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

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.

Download Full-text

The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: A retrospective cross-sectional study of a Turkish cohort

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220904138 ◽

2020 ◽

Vol 26 (7) ◽

pp. 1657-1666

Author(s):

Mustafa Karaağaç ◽

Yasin Sezgin ◽

Melek Karakurt Eryılmaz ◽

Murat Araz ◽

Muhammet Ali Kaplan ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Performance Status ◽

Soft Tissue Sarcomas ◽

Progression Free Survival ◽

First Line ◽

Advanced Soft Tissue Sarcoma ◽

Free Survival ◽

Common Grade

Introduction Soft tissue sarcomas are a heterogeneous and rare group of cancers with a short median overall survival despite the chemotherapy. Pazopanib has approval for the treatment of advanced soft tissue sarcoma. We aimed to investigate the clinical outcomes of Turkish patients with advanced soft tissue sarcoma who received pazopanib. Patients and methods This was a retrospective study. The inclusion criteria were: ≥18 years of age, having histologically proven advanced soft tissue sarcoma and receiving pazopanib at least one day. Results A total of 79 patients were assessed in this study. The median age was 49.6 years. The average dose intensity of pazopanib was 767 mg (400–800). The median duration of pazopanib treatment was 6.11 months. Fourteen patients (17.7%) used pazopanib at first line for advanced soft tissue sarcomas. The most common cause of discontinuation of pazopanib was the progression of the disease (89.6%). Pazopanib was well tolerated. The most common grade ≥3 side effect was anemia. The most common grade ≤2 side effects were anemia and hyperbilirubinemia. The median progression-free survival, overall survival, and follow-up were 3.97 months, 11.40 months, and 32.72 months, respectively. Female gender, good performance status, and the presence of pazopanib-induced hypothyroidism were associated with longer progression-free survival. Also, good performance status and being a responder to first-line treatment were associated with longer overall survival. Conclusions We showed that pazopanib was well tolerated and had clinical benefit in patients with advanced soft tissue sarcoma in a Turkish cohort. This is the first study that suggests pazopanib-induced hypothyroidism may act as a predictive marker for better outcomes in patients with advanced soft tissue sarcoma.

Download Full-text

Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial

Journal of Clinical Oncology ◽

10.1200/jco.21.00124 ◽

2021 ◽

pp. JCO.21.00124

Author(s):

Anne-Sophie Defachelles ◽

Emilie Bogart ◽

Michela Casanova ◽

Johannes H. M. Merks ◽

Gianni Bisogno ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Adverse Events ◽

Objective Response Rate ◽

Response Rate ◽

Phase Ii Trial ◽

Objective Response ◽

Progression Free Survival ◽

Free Survival

PURPOSE The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS). METHODS In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2 once a day on day 1 and day 8) and irinotecan (50 mg/m2 once a day from day 1 to day 5) with and without temozolomide (125 mg/m2 once a day from day 1 to day 5 and 150 mg/m2 once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445 ). RESULTS Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025). CONCLUSION The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.

Download Full-text

Survival of soft tissue sarcoma patients after completing six cycles of first-line anthracycline containing treatment: an EORTC-STBSG database study

Clinical Sarcoma Research ◽

10.1186/s13569-020-00137-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Arie Jan Verschoor ◽

Saskia Litière ◽

Sandrine Marréaud ◽

Ian Judson ◽

Maud Toulmonde ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Confidence Interval ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

Median Progression Free Survival ◽

First Line Treatment

Abstract Background Doxorubicin based chemotherapy is standard first line treatment for patients with soft tissue sarcoma. Currently several options to improve survival after doxorubicin based chemotherapy are being studied. This study reports on survival after completing 6 cycles of doxorubicin containing first line treatment, which is important when designing studies trying to improve outcomes of first line treatment. Methods A retrospective database analysis was performed on 2045 patients from 12 EORTC sarcoma trials (inclusion period 1980–2012) receiving first line doxorubicin based chemotherapy for advanced soft tissue sarcoma in order to establish progression free survival and overall survival after completing 6 cycles of first line doxorubicin based chemotherapy. Endpoints were overall survival and progression free survival. Factors studied were histologic subtype and type of doxorubicin chemotherapy. Results 748 of 2045 (36.6%) received at least 6 cycles and did not progress during or at the end of chemotherapy. 475 of 2045 (23.2%) of patients received exactly 6 cycles and did not progress during or at the end of chemotherapy. Median progression free survival after 6 cycles of doxorubicin based chemotherapy was 4.2 months (95% confidence interval 3.7–4.8) and median overall survival 15.7 months (14.0–17.8). Median progression free survival and overall survival from randomisation/registration were 8.7 months (95% confidence interval 8.2–9.1) and 20.1 months (95% confidence interval 18.3–22.3) respectively. Significant differences in progression free survival were found between chemotherapy regimens, but not for overall survival. These data are also reported for patients receiving 7 or more cycles of chemotherapy and for patients with 3 or more cycles of chemotherapy. Conclusion This large retrospective study is the first to report progression free survival and overall survival after completion of 6 cycles of first line doxorubicin containing chemotherapy. These results are important when designing new studies exploring for example maintenance therapy after doxorubicin based chemotherapy.

Download Full-text

Efficacy and safety of anlotinib plus TQB2450 in patients with advanced soft tissue sarcoma: A multicenter, single armed, phase 1b trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11547 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11547-11547

Author(s):

Jiayong Liu ◽

Zhengfu Fan ◽

Wei Guo ◽

Tian Gao ◽

Shu Li ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Kinase Inhibitor ◽

Soft Part ◽

Epithelioid Sarcoma ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Phase 1B ◽

Anthracycline Chemotherapy

11547 Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, had been prove to be effective for the treatment of advanced or metastatic soft tissue sarcoma(STS) faild anthracycline chemotherapy. With the lack of prospective data of combination of PDL-1 inhibitor and antiangiogenic agent, we designed a phase 1b study to investigated the efficacy and safety of anlotinib plus TQB2450 in patients with STS. Methods: Eligible patients (age 18-70, ECOG 0-1, with histopathologically confirmed advanced STS, at least one measurable lesion according to RECIST 1.1, and previously received front-line anthracycline chemotherapy) were included and received anlotinib (12mg qd, D1-14, 21d/cycle) plus TQB2450 (1200 mg, IV, D1, 21d/cycle) until disease progression or intolerable toxicities.The primary endpoint was objective response rate (ORR), secondary endpoints included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR). Results: From January 2019 to January 2021, 30 pts were enrolled1, 12 alveolar soft part sarcoma and 18 others (7 synovial sarcoma, 4 leiomyosarcoma, 5 undifferentiated pleomorphic sarcoma, 1 fibrosarcoma and 1 epithelioid sarcoma). ORR by RECIST was 36.7%, DCR was 83.3%, 11/30 pts had PR, 14/30 (46.7%) had SD, 5/30 (16.7%) PD. Median PFS was 9.6 m in all pts and 4.9m. in non-ASPS, respectively. Median OS in non-ASPS was 10.27m, while mOS in all pts and both mPFS and mOS in ASPS had not been reached. Notably, to ASPS pts, ORR was 75%, and DCR was 100%. The most common 1-2 grade treatment-related adverse reaction (TRAE) was hypothyroidism (19/30,63.3%)，hypercholesterolemia (16/30, 53.3%) and hypertriglyceridemia (16/30, 53.3%), the most common ≥3 grade TRAEs were hypertriglyceridemia (3/30, 10%). 6 SAE (20%) occurred, including 2 pneumothorax, 1 Immune associated hapatic injury, 1 hypotension, 1 Immune myocarditis and 1 diabetic ketoacidosis. Conclusions: The combination of anlotinib and TQB2450 showed promising activity in second-line treatment of advanced STS, especially in ASPS, with well tolerance and acceptable toxicity.

Download Full-text

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219891631 ◽

2019 ◽

Vol 26 (6) ◽

pp. 1331-1342

Author(s):

Irena Ilic ◽

Sandra Sipetic ◽

Jovan Grujicic ◽

Milena Ilic

Keyword(s):

Overall Survival ◽

Objective Response Rate ◽

Advanced Nsclc ◽

Response Rate ◽

Meta Analysis ◽

Objective Response ◽

Stage Iv ◽

Progression Free Survival ◽

First Line ◽

Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Download Full-text

Tumor metabolic volume by 18F-FDG-PET as a prognostic predictor of first-line pembrolizumab for NSCLC patients with PD-L1 ≥ 50%

Scientific Reports ◽

10.1038/s41598-020-71735-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ou Yamaguchi ◽

Kyoichi Kaira ◽

Kosuke Hashimoto ◽

Atsuto Mouri ◽

Ayako Shiono ◽

...

Keyword(s):

Objective Response ◽

Prognostic Significance ◽

Standardized Uptake Value ◽

Progression Free Survival ◽

Predictive Marker ◽

Distant Metastases ◽

Metabolic Tumor Volume ◽

First Line ◽

Prognostic Predictor ◽

Fdg Uptake

Abstract There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression ≥ 50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-d-glucose (18F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels ≥ 50% who underwent 18F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUVmax) on 18F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression ≥ 75%. Metabolic tumor activity assessed as MTV from 18F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression ≥ 50%, especially for adenocarcinoma.

Download Full-text

Tumor genomic analysis for 128 renal cell carcinoma (RCC) patients receiving first-line everolimus: Correlation between outcome and mutations status in MTOR, TSC1, and TSC2.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.484 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 484-484 ◽

Cited By ~ 4

Author(s):

Martin Henner Voss ◽

David Chen ◽

Mahtab Marker ◽

Jianing Xu ◽

Parul Patel ◽

...

Keyword(s):

Somatic Mutations ◽

Objective Response ◽

Case Series ◽

Genomic Analysis ◽

Progression Free Survival ◽

Mtor Inhibitors ◽

Sequence Coverage ◽

First Line ◽

Mutation Status ◽

Functional Investigation

484 Background: MTOR inhibitors are standard agents in the management of advanced RCC. Case series have suggested somatic mutations in MTOR, TSC1, and TSC2 may sensitize tumors to everolimus (EVE) [Voss et al., CCR 2014; Kwiatkowski et al., CCR 2016]. We sought to test this hypothesis through next generation sequencing (NGS) of tumors from a large cohort of patients (pts) treated with everolimus (EVE) on the randomized RECORD3 trial of first-line EVE vs. sunitinib. Methods: Somatic mutations were investigated using a custom exon-targeted NGS platform with deep sequence coverage. This analysis focused on mutations in TSC1, TSC2, PTEN, PIK3CA, and MTOR. Association between genotypes and progression free survival (PFS) was assessed by Cox PH models and log-rank tests. Mutations in other pathways and non-genetic covariates were investigated. Functional investigation of individual mutations in MTOR, TSC1, and TSC2 were undertaken. Results: 238 pts received 1st line EVE with median PFS of 7.85 mo (95% CI 5.6-8.2). Tumor sampleswere analyzed for 128 pts. Median depth of coverage was ~540X. There was no correlation between PFS and mutation status of mTOR, TSC1, or TSC2 (15 pts [12%]; HR 0.99 [95% CI 0.47-2.07]; p=0.4697); the objective response rate (ORR) in this group was 0%. Individual PFS for all 15 pts clustered outside the 95% CI for the population of 128 everolimus-treated pts (8 pts PFS<2.8mo; 7pts PFS>8.3mo). 3 of 8 pts with PFS<2.8mo had >1 mutation in MTOR, TSC1, or TSC2, while none among the 7 pts with PFS >8.3mo. When including pts with mutations in PTEN, PIK3Ca, MTOR, or TSC1 (30pts [23%]), we found no association between mutation status and PFS (HR 1.02 [95% CI 0.61-1.71]; p=0.3025). Functional investigations suggest varying biologic effects of individual mutations. Conclusions: "One-dimensional" mutation status for core components of the MTOR signaling pathway did not correlate with PFS in this dataset. Grouping based on more detailed characterization incorporating copy number status and functional annotation may provide better insights and should be considered for future biomarker development. Clinical trial information: NCT00903175.

Download Full-text

A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib (REG) in patients (pts) with nonadipocytic soft tissue sarcoma (STS) previously treated with pazopanib (PAZ).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11021 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11021-11021

Author(s):

Nicolas Penel ◽

Jean-Yves Blay ◽

Jennifer Wallet ◽

Isabelle Laure Ray-Coquard ◽

Axel Le Cesne ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Performance Status ◽

Objective Response ◽

Dose Intensity ◽

Progression Free Survival ◽

Final Analysis ◽

Double Blind ◽

Phase 2 Trial ◽

Previously Treated

11021 Background: After we demonstrated the activity of REG in pts with advanced non-adipocytic STS (MirTLO 2016), we conducted a dedicated study in pts previously treated with PAZ+chemo. Methods: We report here the 5th cohort of a double-blind randomized phase 2 trial (NCT01900743). Pts were treated with regorafenib (160mg/d, 21/28d) or placebo (PB). Pts receiving placebo were offered optional cross-over in case of centrally confirmed disease progression. The primary endpoint was centrally-reviewed RECIST-based progression-free survival (PFS), evaluated on the intent-to-treat dataset. A total of 24 events was required to ensure a 90%-power for HR = 0.33 (median PFS, 3·6 vs 1·2 months), with a 1-sided α = 0·1. Overall survival (OS) was a secondary endpoint. Results: From 12/2015 to 10/2017, 37 pts were randomized (18 REG vs 19 PB) and included in the final analysis. The median age was 60 (36-76). There were 28 women (76%). All pts had a performance status 0 or 1. Histological subtypes included 24 leiomyosarcoma (11 vs 13, in REG and PB, respectively), 1 synovial sarcoma (REG), 12 other sarcoma (7 vs 5). All pts had previously been treated with PAZ +chemo (including doxorubicin: 19 vs 17; ifosfamide: 11 vs 3; trabectedin: 11 vs 9; and dacarbazine: 7 vs 6), with 2-6 prior lines. The median relative dose intensity of REG was 0·86, range 0·41-1. Out of 19 pts assigned to placebo, 13 switched to REG after progression. There was no reported objective response. We observed a significant benefit of REG compared to PB in terms of PFS (HR = 0·38; 95%CI, 0·19-0·76; p = 0·007; median PFS = 2·1 vs 1·1 months, respectively), and OS despite the cross-over (HR = 0·41; 95%CI, 0·17-0·98; p = 0·04; median OS = 18·6 vs 8·2 months). Before cross-over, the most common clinically significant grade 3 or higher adverse events were diarrhea (4 vs 0), dyspnea (3 vs 1), arterial hypertension (2 vs 0), hand-foot skin reaction (2 vs 0). Conclusions: The present study demonstrates that regorafenib has a clinically meaningful anti-tumor activity in pts with non-adipocytic soft tissue sarcoma pretreated by both chemotherapy and pazopanib, improving PFS and OS. Clinical trial information: NCT01900743.

Download Full-text

Cancer immunotherapy using trabectedin and nivolumab in advanced soft tissue sarcoma: A retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.40 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 40-40 ◽

Cited By ~ 2

Author(s):

Erlinda Maria Gordon ◽

Kamalesh Kumar Sankhala ◽

Nathan Stumpf ◽

Joshua Ravicz ◽

Suzan Arasheben ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Retrospective Analysis ◽

Progression Free Survival ◽

Myxoid Liposarcoma ◽

Synergistic Activity ◽

Advanced Soft Tissue Sarcoma ◽

Efficacy Analysis ◽

Pleomorphic Sarcoma ◽

Grade 3

40 Background: To restore innate tumor surveillance that is lost in cancer patients, a tumoricidal agent may have synergistic activity with an immune checkpoint inhibitor. Herein, we report on a retrospective analysis of our clinical experience using trabectedin, an alkylating agent, and nivolumab, a PD-1 inhibitor in advanced soft tissue sarcoma. Methods: Twenty previously treated STS patients received trabectedin (1.5 mg/m2 continuous intravenous infusion, CIV, for 24 hours) every 3 weeks, and nivolumab (3 mg/kg IV over 30 minutes) every 2 weeks. Safety/toxicity was analyzed using the NIH/NCI CTCAE v.4.03. Tumor responses were assessed by RECIST v1.1 and immune-related response criteria (irRECIST). Results: Histologic subtypes in 20 patients include undifferentiated pleomorphic sarcoma (UPS; n = 7), leiomyosarcoma (n = 5), synovial sarcoma (n = 2), myxoid liposarcoma (n = 4) and chondrosarcoma (n = 2). All patients had metastatic disease and a median of 4 lines of prior chemotherapy. Safety analysis (n = 20): Grade 3 treatment emergent adverse events include anemia (n = 2), fatigue (n = 1), decreased platelet count (n = 1), decreased granulocyte count (n = 1) and increased creatine kinase (n = 1). Efficacy analysis (n = 17): Seventeen patients were followed for at least 6 months and their results are reported here. There were 4 partial responses (UPS = 1, myxoid liposarcoma = 1, chondrosarcoma = 1, leiomyosarcoma = 1), 7 stable disease, and 6 progressive disease, with best overall response rate of 23.5%, median progression free survival (PFS) of > 11.6 months (range: 2.3- > 16.9 months), median overall survival (OS) of > 14.2 months (4.5- > 24.0 months), 6 month PFS rate of 64.7%, and 6 month OS rate of 94.1%. In a Phase 3 study, the median PFS was 4.2 months using trabectedin alone (Demetri et al., 2015). Conclusions: Taken together, the data suggest that paired administration of trabectedin and nivolumab is safe, and that this chemo-/immuno-therapy approach has synergistic activity.

Download Full-text

Update on Systemic Therapy for Advanced Soft-Tissue Sarcoma

Current Oncology ◽

10.3747/co.27.5475 ◽

2020 ◽

Vol 27 (11) ◽

pp. 25-33 ◽

Cited By ~ 5

Author(s):

A. Smrke ◽

Y. Wang ◽

C. Simmons

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Systemic Therapy ◽

English Language ◽

Standard Of Care ◽

Current Evidence ◽

First Line ◽

First Line Therapy

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.

Download Full-text