Clinical experience with sunitinib (SU) in patients over age 65 with metastatic gastrointestinal stromal tumors (GIST): A retrospective study from the French Sarcoma Group (FSG).

10546 Background: Elderly GIST patients (pts) represent a consistent portion of all GIST pts, but are under-represented in clinical trials. Data on benefits, tolerance of SU in elderly GIST pts and their specific outcome are very limited. Methods: Charts of elderly pts (≥ 65 yrs)treated with SU in routine clinical practice from 11 Centres of the FSG were reviewed to evaluate the efficacy and safety of SU. Results: 71 elderly GIST pts were reviewed, with a median age of 74, [distributed as 65-74, n=36; 75-84, n=30; ≥ 85, n=5], 41 (57%) men, with median ECOG-PS= 1 (0-2), and median active comorbities of 1 (0-4). SU was administered after progression on first-line Imatinib (400 mg/d for 21 pts, 400 then 800 mg/d for 45 pts) or masitinib (5 pts). SU was started at 50 mg/d 4-wks-on/2 wks-off in 37 pts (52%), at 37.5 mg daily in 32 pts (45%), and at 25 mg daily in 2 pts. All but 2 pts experienced at least one adverse event (AE). Drug related AE were mainly of grade 1 or 2 (298/388, 76%), and medically manageable. Most frequent AE were fatigue (20%), diarrhea (11%), mucositis (7%), abdominal pain (7%), hand-foot syndrome (6%), neutropenia (6%), and hypertension (5%). Permanent dose reduction was reported in 33 pts (46%). In 17 pts (24%) SU was permanently stopped due to grade 3 or 4 AE. ; this occurred within 3 months after starting SU in 10 pts. At a median 36 months follow-up, 53 pts progressed, and 28 pts were alive. The median PFS and OS were 10.2 (0.2-54) and 21 (0.5-77) months, respectively. Univariate analysis showed that age (≤ 80), PS (&lt;1), WBC (≤ 4 Giga/l), Hb and Albumin have a positive impact on OS (all p &lt; 0.04) and PFS (all p &lt; 0.05). In multivariate analysis, Albumin and Hb had an impact on OS and PFS, PS had an impact only on OS, and WBC only on PFS. A correlation was found between comorbidities and Grade 3/4 toxicities, but no correlation between any toxicities and outcome. Conclusions: Compared to data from clinical trials, SU yields similar rates of GIST control and OS in elderly pts despite frequent dose reductions or interruptions. Since comorbidities may increase the risks of AEs, careful follow-up to assess tolerance is particularly indicated in elderly GIST pts. </jats:p

Phase II study of sorafenib mesylate (So) in patients (pts) with evolutive and advanced epithelioid hemangioendothelioma (EHE) or hemangiopericytoma/solitary fibrous tumor (SFT).

10020 Background: There is no standard of care for both rare sarcomas. Regarding, the important vascularization of EHE and SFT, we explored the activity/toxicity of So in pts with these sarcomas. Methods: We conducted a multicenter one-step phase II trial of So (800 mg/d). The primary endpoint was the 9-months progression-free rate (9-PFR). According to EORTC criteria, So is considered as promising drug if 6-PFR≥14%. All pts have had documented progressive disease at entry. Results: 20 pts (15 EHE &amp; 5 SFT) were enrolled from June 2009 to February 2011 in the 8 participating institutions. 12 men and 8 women. Median age was 57. The most common primaries were superficial trunk (8 cases) and liver (4 cases). PS were 0 in 10 cases, 1 in 7 cases and 2 in 3 cases. 16 pts had metastasic disease , especially in lung (15), liver (6) and bone (4). Eight pts received prior chemotherapy (Doxorubicin : n= 8 cases and taxane : n =3). The median So treatment duration was 124 days. 9 pts experienced grade-3 toxicities; the most frequent grade-3 toxic events were hand foot syndrome (5 pts), myalgia (1), stomatitis (1), anorexia (1), diarrhea (1) and arterial hypertension (1).Because of this toxicity, treatment discontinuation was necessary in 6 cases and dose reduction was necessary in 5 pts. The 9-PFR was 6/18 (33.3% [11.5-55.1]). The 2, 4 and 6 PFR were 15/18 (83.3%), 8/18 (44.4%) and 7/18 (38.8) respectively We observed 2 partial responses lasting 2 and 9 months in 2 pts with EHE. Analysis of the predictive value of circulating pre-angiogenetic biomarkers is ongoing. Conclusions: According to the STBSG-EORTC criteria (3-PFR≥40% &amp; 6-PFR≥14%), So is a promising drug for EHE and SFT pts. Further trials is needed, especially a discontinuation randomized trial. </jats:p

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup