Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.

152 Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment. </jats:p

Association of <i>VEGFA</i> SNP rs2010963 with prognosis and prediction of vascular toxicity of bevacizumab in recurrent glioblastomas.

2028 Background: VEGFA has become an attractive target in high grade gliomas but there is no predictor of response or toxicity to anti-VEGF therapy. We investigated here the association between functional single nucleotide polymorphism (SNP) +405 G&gt;C (rs2010963), located in 5’ untranslated terminal region of VEGFA gene, survival, response to bevacizumab (BVZ), and vascular toxicity. Methods: The rs2010963 was analyzed in blood DNA using a Taqman SNP Genotyping Assay and confronted to Progression Free Survival (PFS), Overall Survival (OS) in the general population of gliomas, and -for the glioblastomas (GBM) treated with BVZ at recurrence- with Response, PFS, and thrombo-hemorragic events. Results: In the general population of 954 gliomas stratified per grade (362 grade 2, 269 grade 3, 323 grade 4) there was no association between rs2010963 and OS or PFS. In the population of 123 recurrent GBM treated with BVZ, we observed a favourable trend in PFS associated with the C allele of rs2010963 (5.4 vs 4.2 months, p = 0.07). Most importantly the CC genotype was associated with the occurrence of thrombo-hemorragic events (6/16 vs 2/107 in CG+GG, p &lt;0.0001). Conclusions: Our data suggest that rs2010963 status has not prognostic significance in gliomas, but is associated with vascular events in recurrent GBM treated with BVZ. The impact of rs2010963 on response to BVZ needs to be further investigated. </jats:p

Angiopoietin-2 May Be Involved in the Resistance to Bevacizumab in Recurrent Glioblastoma

<p>Despite encouraging response rate of bevacizumab (BVZ) in recurrent glioblastoma, many patients do not respond to this schedule and most of the responders develop an early relapse. Plasma concentrations of VEGF, PlGF, Ang2, and sTie2 were assessed by ELISA before and during BVZ treatment in seventy patients. Baseline levels of VEGF-A, and PlGF were higher in patients than in healthy volunteers, whereas no difference was found for Ang2, and sTie2. No biomarker at baseline was associated with response, PFS or OS. At recurrence, the authors observed an increase of Ang2 suggesting that Ang2/sTie2 could be involved in the resistance to BVZ.</p

Enseigner l'architecture en Île-de-France au XXe siècle : une histoire croisée, n°8 (ENSA Paris-Malaquais / Paris-Val de Seine / Paris-La Villette)

International audience3. Éditos // 4. Histoires d'écoles // 11. La primauté de Paris en débat, 1940-1969 : quelle décentralisation pour l'enseignement de l'architecture ? // 17. Révision et hégémonie du système des Beaux-Arts : réformer l’enseignement de l'architecture à l'heure de Vichy // 22. L’enseignement d'André Gutton. Une démarche construite entre l'Institut d'Urbanisme de Paris et l'Ecole des Beaux-Arts (1921-1974) // 29. L'enseignement d'Eugène Beaudouin : entre agence et atelier officiel (1952-1968) // 35. L'atelier Lods, de la volonté de réformer à l'ambition d'une nouvelle école à Paris (1954-1964) // 40. La genèse des ENSA parisiennes : entre libéralisme hérité et autorité contestée // 48. Une tentative de reconfiguration de la carte parisienne des écoles au début des années 1990 : Marne-La-Vallée et Nanterr

Efficacy of AI and palbociclib in ER+ HER2- advanced breast cancer patients relapsing during adjuvant tamoxifen: An exploratory analysis of the PADA-1 trial.

1070 Background: In PADA-1 (NCT03079011), a phase III trial testing the clinical utility of ESR1mut detection, ER+ HER2- advanced breast patients (ABC pts) received Aromatase Inhibitor (AI) and Palbociclib (Pal) +/- LHRH agonist as first line therapy. PADA-1 was open to “AI-sensitive” pts, including those with de novo stage IV disease or metastatic relapse after adjuvant endocrine therapy but also pts with metastatic relapses during adjuvant tamoxifen (TAM). In this subsidiary analysis, we report the efficacy of AI+PAL as first line therapy in patients relapsing on adjuvant TAM. Methods: Main inclusion criteria in PADA-1 are: pre- or post-menopausal pts with ER+ HER2- ABC, who did not receive any prior therapy for ABC and who had no adjuvant AI or completed adjuvant AI for &gt; 12 months or who had disease recurrence while on adjuvant TAM. Results: From 04/2017 to 01/2019, 1017 ABC pts have been included in PADA-1, of which 115 (11.3%) had a metastatic relapse while on adjuvant TAM (TAM only (N = 112) or TAM+GnRH agonist (N = 3)). Median age at inclusion was 46 years (range 25-81), and 58 (50.4%) patients had visceral disease. The median PFS under AI+PAL was 20.4 months (95%CI16.1;27.8) in patients relapsing during adjuvant TAM. In contrast, median PFS in patients with de novo metastatic disease and metastatic relapses after the completion of adjuvant endocrine therapy were 30.6 months (95%CI26.7;Not reached) and 27.8 months (95%CI24.1;30.)], respectively. A subgroup analysis among patients relapsing on adjuvant TAM showed that those relapsing during the first two years of adjuvant TAM had a shorter PFS (11.4 months 95%CI[8.7;20.7]) than those relapsing after 2 years of adjuvant TAM (23.8 months 95%CI[20.2;Not reached]). Conclusions: To our knowledge, these are the first data on first line AI+CDK4/6 inhibitor in patients relapsing on adjuvant TAM. While PFS on AI + PAL appears primarily driven by endocrine resistance status, our data show that AI+PAL is a valuable option also in patients relapsing during adjuvant TAM. Clinical trial information: NCT03079011 . </jats:p

Enseigner l'architecture en Île-de-France au XXe siècle : une histoire croisée, n°8 (ENSA Paris-Malaquais / Paris-Val de Seine / Paris-La Villette)

International audience3. Éditos // 4. Histoires d'écoles // 11. La primauté de Paris en débat, 1940-1969 : quelle décentralisation pour l'enseignement de l'architecture ? // 17. Révision et hégémonie du système des Beaux-Arts : réformer l’enseignement de l'architecture à l'heure de Vichy // 22. L’enseignement d'André Gutton. Une démarche construite entre l'Institut d'Urbanisme de Paris et l'Ecole des Beaux-Arts (1921-1974) // 29. L'enseignement d'Eugène Beaudouin : entre agence et atelier officiel (1952-1968) // 35. L'atelier Lods, de la volonté de réformer à l'ambition d'une nouvelle école à Paris (1954-1964) // 40. La genèse des ENSA parisiennes : entre libéralisme hérité et autorité contestée // 48. Une tentative de reconfiguration de la carte parisienne des écoles au début des années 1990 : Marne-La-Vallée et Nanterr

VEGFA SNP rs2010963 is associated with vascular toxicity in recurrent glioblastomas and longer response to bevacizumab

Although anti-VEGF therapy is widely used in high-grade gliomas, no predictor of response or toxicity has been reported yet. We investigated here the association of the functional single nucleotide polymorphism (SNP) rs2010963, located in the 5' untranslated terminal region of the VEGFA gene, with survival, response to bevacizumab (BVZ) and vascular toxicity. The rs2010963 was genotyped by Taqman assay in blood DNA from 954 glioma patients with available survival data, including 225 glioblastoma (GBM) patients treated with BVZ. VEGFA plasma levels were assessed by ELISA in 87 patients before treatment. Thrombo-hemorragic adverse events were recorded during BVZ treatment or not, and in an independent population of 92 GBM patients treated with temozolomide. The CC genotype was associated with the occurrence of thrombo-hemorragic events (CC 25 versus CG 13.5 and GG 5.2 %; P = 0.0044) during BVZ. A similar but weaker and non significant trend was observed in patients not receiving BVZ. A CC genotype was associated with higher levels of plasma VEGFA at baseline (107.6 versus 57.50 pg/mL in heterozygotes (CG) and 52.75 pg/mL in GG patients, P = 0.035 and P = 0.028 respectively). The CC genotype tended to be associated to longer PFS when treated with BVZ (P = 0.05), but not when treated with the temozolomide treatment. Our data suggest that the rs2010963 genotype is associated with longer PFS, higher risk of vascular events in recurrent GBM especially treated with BVZ, and higher plasma VEGFA concentration. It may help to identify patients at risk of vascular adverse events during BVZ treatment