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Item does not contain fulltext, BACKGROUND AND AIMS: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series. METHODS: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination. RESULTS: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients. CONCLUSIONS: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.

SP142 programmed cell death ligand 1 (PD-L1) status predicts response to atezolizumab in triple-negative breast carcinoma (TNBC). Prevalence of VENTANA PD-L1 (SP142) Assay positivity, concordance with the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay, and association with clinicopathologic features were assessed in 447 TNBCs. SP142 PD-L1 intraobserver and interobserver agreement was investigated in a subset of 60 TNBCs, with scores enriched around the 1% cutoff. The effect of a 1-hour training video on pretraining and posttraining scores was ascertained. At a 1% cutoff, 34.2% of tumors were SP142 PD-L1 positive. SP142 PD-L1 positivity was significantly associated with tumor-infiltrating lymphocytes (P <0.01), and node negativity (P=0.02), but not with tumor grade (P=0.35), tumor size (P=0.58), or BRCA mutation (P=0.53). Overall percentage agreement (OPA) for intraobserver and interobserver agreement was 95.0% and 93.7%, respectively, among 5 pathologists trained in TNBC SP142 PD-L1 scoring. In 5 TNBC SP142 PD-L1-naive pathologists, significantly higher OPA to the reference score was achieved after video training (posttraining OPA 85.7%, pretraining OPA 81.5%, P<0.05). PD-L1 status at a 1% cutoff was assessed by SP142 and SP263 in 420 cases, and by SP142 and 22C3 in 423 cases, with OPA of 88.1% and 85.8%, respectively. The VENTANA PD-L1 (SP142) Assay is reproducible for classifying TNBC PD-L1 status by trained observers; however, it is not analytically equivalent to the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

SP142 programmed cell death ligand 1 (PD-L1) status predicts response to atezolizumab in triple-negative breast carcinoma (TNBC). Prevalence of VENTANA PD-L1 (SP142) Assay positivity, concordance with the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay, and association with clinicopathologic features were assessed in 447 TNBCs. SP142 PD-L1 intraobserver and interobserver agreement was investigated in a subset of 60 TNBCs, with scores enriched around the 1% cutoff. The effect of a 1-hour training video on pretraining and posttraining scores was ascertained. At a 1% cutoff, 34.2% of tumors were SP142 PD-L1 positive. SP142 PD-L1 positivity was significantly associated with tumor-infiltrating lymphocytes (P <0.01), and node negativity (P=0.02), but not with tumor grade (P=0.35), tumor size (P=0.58), or BRCA mutation (P=0.53). Overall percentage agreement (OPA) for intraobserver and interobserver agreement was 95.0% and 93.7%, respectively, among 5 pathologists trained in TNBC SP142 PD-L1 scoring. In 5 TNBC SP142 PD-L1-naive pathologists, significantly higher OPA to the reference score was achieved after video training (posttraining OPA 85.7%, pretraining OPA 81.5%, P<0.05). PD-L1 status at a 1% cutoff was assessed by SP142 and SP263 in 420 cases, and by SP142 and 22C3 in 423 cases, with OPA of 88.1% and 85.8%, respectively. The VENTANA PD-L1 (SP142) Assay is reproducible for classifying TNBC PD-L1 status by trained observers; however, it is not analytically equivalent to the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay.

Background: TNBC, an aggressive subtype of breast carcinoma, has limited treatment options. Improved progression free and overall survival has been observed in patients with unresectable locally advanced and metastatic TNBC (NCT02425891) with atezolizumab and nab-paclitaxel in PD-L1-positive [>=1% on immune cells using VENTANA SP142 PD-L1 IHC]. Although this predictive marker is pivotal for treatment decision making, there are limited data on inter- and intra-pathologist (P) agreement for SP142 PD-L1 scoring. We investigated reproducibility of SP142 IHC in TNBC amongst Ps trained in SP142 scoring and the effect of training on accuracy of assessment by Ps untrained in PD-L1. Method(s): Previously untreated, resected primary invasive TNBCs were collected from 4 centers. SP142 PD-L1 IHC was performed on tissue microarrays. 60 cases, selected for PD-L1 expression close to 1% cut-off, were dichotomized as negative (<1%) or positive (>=1%). Intra- and inter-observer reproducibility assessment involved 10 Ps, conducted over 2 days (D). Five Ps were previously trained in SP142 IHC (subgroup - SG1) and 5 were SP142 assessment naive (SG2). SG2 received 1 hour of training in SP142 IHC prior to scoring on D2; pre- and post-training scores were compared. Intra-observer reproducibility was evaluated by comparing the scores obtained by SG1 on D1 and D2. Inter-observer reproducibility compared scores between SG1 on D1. Result(s): High intra-observer agreement was demonstrated between SG1; overall percent agreement (OPA) 95.0% (95% CI 91.9- 97.0), average positive agreement (APA) 95.2% (95% CI 92.2 - 97.0), average negative agreement (ANA) 94.9% (95% CI 91.7 - 96.9), Cohen's kappa co-efficient (K) = 0.90. Inter-observer agreement was also high; OPA 93.3% (95% CI 91.1 - 95.1), APA 93.7% (95% CI 91.5 - 95.3), ANA 93.0% (95% CI 90.6 - 94.8), K = 0.87. Following D2 training, SG2 demonstrated significant improvement in SP142 agreement; OPA D1 81.5% (95% CI 76.8 - 85.5); D2 85.7% (95% CI