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Atezolizumab is an inhibitor of PD-L1, which can lead to enhanced anticancer T-cell activity. We aimed to evaluate the safety, pharmacokinetics, and activity of atezolizumab in children and young adults with refractory or relapsed solid tumours, with known or expected PD-L1 expression.iMATRIX was a multicentre, open-label, phase 1-2 trial of patients (aged30 years) with solid tumours or lymphomas recruited from 28 hospitals in ten countries (USA, France, Italy, UK, Spain, the Netherlands, Denmark, Israel, Switzerland, and Germany). Eligible patients younger than 18 years received 15 mg/kg atezolizumab (maximum 1200 mg); patients aged 18-29 years received the adult dose (1200 mg) until disease progression or loss of clinical benefit. Co-primary endpoints were safety (assessed by incidence of adverse events) and pharmacokinetics (assessed by serum atezolizumab concentrations). Secondary endpoints included the proportion of patients achieving an objective response. This trial is registered with ClinicalTrials.gov, number NCT02541604.Between Nov 5, 2015, and April 2, 2018, we screened 115 patients, 25 of whom did not meet the inclusion criteria. 90 patients, with a median age of 14 years (IQR 10-17), were enrolled. At the data cutoff (April 2, 2018), two patients remained on study treatment. 87 (97%) of 90 patients received at least one dose of atezolizumab at 15 mg/kg or 1200 mg and were evaluable for safety. Three patients were not treated owing to either poor clinical condition or withdrawal of consent. In the safety-evaluable population (n=87), the most common adverse events were pyrexia (36 [41%] patients) and fatigue (31 [36%]). The most common grade 3-4 adverse event was anaemia (19 [22%] patients). The most commonly reported serious adverse events were in the categories of infections and infestations; pyrexia was the only serious adverse event reported in more than two patients. 57 (66%) patients had at least one treatment-related adverse event (grade 1-4); fatigue was the most common treatment-related adverse event (17 patients [20%]). There were no fatal adverse events. Mean serum concentrations of atezolizumab were overlapping and comparable between children receiving 15 mg/kg and young adults receiving 1200 mg of atezolizumab every 3 weeks. Serum concentrations of atezolizumab were above the target exposure level in all patients. At 6 months, four patients (5%) achieved an objective response (all partial responses).Although response to atezolizumab was restricted, atezolizumab was well tolerated with generally comparable exposure across populations. Our findings might help to define future development strategies for immune checkpoint inhibitors either by focusing research to specific disease subpopulations that exhibit greater benefit from immune checkpoint inhibitors, or by providing the means to identify therapeutic combination partners that augment T-cell infiltration and proliferation in so-called immune cold tumour microenvironments.F Hoffmann-La Roche.

Background: Atezolizumab targets programmed death-ligand 1 (PD-L1), leading to enhanced anticancer T-cell activity. The iMATRIX-atezolizumab study (phase 1/2, multicentre, open-label; NCT02541604) is the first trial to evaluate the safety, pharmacokinetics, and activity of atezolizumab in paediatric/young adult patients with refractory/relapsed solid tumours, with known or expected PD-L1 expression. Methods: Patients received atezolizumab on day 1 of each 3-week cycle until disease progression (PD)/loss of clinical benefit. Patients

Objective.Direct costs of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) have not been well characterized in the United States. This study assessed healthcare resource use and direct cost of AS and PsA, and identified predictors of all-cause medical and pharmacy costs.Methods.Adults aged ≥ 18 with a diagnosis of AS and PsA were identified in the MarketScan databases between October 1, 2011, and September 30, 2012. Patients were continuously enrolled with medical and pharmacy benefits for 12 months before and after the index date (first diagnosis). Baseline demographics and comorbidities were identified. Direct costs included hospitalizations, emergency room and office visits, and pharmacy costs. Multivariable regression was used to determine whether baseline covariates were associated with direct costs.Results.Patients with AS were younger and mostly men compared with patients with PsA. Hypertension and hyperlipidemia were the most common comorbidities in both cohorts. A higher percentage of patients with PsA used biologics and nonbiologic disease-modifying drugs (61.1% and 52.4%, respectively) compared with patients with AS (52.5% and 21.8%, respectively). Office visits were the most commonly used resource by patients with AS and PsA (∼11 visits). Annual direct medical costs [all US dollars, mean (SD)] for patients with AS and PsA were $6514 ($32,982) and $5108 ($22,258), respectively. Prescription drug costs were higher for patients with PsA [$14,174 ($15,821)] compared with patients with AS [$11,214 ($14,249)]. Multivariable regression analysis showed higher all-cause direct costs were associated with biologic use, age, and increased comorbidities in patients with AS or PsA (all p < 0.05).Conclusion.Biologic use, age, and comorbidities were major determinants of all-cause direct costs in patients with AS and PsA.

Pain, itching, burning and irritation are common symptoms of psoriasis but have not been well characterized by overall psoriasis severity.Using 2012 syndicated psoriasis patient survey data, 1050 subjects were classified into mild (n = 610) and moderate-to-severe (n = 440) psoriasis severity groups based on self-reporting. Demographics, comorbid medical conditions and patient-reported key symptoms (i.e. flare-up frequency, psoriasis-related pain, itching, burning, hurting, irritation) were compared between groups. Multiple regressions were employed to examine the impact of overall psoriasis severity on each key symptom, controlling for demographics and comorbidities.Mild patients were older; more than 20% in both groups had joint pain and depression. Over 35 and 68% of the moderate-to-severe patients reported severe pain between or during flare-ups, respectively, and over 79% reported frequent bothersome itching. Controlling for between-group differences, moderate-to-severe patients had worse pain, were more likely to have continual flare-ups (odds ratio = 3.0) and flare-ups more than once monthly (odds ratio = 3.0), and reported more bothersome symptoms than patients with mild disease (all p 0.05).The presence and level of particular symptoms increase with self-reported disease severity in patients with psoriasis. Careful investigation of symptoms in tandem with clinical observation is important for effective psoriasis management.

Introduction The iMATRIX-atezo trial (NCT02541604) assessed the safety and pharmacokinetics (primary objectives) and preliminary activity (secondary objective) of atezolizumab in pediatric and young adult patients with refractory/relapsed solid tumors, including Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Atezolizumab targets PD-L1 expressed by tumor cells leading to an enhanced anticancer T-cell response. The purpose of this analysis was to investigate the association between PD-L1 expression and response to atezolizumab in patients participating in the iMATRIX-atezo trial. Methods Patients aged Results Eighty-seven patients received ≥1 dose of atezolizumab. Of 11 patients with high PD-L1 expression (TC2/TC3/IC2/IC3) and response data, four had a partial response (PR; two with HL, one with NHL, one with a rhabdoid tumor), one had stable disease (SD) and six had progressive disease (PD). Of 52 patients with low or no PD-L1 expression (TC1/TC0/IC1/IC0) and response data, no responses were observed. Though numerically limited, PD-L1 expression and response were significantly correlated (p=0.0006, Fisher’s exact test). HL (8/9 patients) and NHL (2/3 patients) cohorts had the greatest proportion of patients with high baseline PD-L1. Levels of CD8+ (T cells), CD20+ (B cells) and stromal TILs at baseline were significantly associated with patients’ response status (p Conclusions High PD-L1 expression compared with low or no expression was associated with a greater response to atezolizumab, notably in patients with HL and NHL. Despite small sample sizes and limited responses, these biomarker data support adult studies citing the association between PD-L1 and response to atezolizumab; data suggest that PD-L1 may also be a predictor of atezolizumab response in pediatric and young adult patients. Citation Format: Katherine E. Hutchinson, Minlei Liao, Mufiza Farid-Kapadia, Francis Donaldson, Nga Wan Rachel Tam, Lingyan Helen Fu, Meghna Das Thakur, C. Michel Zwaan, Birgit Geoerger, Lynley V. Marshall, Tanya Trippett, Gianluca Rossato. Correlation between response to atezolizumab and PD-L1 tumor expression in pediatric and young adult patients enrolled in the phase I/II iMATRIX-atezo study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3114.

Background Cluster analysis (CA) is a frequently used applied statistical technique that helps to reveal hidden structures and “clusters” found in large data sets. However, this method has not been widely used in large healthcare claims databases where the distribution of expenditure data is commonly severely skewed. The purpose of this study was to identify cost change patterns of patients with end-stage renal disease (ESRD) who initiated hemodialysis (HD) by applying different clustering methods. Methods A retrospective, cross-sectional, observational study was conducted using the Truven Health MarketScan® Research Databases. Patients aged ≥18 years with ≥2 ESRD diagnoses who initiated HD between 2008 and 2010 were included. The K-means CA method and hierarchical CA with various linkage methods were applied to all-cause costs within baseline (12-months pre-HD) and follow-up periods (12-months post-HD) to identify clusters. Demographic, clinical, and cost information was extracted from both periods, and then examined by cluster. Results A total of 18,380 patients were identified. Meaningful all-cause cost clusters were generated using K-means CA and hierarchical CA with either flexible beta or Ward’s methods. Based on cluster sample sizes and change of cost patterns, the K-means CA method and 4 clusters were selected: Cluster 1: Average to High (n = 113); Cluster 2: Very High to High (n = 89); Cluster 3: Average to Average (n = 16,624); or Cluster 4: Increasing Costs, High at Both Points (n = 1554). Median cost changes in the 12-month pre-HD and post-HD periods increased from $185,070 to $884,605 for Cluster 1 (Average to High), decreased from $910,930 to $157,997 for Cluster 2 (Very High to High), were relatively stable and remained low from $15,168 to $13,026 for Cluster 3 (Average to Average), and increased from $57,909 to $193,140 for Cluster 4 (Increasing Costs, High at Both Points). Relatively stable costs after starting HD were associated with more stable scores on comorbidity index scores from the pre-and post-HD periods, while increasing costs were associated with more sharply increasing comorbidity scores. Conclusions The K-means CA method appeared to be the most appropriate in healthcare claims data with highly skewed cost information when taking into account both change of cost patterns and sample size in the smallest cluster.

Objective: Limited information exists on real-world use of anti-tumor necrosis factor-α (TNFα) biologic agents in ankylosing spondylitis (AS). This study evaluated the treatment patterns and costs of anti-TNFα biologic therapy and disease-modifying antirheumatic drugs (DMARDs) in patients with AS. Methods: MarketScan claim databases were used to identify anti-TNFα biologic treatment-naive AS patients (aged ≥ 18 years that had not undergone anti-TNFα biologic therapy in the previous 6 months) who initiated anti- TNFα biologic treatment between October 1, 2009 and September 30, 2010. Frequency of anti-TNFα biologic switching, duration, treatment modification, and medical and pharmacy drug costs for each line of anti-TNFα biologic therapy was analyzed during the 3-year follow-up. Results: We identified 337 eligible patients with AS. First-line anti-TNFα biologics were: etanercept (n=115), adalimumab (n=129), infliximab (n=38), and golimumab (n=15). Patients who did not switch were persistent with their first-line agent for a longer duration (505 days) than those who switched to a second-line (336 days) or thirdline (325 days) anti-TNFα biologic agent. Time to first treatment modification was shorter for those who switched to second-line (88 days) and third-line 6 days) therapy versus those who remained on first-line therapy (160 days). Monthly per member medical costs were greatest for nonswitchers ($354) than for patients who received secondline ($225) or third-line ($112) anti-TNFα biologic treatment. Overall pharmacy drug costs were similar for patients with first-line ($1899), second-line ($1955) or third-line and further ($1890) therapy. Conclusion: Patients with AS who switched anti-TNFα biologic therapy had more modifications to their treatment during the follow-up period. Those who switched to second- or third-line anti-TNFα biologic therapy had lower medical costs compared with those who remained with first-line treatment; however, pharmacy costs were similar among all.

Background Real-world data regarding anti-tumor necrosis factor alpha (anti-TNFα) biologic therapy use in psoriatic arthritis (PsA) are limited; therefore, we described treatment patterns and costs of anti-TNFα therapy in PsA patients in the United States. Methods PsA patients (N = 990) aged ≥18 years who initiated anti-TNFα therapy were selected from MarketScan claims databases (10/1/2009 to 9/30/2010). Number of patients on first- (n = 881), second- (n = 72), or third- or greater (n = 37) line of anti-TNFα therapy, persistence, time-to-switch or modification, pharmacy and medical costs (measured per patient per month [PPPM]) for each line of therapy were observed during the 3-year follow-up. Results PsA patients receiving only one line of anti-TNFα therapy remained on first-line for ~17 months while those who switched to second- or third- or greater persisted on first-line for ~11 to 12 months, respectively. Time to first-line modification was longer for patients who switched to third- or greater line therapy (7 months) than those who did not switch or switched to second-line (range, ~2 to 4 months). Time-to-switch and time to first-line modification was progressively shorter with each line of therapy for patients who received third- or greater line. PPPM medical costs were higher for patients who did not switch ($322) than those who switched to second- ($167) or third- or greater ($217) line. PPPM pharmacy costs were greater for patients with third- or greater line therapy ($2539) than those who did not switch ($1985) or switched to second-line ($2045). Conclusion While the majority of patients received only one line of anti-TNFα therapy, a subset of patients switched to multiple lines of therapy during the 3-year follow-up period. Persistence and therapy modifications differed between these patients and those receiving only one line. Overall medical costs were highest for patients who did not switch, and pharmacy costs increased as patients switched to each new line of therapy.