scholarly journals Real-World Experiences with Pazopanib in Patients with Advanced Soft Tissue and Bone Sarcoma in Northern California

2019 ◽  
Vol 7 (3) ◽  
pp. 48 ◽  
Author(s):  
Tiffany Seto ◽  
Mee-Na Song ◽  
Maily Trieu ◽  
Jeanette Yu ◽  
Manpreet Sidhu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Real World ◽  
Progression Free Survival ◽  
Bone Sarcoma ◽  
Complete Response ◽  
Low Grade ◽  
Northern California ◽  
Histologic Subtypes

Background: Pazopanib was approved for advanced soft tissue sarcoma as a second- or third-line therapy based on the clinical trial “Pazopanib for metastatic soft-tissue sarcoma” (PALETTE). We hypothesized that the real-world experiences may be significantly different from the clinical trial results. Methods: We analyzed the response pattern of patients with advanced soft tissue and bone sarcoma who received pazopanib treatment between 1 January 2011 and 31 October 2018 in Kaiser Permanente Northern California. Results: A total of 123 patients with 23 different histologic subtypes were assessable. One patient with low-grade fibromyxoid sarcoma obtained complete response (CR) after 2 months of treatment with pazopanib, 12 patients (9.7%) obtained partial response (PR), 34 patients (27.6%) had stable disease (SD), while 76 patients (61.8%) developed progressive disease (PD). The disease control rate (DCR) was 46.3% (CR + PR + SD). Among the 12 patients with PR, 3 had undifferentiated pleomorphic sarcoma (UPS), 4 had leiomyosarcoma (LMS), 2 had pleomorphic rhabdomyosarcoma, 1 had pleomorphic liposarcoma, 1 had dedifferentiated liposarcoma, and 1 had angiosarcoma. The median duration of response was 9 months. Two patients with Ewing’s sarcoma had SD for 6 and 13 months, and two patients with osteosarcoma had SD for 6 and 9 months. Among 65 patients assessed at 8 weeks, 9 had a response, and 10 had SD. Among 104 patients assessed at 12 weeks, 12 had a response, and 26 had SD. The median progression-free survival (PFS) was approximately 3 months for all 123 cases and for patients with UPS and LMS. Conclusions: Our cohort of patients with advanced soft tissue and bone sarcoma in Northern California treated with pazopanib had diverse histologic subtypes. The response rate (CR + PR) was higher than that of the PALETTE trial, while the DCR and the median PFS were significantly lower. The observation of PR in two patients with liposarcoma and durable SD in several patients with bone sarcoma indicates that pazopanib has activity in liposarcoma and bone sarcoma.

Olaratumab plus anthracyline in advanced/metastatic soft tissue sarcoma: Data of real-world utilization in Austria.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22550-e22550
Author(s):  
Florian Kocher ◽  
Andreas Seeber ◽  
Lukas Weiss ◽  
Franz Romeder ◽  
Joanna Szkandera ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Real World ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Metastatic Soft Tissue Sarcoma ◽  
Third Line

e22550 Background: Olaratumab is a humanized monoclonal anti platelet-derived growth factor receptor α antibody that has been approved in combination with doxorubicin for the treatment of patients with metastatic soft tissue sarcoma (STS). The purpose of this retrospective study was to assess the clinical efficacy in STS patients treated with olaratumab in a real-world setting in Austria. Methods: Retrospectively collected, longitudinal data from patients treated between November 2016 and September 2018 at 9 Austrian centers were obtained from respective medical charts. Eligible patients were all patients who received at least one dose of olaratumab. Parameters of most interest collected were response rates, progression-free survival (PFS) and overall survival (OS). Results: Altogether 55 patients were included into analysis. Median age was 58 years. In total, 65.5% (n = 36), 21.8% (n = 12) and 12.7% (n = 7) received olaratumab as first-, second- or ≥ third-line treatment, respectively. Olaratumab was administered either in combination with doxorubicin (81.8%, n = 45) or liposomal doxorubicin (16.4%, n = 9); 1 patient received olaratumab as upfront monotherapy. Median PFS and OS were 2.6 and 11.4 months. The objective response rate was 11.4 % and the disease control rate was 40.9 %. Conclusions: In this real-world analysis outcome was less pronounced compared to the results of the Phase Ib/II approval trial ( Tap WD et al. Lancet 2016). Thus, the results of the ongoing phase III trial (NCT02451943) are urgently needed to confirm the efficacy of the combination of olaratumab and doxorubicin in STS patients.

scholarly journals Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma

2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Clinical Data ◽  
Malignant Tumors ◽  
Progression Free Survival ◽  
Average Diameter ◽  
Complete Response ◽  
Target Lesion ◽  
Metastatic Soft Tissue Sarcoma ◽  
Grade 3

Abstract Background: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the evidence and clinical data of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare. Methods: The clinical data of metastatic STS patients who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively analysed. All these patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the effectiveness and safety of nab-paclitaxel and gemcitabine in these patients. Results: A total of 17 patients treated with nab-paclitaxel/ gemcitabine were enrolled in this study. 1 patient with angiosarcoma achieved complete response, 6 patients had partial response, 5 patients achieved stable disease, and 5 patients had progressive disease. The average diameter change in target lesion from baseline was -19.06±45.74%. And median progression free survival was 6 months (95% CI, 2–9 months). Grade 3 / 4 adverse events were not common, included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. Conclusion: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

scholarly journals Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3740
Author(s):  
Nadia Hindi ◽  
Irene Carrasco García ◽  
Alberto Sánchez-Camacho ◽  
Antonio Gutierrez ◽  
Javier Peinado ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Therapeutic Option ◽  
Symptomatic Relief ◽  
Unmet Need ◽  
Real Life ◽  
Progression Free Survival ◽  
Complete Response ◽  
Growth Modulation ◽  
Advanced Soft Tissue Sarcoma

Symptomatic control and tumoral shrinkage is an unmet need in advanced soft-tissue sarcoma (STS) patients beyond first-line. The combination of trabectedin and radiotherapy showed activity in a recently reported clinical trial in this setting. This retrospective series aims to analyze our experience with the same regimen in the real-life setting. We retrospectively reviewed advanced sarcoma patients treated with trabectedin concomitantly with radiotherapy with palliative intent. Growth-modulation index (GMI) was calculated as a surrogate of efficacy. Forty metastatic patients were analyzed. According to RECIST, there was one (2.5%) complete response, 12 (30%) partial responses, 18 (45%) disease stabilizations, and nine (22.5%) progressions. After a median follow-up of 15 months (range 2–38), median progression-free survival (PFS) and overall survival (OS) were 7.5 months (95% CI 2.8–12.2) and 23.5 months (95% CI 1.1–45.8), respectively. Median GMI was 1.42 (range 0.19–23.76), and in 16 (53%) patients, it was >1.33. In patients with GMI >1.33, median OS was significantly longer than in those with GMI 0–1.33 (median OS 52.1 months (95% CI not reached) vs. 8.9 months (95% CI 6.3–11.6), p = 0.028). The combination of trabectedin plus radiotherapy is an active therapeutic option in patients with advanced STS, especially when tumor shrinkage for symptomatic relief is needed.

scholarly journals Real-World Outcomes of Advanced Soft Tissue Sarcoma Patients Treated with Pazopanib

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Fawaz A ◽  
◽  
Shim I ◽  
Tilley D ◽  
Kelaney MR ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Real World ◽  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Advanced Soft Tissue Sarcoma ◽  
Clinical Trial Setting ◽  
Trial Setting

Background: Pazopanib is an oral multitarget tyrosine kinase inhibitor that is currently approved for the treatment of select subtypes of advanced Soft Tissue Sarcoma (STS) in patients who have progressed on prior anthracyclinebased chemotherapy regimens. In this study, we examine data from multiple centers to assess the efficacy of pazopanib in practice outside of a clinical trial setting. Methods: A retrospective chart analysis was conducted for pre-treated, advanced soft tissue sarcoma patients who began treatment with pazopanib in Alberta, Canada and Cairo, Egypt (2012-2018). Results: In total, 39 predominantly male (56.4%) patients received pazopanib. The median age was 51, 67% of whom had an ECOG of one or less. The predominant sarcoma subtype was leiomyosarcoma (30.8%), and all patients had received at least one prior line of systemic therapy. Thirtytwo of the 39 patients (82%) were initially given the full dose of 800mg with a median time on treatment of 116 days. Seven of the 39 (18%) patients required a dose reduction while on treatment. A majority (94.9%) of patients ultimately discontinued pazopanib treatment for reasons including death (21.6%), disease progression (62.2%), and toxicity (16.4%). The median progression-free and overall survival for these patients was 4.1 months (95%CI, 3.6-4.5) and 8.4 months (95% CI, 4.3-12.5), respectively. Conclusion: Pazopanib is an efficient and generally well-tolerated oral systemic therapy for the treatment of advanced, pre-treated, non-adipocytic soft tissue sarcoma. These results show the efficacy of pazoponib outside of a clinical trial setting.

Phase II trial of pegylated arginine deiminase in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11508-11508
Author(s):  
Brian Andrew Van Tine ◽  
Angela C. Hirbe ◽  
Jingqin Luo ◽  
Peter John Oppelt ◽  
Mia C. Weiss ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Progression Free Survival ◽  
Data Safety Monitoring Board ◽  
Arginine Deiminase ◽  
Phase 2 ◽  
Cycle Enzyme ◽  
Dose Reductions

11508 Background: Soft tissue sarcoma (STS) is dependent on extracellular arginine as it often lacks expression of argininosuccinate synthase 1 (ASS1), the urea cycle enzyme needed to produce intracellular arginine. PEGylated arginine deiminase (ADI-PEG 20) is an extracellular arginine-degrading enzyme that causes ASS1 deficient tumors to enter the starvation state. Preclinical data demonstrated that addition of docetaxel (D) with ADI-PEG20 upregulates expression of the transporter for gemcitabine (G), overcoming transporter level resistance, and causing increased cell death. In vivo modeling demonstrated that the combination of ADI-PEG20 with G+D was superior to G+D alone. Therefore, we performed a phase 2 trial testing the addition of ADI-PEG20 to G+D. Methods: We performed an investigator-initiated, phase 2, multicenter, multi-arm clinical trial of ADI-PEG20 with G (90minute infusion)+D in STS, Ewing’s, osteosarcoma and small cell lung cancer. We are reporting Arm A, the STS arm. Eligible patients had STS that would be standardly treated with G+D that had progressed on at least one prior line of therapy with measurable disease by RECIST1.1 and had adequate organ function Based on a historic median PFS of 6.2 months for G+D, we targeted to enroll N = 75 patients in cohort A to detect a 2.8 month improvement with 80% power at a 5% alpha level. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), clinical benefit rate (CBR), safety, tolerability, cancer related mortality, and correlation with ASS1 expression by IHC. We evaluated PFS by Kaplan-Meier method and estimated overall response rate (ORR). Results: 75 patients were treated and deemed evaluable. The trial underwent two dose reductions by the data safety monitoring board due to prolonged neutropenia and thrombocytopenia preventing the use of day 8 G+D, consistent with preclinical mechanism of action data showing that ADI-PEG 20+D enhanced G uptake. Originally, the G dose was 900mg/m2 reduced first to 750mg/m2 then to 600mg/m2. D was dose reduced at the time of the second dose reduction from 75mg/m2 to 60mg/m2. ADI-PEG20 was given at a fixed intramuscular dose (36 mg/m2) weekly. The need for two dose reductions affected the PFS. The PFS/OS (months) were for the 600mg/m2 group (n = 31) was 6.0/N.D., leiomyosarcoma (LMS) (N = 33) 7.2/22.5, liposarcoma 5.1/17.4, and other (N = 36) 2.8/15.0. Responses were 8% complete (6/75) (3 LMS, 1 synovial and 2 angiosarcoma), 17% partial (13/75), and 43% stable disease (32/75), for an ORR of 25% (19/75) and CBR of 68% (51/75). There was a trend for ASS1 negative tumors to benefit more than ASS1 positive tumors. Conclusions: The combination of ADI-PEG20 with G+D can be safely and effectively given at a dose of 600mg/m2 G and 60mg/m2 D. Future randomized trials of ADI-PEG20 with G+D are planned. Clinical trial information: NCT03449901.

scholarly journals Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

scholarly journals Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

Sarcoma ◽  
1998 ◽  
Vol 2 (3-4) ◽  
pp. 171-177
Author(s):  
S. Murray Yule ◽  
Roderick Skinner ◽  
Martin W. English ◽  
Mike Cole ◽  
Andrew D. J. Pearson ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Primary Tumour ◽  
Treatment Protocol ◽  
Disease Free Survival ◽  
Local Therapy ◽  
Complete Response ◽  
One Year ◽  
Sarcoma Treatment

Background.Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.Patients and Methods.Twenty-one children with STS (16 rhabdomyosarcoma) who presented with unresectable tumours were treated with five courses of ifosfamide (9 g/m2) and etoposide (600 mg/m2). Patients who did not achieve a complete response then received local therapy. Chemotherapy with ifosfamide combined with etoposide, vincristine (1.5 mg/m2and doxorubicin (60 mg/m2) or vincristine and actinomycin D (1.5 mg/m2) was continued for one year.Results and Discussion.Objective responses to five courses of ifosfamide and etoposide were seen in all patients. Disease free survival (DFS) at a median follow up of 59 months was 57% (95% CI 29–75%). The DFS of children who received local therapy was 89% compared with 33% in those who received chemotherapy alone (p=0.027). Locoregional recurrences did not occur in children who received radiotherapy to the site of the primary tumour. Ifosfamide-based chemotherapy does not reduce the incidence of loco-regional recurrence in children who do not receive local therapy.

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