What are the treatment options for Sarcoma (malignant tumor of connective tissue)?

From the Guidelines

Sarcoma treatment should prioritize a multidisciplinary approach, with standard first-line treatment being single-agent doxorubicin, as it offers the best balance of efficacy and tolerability, according to the most recent guidelines 1. The treatment of sarcoma, a malignant tumor of connective tissue, involves a combination of surgery, radiation therapy, and chemotherapy.

• The primary goal is to achieve complete surgical removal of the tumor with wide margins, which is often feasible for localized disease.
• For advanced soft tissue sarcomas (STS), systemic treatments are not curative, with a median survival time of 12-18 months, and treatment recommendations should be guided by patient performance status, disease extent, rate of progression, and potential sensitivity to treatment 1.
• Chemotherapy options include:
  • Single-agent doxorubicin as the standard first-line treatment (I,A) 1.
  • Ifosfamide as an alternative first-line option if anthracyclines are contraindicated, and as a standard second-line therapy (I,B) 1.
  • Combination therapy with doxorubicin and ifosfamide, which may be considered in individual patients where a response would improve symptoms or facilitate other treatment modalities (II,B) 1.
  • Additional second-line agents, such as trabectedin, and the combination of gemcitabine/docetaxel or gemcitabine/dacarbazine, with the choice of agent depending on histology, toxicity profile, and patient preference (II,B) 1.
• For specific sarcoma subtypes, targeted therapies, such as NTRK inhibitors for tumors harboring NTRK-fusions, and immunotherapy in subtypes like alveolar soft part sarcoma (ASPS), should be considered first-line if a suitable drug is available (III,A) 1.
• Surgical resection of locally recurrent disease should be considered where feasible, and for patients with oligometastatic disease, surgery, radiotherapy, or ablative therapies should be considered in individual cases, although there are limited data on survival benefit (III,B) 1.

From the FDA Drug Label

The efficacy of pazopanib was evaluated in VEG110727, a randomized, double-blind, placebo-controlled, multicenter trial ( NCT00753688). Patients with metastatic STS who had received prior chemotherapy, including anthracycline treatment, or were unsuited for such therapy, were randomized (2:1) to receive pazopanib 800 mg once daily or placebo The major efficacy outcome measure was PFS assessed by independent radiological review Additional outcome measures were OS, ORR, and duration of response. Efficacy results are presented in Table 9 and Figure 2.

The treatment option for Sarcoma (malignant tumor of connective tissue) is pazopanib 800 mg once daily.

• Key points:
  • Pazopanib is used for patients with metastatic STS who have received prior chemotherapy or are unsuited for such therapy.
  • The major efficacy outcome measure is PFS assessed by independent radiological review.
  • Additional outcome measures include OS, ORR, and duration of response. 2

From the Research

Treatment Options for Sarcoma

The treatment options for sarcoma, a malignant tumor of connective tissue, vary depending on the stage and type of the disease.

• Surgery is the standard treatment for localized soft tissue sarcoma, with radiation therapy used in selected cases 3.
• For recurrent, unresectable, or metastatic disease, systemic chemotherapy is the standard treatment, with options including doxorubicin, ifosfamide, gemcitabine, docetaxel, and pazopanib 4, 3, 5, 6.
• Adjuvant chemotherapy may be used for high-risk localized soft tissue sarcoma, although its effectiveness in elderly patients is unclear 3, 5.
• Neoadjuvant radiochemotherapy can be effective in achieving local functional tumor control in advanced and recurrent soft tissue sarcoma, with a regimen of accelerated split-course radiation and concurrent chemotherapy using adriamycin and ifosfamide showing promising results 7.
• Targeted therapies, such as pazopanib, eribulin, and trabectedin, have been approved for specific sarcoma subtypes and can be used as second-line or further line treatments 3, 5, 6.

Chemotherapy Options

Chemotherapy options for sarcoma include:

• Doxorubicin and ifosfamide, which remain the most effective chemotherapy drugs available for the treatment of majority of these tumors 6.
• Gemcitabine and docetaxel, which can be used as a second-line treatment 3, 6.
• Pazopanib, which is approved for all nonadipocytic sarcomas 6.
• Eribulin, which is approved for patients with adipocytic sarcomas 6.
• Trabectedin, which is approved for patients with leiomyosarcoma and liposarcoma 6.

Considerations for Elderly Patients

For elderly patients with sarcoma, the treatment approach may need to be adjusted due to age-related factors.

• Surgery is still the standard therapy for localized bone and soft tissue sarcomas, even in elderly patients 5.
• Adjuvant chemotherapy may not be recommended for elderly patients with osteosarcoma due to lack of evidence on its effectiveness 5.
• Doxorubicin monotherapy is considered the standard regimen for first-line treatment of advanced soft tissue sarcoma in elderly patients, with pazopanib as an alternative option 5.