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Background: Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib.Methods: This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion.Results: Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8-4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%).Conclusions: The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing.Trial Registration: ClinicalTrials.gov NCT01735968 (date of initial registration 28/11/2012). [ABSTRACT FROM AUTHOR]

Background: The Sarcoma Policy Checklist was created by a multidisciplinary expert group to provide policymakers with priority areas to improve care for sarcoma patients.Main Body: This paper draws on this research, by looking more closely at how France, Germany, Italy, Spain, Sweden and the United Kingdom are addressing each of these priority areas. It aims to highlight key gaps in research, policy and practice, as well as ongoing initiatives that may impact the future care of sarcoma patients in different European countries. A pragmatic review of the published and web-based literature was undertaken. Telephone interviews were conducted in each country with clinical and patient experts to substantiate findings. Research findings were discussed within the expert group and developed into five core policy recommendations. The five identified priority areas were: the development of designated and accredited centres of reference; more professional training; multidisciplinary care; greater incentives for research and innovation; and more rapid access to effective treatments. Most of the countries studied have ongoing initiatives addressing many of these priorities; however, many are in early stages of development, or require additional funding and resources.Conclusion: Gaps in access to quality care are particularly concerning in many of Europe's lower-resourced countries. Equitable access to information, clinical trials, innovative treatments and quality specialist care should be available to all sarcoma patients. Achieving this across Europe will require close collaboration between all stakeholders at both the national and European level. [ABSTRACT FROM AUTHOR]