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A randomised trial SHIVA01 compared the efficacy of matched molecularly targeted therapy outside their indications based on a prespecified treatment algorithm versus conventional chemotherapy in patients with metastatic solid tumours who had failed standard of care. No statistical difference was reported between the two groups in terms of progression-free survival (PFS), challenging treatment algorithm. The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) recently defined criteria to prioritise molecular alterations (MAs) to select anticancer drugs. We aimed to retrospectively evaluate the efficacy of matched molecularly targeted agents (MTAs) given in SHIVA01 according to ESCAT tiers. MAs used in SHIVA01 were retrospectively classified into ESCAT tiers, and PFS and overall survival (OS) were compared using log-rank tests. One hundred fifty-three patients were treated with matched MTAs in SHIVA01. MAs used to allocate MTAs were classified into tiers II, IIIA, IIIB and IVA according to the ESCAT. Median PFS was 2.0 months in tier II, 3.1 in tier IIIA, 1.7 in tier IIIB and 3.2 in tier IVA (p = 0.13). Median OS in tier IIIB was worse than that in tiers II, IIIA and IVA (6.3 months versus 11.7, 11.2 and 12.1, p = 0.002). Most MAs used to allocate therapy in SHIVA01 were shown to improve outcomes in other tumour types (tier IIIA). Worst outcome was observed in patients treated based on another type of alteration than the one reported to improve outcomes (tier IIIB), highlighting the crucial impact of the type of the alterations beyond the gene and the signalling pathway. • Most alterations used to allocate therapy in SHIVA01 had low actionability according to the ESMO Scale for Clinical Actionability of molecular Targets. • Worst outcome was reported in patients treated based on another type of alteration than the one reported to improve outcome. • The results highlight the crucial impact of alterations type beyond the gene and/or the signalling pathway. [ABSTRACT FROM AUTHOR]

Abstract: The antiphospholipid syndrome is characterized by recurrent thrombosis and pregnancy morbidity in association with the persistent presence of autoantibodies called antiphospholipid antibodies. Antiphospholipids are a heterogeneous group of circulating autoantibodies associated with a risk of thrombosis and can paradoxically prolong in vitro the clotting times. In the past few years, significant improvement has been made in understanding the pathophysiologic mechanisms of the disease, thus raising the possibility of future predictive test for the risk of thrombosis. The aim of this review is to make an overview on how the antiphospholipids increase the risk of thrombosis and to provide an update of the laboratory diagnosis and the possible future therapies. [Copyright &y& Elsevier]

High throughput molecular screening of solid tumours using core needle biopsies (CNB) allows the identification of actionable molecular alterations. Several reports revealed that success rate of genomic analyses based on CNB is around 70% with failures being mostly related to low proportion of tumour cells. Although several studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to the sensitivity of CNB to detect actionable alterations compared to the less invasive fine needle aspiration (FNA). We aim to prospectively evaluate the ability of FNA to detect molecular alterations identified on CNB in cancer patients (pts) included in SHIVA02 trial. In-house targeted sequencing amplicon based panel (Illumina TSCA 99.3 Kb, 1,504 amplicons covering 87 genes) was used to identify pathogenic variants and gene copy number alterations (CNVs) in both CNB and FNA for pts enrolled in the SHIVA02 trial (NCT03084757). CNB and FNA specimen from 39 pts enrolled in the SHIVA02 trial were assessed. Main tumour locations were breast (17pts, 44%), pancreatic (4pts, 10%), and colorectal cancers (3pts, 8%). 91 somatic variants were identified in both specimens with a good correlation of variants' allelic ratios (r: 0.772). CNV profiles of CNB and FNA were concordant. When taking into account molecular alterations validated during the molecular biology board, 88 alterations (55 variants and 35 CNVs) were reported among which 69 alterations (78%) where concordant between CNB and FNA. Among the 50 actionable alterations, only 12 (3 variants and 9 CNVs) (24%) were discordant between FNA and CNB. Main discordances were related to homozygous deletions and amplifications but false negative results were not related to FNA samples alone (5 CNVs in favour of FNA versus 4 in favour of CNB). Comparative analyses of molecular alterations in CNB compared to FNA showed high concordance in terms of variants as well as CNVs identified. FNA could therefore be easily used in routine diagnostics workflow and clinical trials for tumour molecular screening with the advantage of being minimally invasive. NCT03084757 SHIVA02; Trial release date: April 1, 2017. Institut Curie. MSD Avenir Fundation. C. Le Tourneau: Advisory / Consultancy: MSD, BMS, Merck Serono, AstraZeneca, Novartis, Roche, Nanobiotix. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

SIVHA01 was the first randomized precision medicine trial in patients (pts) with metastatic solid tumors comparing the efficacy of matched MTA outside their indications and conventional chemotherapy in pts with any kind of cancer who had failed standard of care therapy (Le Tourneau et al., Lancet Oncol 2015). No statistical difference was reported between the 2 groups in terms of progression-free survival (PFS), challenging the treatment algorithm used. Several scales of actionability have been developed to address this point, the latest one being the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) that defines clinical evidence-based criteria to prioritize genomic alterations to select MTAs for pts (Mateo et al., Ann Oncol 2018). We aimed to retrospectively evaluate the efficacy of MTAs given in SHIVA01 according to ESCAT. All SHIVA01 molecular alterations targeted were ranked according to ESCAT by assessing the level of evidence reported in the literature, taking into account the tumor type and the administered MTA among 11. PFS and overall survival (OS) according to the ESCAT rank were compared using a log-rank test.All SHIVA01 molecular alterations targeted were ranked according to ESCAT by assessing the level of evidence reported in the literature, taking into account the tumor type and the administered MTA among 11. PFS and overall survival (OS) according to the ESCAT rank were compared using a log-rank test. The 153 pts treated with a MTA in SHIVA01 were included. Molecular alterations were ranked as II, IIIA, IIIB, and IVA according to ESCAT in 38 (25%), 98 (64%), 7 (5%), and 10 pts (7%), respectively. Median PFS was 2.0 months (mo) in tier II, 3.1 mo in IIIA; 1.7 mo in IIIB, and 3.2 mo in IVA (p = 0.13). Median OS was 11.7 mo in tier II, 11.2 mo in IIIA, 6.3 mo in IIIB, and 12.1 mo in IVA (p = 0.002). The majority of molecular alterations taken into account in SHIVA01 were tier IIIA hypothetical targets according to ESCAT. Pts with a tier IIIB molecular alteration had the worst survival, highlighting the crucial impact of the types of molecular alterations beyond the gene and the signaling pathway. Institut Curie. ANR-10-EQPX-03 from the Agence Nationale de le Recherche (Investissements d'avenir) and SiRIC (Site de Recherche Intégré contre le Cancer). All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]