Efficacy and safety of trabectedin as an early treatment for advanced or metastatic liposarcoma and leiomyosarcoma.

AIMS: We aimed to evaluate the effect of prior chemotherapies on the outcomes of patients with liposarcoma and leiomyosarcoma treated with trabectedin as a 24-h infusion every 3 weeks. PATIENTS & METHODS: Data from 129 patients who received trabectedin as second-line treatment following failure with an anthracycline/ifosfamide and those who had received at least two lines of prior chemotherapy were analyzed. RESULTS: Forty seven patients received one prior regimen (group A) and 82 patients received at least two lines of chemotherapy (group B). A favorable trend in median time to progression (4.4 vs 3.0 months), progression-free survival (4.4 vs 2.6 months) and overall survival (17.4 vs 13.3 months) was found in group A. A trend toward higher overall response rate (6.4 vs 4.9%) and disease control rate (34.0 vs 26.8%) also favored group A. Both groups had equivalent safety profiles. CONCLUSION: All efficacy outcomes were better in patients who received trabectedin as second-line treatment compared with patients with more extensive prior therapy.

Quality of Surgery and Outcome in Localized Gastrointestinal Stromal Tumors Treated Within an International Intergroup Randomized Clinical Trial of Adjuvant Imatinib.

Importance: The association between quality of surgery and overall survival in patients affected by localized gastrointestinal stromal tumors (GIST) is not completely understood. Objective: To assess the risk of death with and without imatinib according to microscopic margins status (R0/R1) using data from a randomized study on adjuvant imatinib. Design, Setting, and Participants: This is a post hoc observational study on patients included in the randomized, open-label, phase III trial, performed between December 2004 and October 2008. Median follow-up was 9.1 years (IQR, 8-10 years). The study was performed at 112 hospitals in 12 countries. Inclusion criteria were diagnosis of primary GIST, with intermediate or high risk of relapse; no evidence of residual disease after surgery; older than 18 years; and no prior malignancies or concurrent severe/uncontrolled medical conditions. Data were analyzed between July 17, 2017, and March 1, 2020. Interventions: Patients were randomized after surgery to either receive imatinib (400 mg/d) for 2 years or no adjuvant treatment. Randomization was stratified by center, risk category (high vs intermediate), tumor site (gastric vs other), and quality of surgery (R0 vs R1). Tumor rupture was included in the R1 category but also analyzed separately. Main Outcomes and Measures: Primary end point of this substudy was overall survival (OS), estimated using Kaplan-Meier method and compared between R0/R1 using Cox models adjusted for treatment and stratification factors. Results: A total of 908 patients were included; 51.4% were men (465) and 48.6% were women (440), and the median age was 59 years (range, 18-89 years). One hundred sixty-two (17.8%) had an R1 resection, and 97 of 162 (59.9%) had tumor rupture. There was a significant difference in OS for patients undergoing an R1 vs R0 resection, overall (hazard ratio [HR], 2.05; 95% CI, 1.45-2.89) and by treatment arm (HR, 2.65; 95% CI, 1.37-3.75 with adjuvant imatinib and HR, 1.86; 95% CI, 1.16-2.99 without adjuvant imatinib). When tumor rupture was excluded, this difference in OS between R1 and R0 resections disappeared (HR, 1.05; 95% CI, 0.54-2.01). Conclusions and Relevance: The difference in OS by quality of surgery with or without imatinib was associated with the presence of tumor rupture. When the latter was excluded, the presence of R1 margins was not associated with worse OS. Trial Registration: ClinicalTrials.gov Identifier: NCT00103168.

Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005.

Recent publications have suggested that imatinib (Glivec) may be cardiotoxic. We have therefore assessed the largest study on the agent performed in patients with gastrointestinal stromal tumours, randomising a daily dose of 400mg versus 800 mg. 946 Patients were entered, 942 patients received at least one dose of imatinib. The median time on treatment was 24 months. A total of 24,574 exposure months could be analysed. We could not identify an excess of cardiac events in the study population. In 2 patients (0.2%) a possible cardiotoxic effect of imatinib could not fully be excluded. The current analysis of a large randomised prospective study could not confirm previous suggestions of imatinib induced cardiac toxicity.

Policy statement on multidisciplinary cancer care.

BACKGROUND: Cancer care is undergoing an important paradigm shift from a disease-focused management to a patient-centred approach, in which increasingly more attention is paid to psychosocial aspects, quality of life, patients' rights and empowerment and survivorship. In this context, multidisciplinary teams emerge as a practical necessity for optimal coordination among health professionals and clear communication with patients. The European Partnership for Action Against Cancer (EPAAC), an initiative launched by the European Commission in 2009, addressed the multidisciplinary care from a policy perspective in order to define the core elements that all tumour-based multidisciplinary teams (MDTs) should include. To that effect, a working group conference was held in January 2013 within the EPAAC Work Package 7 (on Healthcare) framework. METHODS: The consensus group consisted of high-level representatives from the following European scientific societies, patient associations and stakeholders: European CanCer Organisation (ECCO), European SocieTy for Radiology & Oncology (ESTRO), European Society for Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), International Society of Geriatric Oncology (SIOG), European Association for Palliative Care (EAPC), European Oncology Nursing Society (EONS), International Psycho-Oncology Society (IPOS),European Cancer Patient Coalition (ECPC), EuropaColon, Europa Donna - The European Breast Cancer Coalition, Association of European Cancer Leagues (ECL), Organisation of European Cancer Institutes (OECI), EUSOMA - European Society of Breast Cancer Specialists, European Hospital and Healthcare Federation (HOPE) and EPAAC Work Packages 5 (Health promotion and prevention), 7, 8 (Research), 9 (Information systems) and 10 (Cancer plans). A background document with a list of 26 core issues drawn from a systematic review of the literature was used to guide the discussion. Five areas related to MDTs were covered: care objectives, organisation, clinical assessment, patients' rights and empowerment and policy support. Preliminary drafts of the document were widely circulated for consultation and amendments by the working group before final approval. RESULTS: The working group unanimously formulated a Policy Statement on Multidisciplinary Cancer Care to define the core elements that should be implemented by all tumour-based MDTs. This document identifies MDTs as the core component in cancer care organisation and sets down the key elements to guide changes across all European health systems. CONCLUSION: MDTs are an essential instrument of effective cancer care policy, and their continued development crucial to providing patients the care they need and deserve. While implementation must remain in local hands, European health systems can still benefit from having a basis for an effective multidisciplinary model of cooperation. This policy statement is intended to serve as a reference for policymakers and healthcare providers who wish to improve the services currently provided to the cancer patients whose lives and well-being depend on their action.

A phase 2 trial of imatinib mesylate in patients with recurrent nonresectable chondrosarcomas expressing platelet-derived growth factor receptor-α or -ß: An Italian Sarcoma Group study.

BACKGROUND: Chondrosarcoma (CS) is a rare and heterogeneous sarcoma in which, after failure of surgery and radiotherapy, chemotherapy plays only a marginal role. Different molecular pathways have been shown to be activated in CS; in particular, both isoforms of platelet-derived growth factor receptor (PDGFR) are expressed and phosphorylated. These observations prompted investigation of the activity of imatinib mesylate (IM) in patients with advanced CS in a phase 2 trial. METHODS: Between January 2007 and June 2009, patients with metastatic, nonresectable CS were treated with 400 mg of IM administered twice daily until disease progression or unacceptable toxicity. Two criteria determined patient trial eligibility: ≥ 1 prior line of chemotherapy and immunohistochemical expression of either PDGFR-α or PDGFR-ß. The primary objective of the trial was objective response. As secondary objectives, the authors selected progression-free survival (PFS) at 4 months, overall survival, and clinical benefit (EUDRACT number 2006-006446-33). RESULTS: Twenty-six patients were enrolled and all demonstrated PDGFR positivity and phosphorylation. No objective response was demonstrated. The 4-month PFS rate was 31% (95% confidence interval [95% CI], 16%-53%). The median overall survival was 11 months (95% CI, 6 months-15 months). Neither long-lasting freedom from disease progression nor clinical benefit was observed. The IM dose was temporarily reduced in 60%15 of the patients because of toxicity. CONCLUSIONS: IM was found to be relatively well-tolerated, but failed to demonstrate meaningful clinical activity in terms of both objective response and freedom from disease progression. Advanced CS remains an incurable disease, and effective targeted therapies are still awaited.