MEK Inhibitor and a PDL1 Inhibitor Patients With Locally Advanced and/or Metastatic Soft Tissue Sarcoma

Purpose.To make recommendations for the use of doxorubicin-based chemotherapy in patients with soft-tissue sarcoma.Patients.The recommendations apply to patients with symptomatic unresectable locally advanced or metastatic soft-tissue sarcoma who are candidates for palliative chemotherapy.Methods.A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline.Results.Eight randomized trials comparing doxorubicin-based combination versus doxorubicin single-agent chemotherapy were reviewed. Response rates and overall survival were evaluated using pooled statistical analysis.The pooled response data in 2281 patients showed a slight trend favouring the combination therapy, although this did not reach statistical significance (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.60–1.05;p=0.10). Survival data could only be abstracted from six studies involving 2097 patients, and showed no significant advantage for combination therapy (OR, 0.84; 95% CI, 0.67–1.06;p=0.13). Data on adverse effects could not be combined in a meta-analysis; however nausea, vomiting and myelosuppression were consistently more severe with combination chemotherapy than with single-agent chemotherapy.Discussion.Single-agent doxorubicin is an appropriate first-line chemotherapy option for advanced or metastatic soft-tissue sarcoma. Some doxorubicin-based combination chemotherapy regimens, given in conventional doses, produce only marginal increases in response rates, at the expense of increased adverse effects, and with no improvements in overall survival. Future randomized clinical trials should compare new regimens, whose activity has been established in single-arm studies, with single-agent doxorubicin, and include quality of life as an outcome measure.

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Impact of chemotherapy on survival in locally advanced and metastatic soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e23536 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e23536-e23536

Author(s):

Mark Ashamalla ◽

Theodore Yanagihara ◽

Adel Guirguis ◽

Hani Ashamalla

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Locally Advanced ◽

Metastatic Soft Tissue Sarcoma

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A Phase II Study of Docetaxel in Chemotherapy-Naïve Patients With Recurrent or Metastatic Adult Soft Tissue Sarcoma

Sarcoma ◽

10.1080/13577149878136 ◽

1998 ◽

Vol 2 (1) ◽

pp. 29-33 ◽

Cited By ~ 8

Author(s):

Vivien Bramwell ◽

Martin Blackstein ◽

Karl Belanger ◽

Shail Verma ◽

Sandra Beare ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Performance Status ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Haematological Toxicity ◽

Dose Intensity ◽

Ecog Performance Status ◽

Metastatic Soft Tissue Sarcoma ◽

Toxicity Criteria

Purpose:To determine the efficacy and toxicity of docetaxel as first-line chemotherapy in adult patients with locally advanced and/or metastatic soft tissue sarcoma (STS).Patients/methods.Thirty eligible patients, with histologically proven STS, Eastern Cooperative Oncology Group (ECOG) performance status 0–2 and bidimensionally measurable disease, entered this study. None had received previous chemotherapy. Docetaxel 100 mgm−2was given as a 1-h intravenous infusion every 3 weeks. Patients were evaluable for response, evaluated by WHO criteria, after one cycle of chemotherapy and toxicity was graded by NCIC-CTG common toxicity criteria.Results.One hundred and thirty two cycles were aldministered, with a range per patient of 1–9. The median delivered dose intensity was 32.2 mgm−2 week−1(planned 33.3 mgm−2 week−1) and 67% of patients received ≥90% planned dose intensity. There were three partial responses (10.7%; 95% confidence interval 2.3–28.2) with a median duration of 7 months (range 6.4–8.3 months). Thirty patients were evaluable for non-haematological toxicity and 28 for haematological toxicity (repeat counts were not available in two patients). Haematological toxicity was moderately severe, with 18 (64%) patients experiencing at least one episode of grade 4 neutropenia, and 7 (25%) patients experiencing febrile neutropenia.Conclusions.In this study, activity of docetaxel in adult chemotherapy-naïve patients with advanced STS was modest

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A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23531 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23531-e23531

Author(s):

Xin Huang ◽

Zhaoming Ye ◽

Tao Li ◽

Yongzhong Wei ◽

Shoufeng Wang ◽

...

Keyword(s):

Clinical Trial ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Disease Control ◽

Interim Analysis ◽

Locally Advanced ◽

Line Treatment ◽

First Line ◽

Metastatic Soft Tissue Sarcoma ◽

First Line Treatment

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.

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