2021; (45(4)):100775 doi:10.1016/j.currproblcancer.2021.100775.

    PMID: 34284873
  19. 19

    The significance of margins in pediatric Non-Rhabdomyosarcoma soft tissue sarcomas: Consensus on surgical margin definition harmonization from the INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT).

    Sparber-Sauer M, Ferrari A, Spunt SL, et al.

    Cancer medicine 2023; (12(10)):11719-11730 doi:10.1002/cam4.5671.

    PMID: 36744538

This page provides general information on systemic and targeted therapies for soft tissue sarcoma for educational purposes. Always consult your medical oncologist to determine the safest and most effective treatment plan for your specific sarcoma subtype.

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