STELLAR Trial Research Articles

1851P - Tumor treating fields plus chemotherapy for first-line malignant pleural mesothelioma (MPM): Radiological responses in the STELLAR trial

BackgroundTumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor. TTFields have significantly extended survival of patients with glioblastoma. In vitro, human MPM cells are highly susceptible to TTFields. In the phase 2 STELLAR study [NCT02397928], patients with unresectable MPM treated with first line chemotherapy in combination with TTFields had a significantly higher median overall survival compared with historical controls (18.2 Vs. 12.1 months). We report on radiological data from STELLAR patients whose tumors responded while receiving the combined therapy. MethodsThe STELLAR trial accrued 80 patients with unresectable, previously untreated MPM. Patients received continuous 150kHz TTFields (>18h/day) combined with pemetrexed and cisplatin or carboplatin (standard dosing). Inclusion criteria: ECOG PS of 0-1, pathologically proven MPM and > measurable lesion per modified RECIST. Patients were followed q3w (CT scan q6w) until disease progression. Radiological assessments were done 6-weekly at study sites. ResultsPartial responses (PRs) were seen in 40.3% (29/72) of evaluable patients and clinical benefit (PR+SD) was seen in 97.2% (70/72) patients. The median time between treatment start and PR was 1.9 months (range: 1.4-4.4 months). All patients presenting with PR during the STELLAR study had continuous reduction in the total sum of lesion diameters, suggesting no initial/pseudo-progression. 83% of the patients who responded to the combined therapy finally had disease progression with a median response duration of 5.7 months (range: 1.4-13 months). One patient did not progress for more than 27 months. 28 responders (97%) reported at least 1 adverse event, and 7 patients (24%) had TTFields-related skin toxicities. ConclusionsThe STELLAR study significantly extended survival in previously untreated MPM patients. Response rates were similar to those reported for the current MPM standard of care treatment, but were of longer duration with the addition of TTFields. The only TTFields-related adverse event was skin irritation beneath the arrays. Clinical trial identificationNCT02397928. Legal entity responsible for the studyNovocure. FundingNovocure. DisclosureF. Grosso: Travel / Accommodation / Expenses: Novocure. G.L. Ceresoli: Travel / Accommodation / Expenses: Novocure.

Clinical Value of TTFields Treatment in Mesothelioma Using ASCO and ESMO Frameworks

The potential effectiveness and safety of TTFields in addition to pemetrexed and cisplatin or carboplatin in malignant pleural mesothelioma (MPM) was recently shown by the analysis of the phase II single arm EF-23 STELLAR trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in MPM by applying ASCO and ESMO frameworks to the comparison of the STELLAR data to historical controls. The EF-23 STELLAR Trial (n=80) demonstrated that adding TTFields to pemetrexed and cisplatin or carboplatin for malignant pleural mesothelioma patients resulted in overall survival of 18.2 months (95% CI 12.1-25.8) and progression free survival of 7.6 months (95% CI 6.7-8.6). The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks were applied to the EF-23 trial data using a historical control as comparator. The application of the ASCO framework to the EF-23 data resulted in a NHB score of 52. This result was at the higher end of the score range of novel cancer treatments and compares well to the results for nivolumab in advanced non-squamous NSCLC and advanced squamous NSCLC as reference points. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced) which would be the first score reported for MPM. The MCBS scores of A/5 are the highest scores achievable in the ESMO framework, and higher than the ESMO MCBS scores reported in the literature for NSCLC treatments. Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to Pemetrexed and Cisplatin or Carboplatin in malignant pleural mesothelioma patients provides a significant clinical benefit. The high scores underline the fact that treatment with TTFields may extend progression free and overall survival without additional systemic toxicities.

Radiological Response Patterns in Malignant Pleural Mesothelioma (MPM): Subgroup Analyses of the Phase 2 Stellar Trial of TTFields Plus Chemotherapy for First-Line Treatment

Radiological Response Patterns in Malignant Pleural Mesothelioma (MPM): Subgroup Analyses of the Phase 2 Stellar Trial of TTFields Plus Chemotherapy for First-Line Treatment

Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials

Accurate noninvasive tests (NITs) are needed to replace liver biopsy for identifying advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). We analyzed screening data from two phase 3 trials of selonsertib to assess the ability of NITs to discriminate advanced fibrosis. Centrally read biopsies from the STELLAR studies, which enrolled patients with bridging fibrosis and compensated cirrhosis, were staged according to the NASH Clinical Research Network classification. We explored associations between fibrosis stage and NITs, including the nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness by vibration-controlled transient elastography (LS by VCTE). The performance of these tests to discriminate advanced fibrosis, either alone or in combinations, was evaluated using areas under the receiver operating characteristic curve (AUROCs) with 5-fold cross-validation repeated 100 times. Of the 4,404 patients screened for these trials, 3,202 had evaluable biopsy data: 940 with F0-F2 fibrosis and 2,262 with F3-F4 fibrosis. Significant differences between median values of NITs for patients with F0-F2 versus F3-F4 fibrosis were observed: -0.972 versus 0.318 for NFS, 1.18 versus 2.20 for FIB-4, 9.22 versus 10.39 for ELF, and 8.8 versus 16.5 kPa for LS by VCTE (all P<0.001). AUROCs ranged from 0.75 to 0.80 to discriminate advanced fibrosis. FIB-4 followed by an LS by VCTE or ELF test in those with indeterminate values (FIB-4 between 1.3 and 2.67) maintained an acceptable performance while reducing the rate of indeterminate results. Conclusion: Among patients being considered for enrollment into clinical trials, NITs alone or in combination can reduce the need for liver biopsy to discriminate advanced fibrosis caused by NASH. The predictive value of these tests for general screening will require confirmation in a real-world population.

Abstract LB-160: Glioblastoma and mesothelioma: Do estimates of health state utilities compare in rare cancers treatable with tumor treating fields

Abstract Objective: To compare the estimated health state utilities of glioblastoma (GBM) and malignant pleural mesothelioma (MPM) given that they are both rare cancers treatable with tumor treating fields (TTFields) Background: Glioblastoma (GBM) is the most aggressive form of primary brain cancer in adults. MPMis an invasive and generally fatal malignancy of the lung mainly caused by exposure to asbestos fibers. To understand the comparative economic value of new treatments, the quality-adjusted life year (QALY) has been developed and is widely used in health economic literature. Given that GBM and MPM are both rare and aggressive cancers, both potentially treatable with TTFields, we aimed to understand whether the estimated health state utilities for each disease state were comparable. Clinical results show a comparable effect on median overall survival (OS). The EF-14 Trial showed that the addition of TTFields treatment increases median OS by 4.9 months in GBM, while the EF-23 showed that TTFields adds a median OS of 6.1 months compared to historical control in MPM. Differing health state utilities by disease, in this case a central nervous system tumor versus a pleural tumor, could influence the adoption of a new treatment regardless of whether the efficacy and safety of that new treatment is comparable for both disease states. Methods: We reviewed the structure and results of the EF-14 and STELLAR trials. We determined the appropriate health states for evaluation in both diseases as stable disease, progressed disease, and death. We then performed a comprehensive review of the published literature regarding health utility values in GBM and MPM patients using a boolean search in the Medline database. The estimated health state utilities were then compared by disease. Results: All publications that reference health utilities for GBM are derived from the same source. Estimates of utility were obtained from the NHS Value of Health Panel (VoHP) and based on the standard gamble method for preference elicitation, rating a total of nine descriptive health state scenarios. Utilities for stable disease in glioblastoma were 0.85 and 0.73 for progressed disease as a base case respectively. The estimates for MPM utilities were obtained using varying methods not correlated to stable or progressive disease. One method elicited utilities describing 243 distinct states from the EQ-5 questionnaire data collected during the trial at an indiviual patient level. Conclusions: Health utility estimates published so far for GBM are not comparable to the helth utilities published and used for MPM. While the utilities in GBM are scarce, but allow for use in a three health state disease model, utilities for MPM are more diverse and do at the moment not support a health state model. MPM utilities elicited from the EQ-5 however describe more adequately the individual utilities and their change during the course of the disease. The lack of such detailed utilities e.g. in GBM could lead to disparities in the assessment of cost effectiveness of new treatments like tumor treating fields for different indications, despite similar costs and clinical efficacy. Citation Format: Christina Proescholdt, Justin Kelly. Glioblastoma and mesothelioma: Do estimates of health state utilities compare in rare cancers treatable with tumor treating fields [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 LB-160.

Abstract CT201: Final results of Phase II STELLAR trial: TTFields with chemotherapy in unresectable malignant pleural mesothelioma

Abstract Background Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields plus chemotherapy have significantly extended survival in glioblastoma. Method Patients (n= 80) with unresectable, previously untreated mesothelioma were treated with continuous 150 kHz TTFields (&amp;gt;18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria: ECOG PS 0-1, pathologically proven mesothelioma and at least one measurable lesion per modified RECIST criteria. The primary endpoint was overall survival (OS) and secondary endpoints were response rate, progression free survival (PFS) and toxicity. EOCG status and cancer-related pain were assessed until disease progression using a visual analog scale. This prospective, single arm study assumed an historical control with a median survival of 12.1 months (Vogelzang, JCO. 2003). The sample size provides 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months. Result All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. The 1-year survival rate was 62.2% (95% CI 50.3-72.0). Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). Clinical benefit (PR+SD) was seen in 97.2% of patients. ECOG score was stable during the first year of follow up. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy. 63% (50 patients) received carboplatin. Median time to deterioration in performance status was 13.1 months. Average pain score was lower compared to baseline during the first 7 months of treatment and higher later with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis. Grade 3-4 systemic AEs were reported in &amp;gt;3% of patients: hematological AEs (15%) and fatigue (4%). Conclusion The study met its primary endpoint of significant extension of survival in previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for TTFields plus standard chemotherapy to the thorax. The use of the TTFields was not associated with a decrease in performance status or an increase in pain. TTFields in combination with chemotherapy are efficacious in malignant pleural mesothelioma vs chemotherapy alone in historical data. Citation Format: Giovanni Luca Ceresoli, Joachim Aerts, Jaroslaw Madrzak, Rafal Dziadziuszko, Rodryg Ramlau, Susana Cedres, Birgitta Hiddinga, Jan VanMeerbeeck, Manlio Mencoboni, David Planchard, Antonio Chella, Lucio Crino, Maciej Krzakowski, Federica Grosso. Final results of Phase II STELLAR trial: TTFields with chemotherapy in unresectable malignant pleural mesothelioma [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 CT201.

Abstract LB-161: Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma

Abstract Objective: To assess the clinical value of tumor treating fields (TTFields) in malignant pleural mesothelioma (MPM) by means of the ASCO and ESMO frameworks. Background: The potential effectiveness and safety of TTFields in addition to pemetrexed and cisplatin or carboplatin in MPM was recently shown by the analysis of the Phase II single arm EF-23 STELLAR trial. To account for the need of physicians and policymakers to objectively and comparably capture the clinical value of new cancer treatments the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have both developed assessment frameworks. We quantified the clinical value of the TTFields treatment in MPM by applying ASCO and ESMO frameworks to the comparison of the STELLAR data to historical controls. Materials/Methods: The EF-23 STELLAR Trial (n=80) demonstrated that adding TTFields to pemetrexed and cisplatin or carboplatin for malignant pleural mesothelioma patients resulted in overall survival of 18.2 months (95% CI 12.1-25.8) and progression free survival of 7.6 months (95% CI 6.7-8.6). The ESMO Magnitude of Clinical Benefit Scale (MCBS) and the ASCO Net Health Benefit (NHB) frameworks were applied to the EF-23 trial data using a historical control as comparator. Results: The application of the ASCO framework to the EF-23 data resulted in a NHB score of 52. This result was at the higher end of the score range of novel cancer treatments and compares well to the results for nivolumab in advanced non-squamous NSCLC and advanced squamous NSCLC as reference points. Applying the ESMO framework resulted in MCBS scores of A/5 (adjuvant/advanced) which would be the first score reported for MPM. The MCBS scores of A/5 are the highest scores achievable in the ESMO framework, and higher then the ESMO MCBS scores reported in the literature for NSCLC treatments. Conclusions: Despite differences in their respective concepts, both the ASCO and ESMO frameworks suggest that adding TTFields to Pemetrexed and Cisplatin or Carboplatin in malignant pleural mesothelioma patients may provide a significant clinical benefit. The high scores underline the fact that treatment with TTFields may extended progression free and overall survival without additional systemic toxicities. Citation Format: Justin Kelly, Uri Weinberg, Christina Proescholdt. Application of the ASCO and ESMO frameworks to TTFields treatment of mesothelioma [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 LB-161.

Radiological response patterns in the phase 2 STELLAR trial of TTFields with chemotherapy for first-line treatment of malignant pleural mesothelioma (MPM).

8551 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. TTFields have significantly extended survival of patients with glioblastoma. In-vitro, human MPM cells were highly susceptible to TTFields. In the STELLAR study, patients with unresectable MPM treated with first line chemotherapy in combination with TTFields had a significantly higher median overall survival compared to historical controls (18.2 vs. 12.1 months). We report on analysis of radiological data from STELLAR patients whose tumors responded while receiving the combined therapy. Methods: The STELLAR trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (&gt;18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria included ECOG PS of 0-1, pathologically proven mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients were followed q3w (CT scan q6w) until disease progression. Radiological assessments were done at each study site. Results: Partial responses (PRs) were seen in 40.3% of evaluable patients and clinical benefit (PR+SD) was seen in 97.2% of these patients. The median time between treatment start and PR was 1.8 months (range: 1.4-4.4 months). All patients presenting with PR during the STELLAR study had continuous reduction in the total sum of lesion diameters, suggesting no initial / pseudo-progression. 83% of the patients who responded to the combined therapy finally had disease progression within a median response duration of 5.7 months (range: 1.4-13 months), per Kaplan-Meier Estimator. One patient did not progress for more than 27 months. Conclusions: The STELLAR study met its primary endpoint of significant survival extension for previously untreated mesothelioma patients. Response rates were similar to the ones reported for the current standard of care treatment, but lasted longer with the addition of TTFields. Clinical trial information: NCT02397928.

The STELLAR trial protocol: a prospective multicentre trial for Richter\u2019s syndrome consisting of a randomised trial investigation CHOP-R with or without acalabrutinib for newly diagnosed RS and a single-arm platform study for evaluation of novel agents in relapsed disease

BackgroundTransformation of chronic lymphocytic leukaemia (CLL) to diffuse large B-cell lymphoma (DLCBL) type Richter’s syndrome (RS) carries a dismal prognosis. Standard-of-care chemoimmunotherapy for de novo RS is inadequate with median survival of less than one year. Patients are frequently elderly or have co-morbidities limiting dose-intense chemotherapy. Treatment of relapsed/refractory (R/R) RS and RS emerging after CLL-directed therapy represent urgent unmet clinical needs.Agents targeting Bruton’s tyrosine kinase (BTK) deliver improved outcomes for patients with high-risk CLL and expand effective treatments to frailer patients. Acalabrutinib is an oral, second-generation BTK inhibitor with a favourable toxicity profile and demonstrated activity in CLL and B-cell lymphomas. Combination of acalabrutinib with standard-of-care CHOP-R chemoimmunotherapy offers a sound rationale to test in a prospective trial for de novo RS.MethodsThe prospective multicentre STELLAR study is designed in two elements, consisting of a randomised study to evaluate the safety and activity of CHOP-R chemoimmunotherapy in combination with acalabrutinib in newly diagnosed RS and single-arm studies of novel agents for other RS patient cohorts.Eligible patients with newly diagnosed DLBCL-type RS are randomised between six cycles of CHOP-R therapy and six cycles CHOP-R plus acalabrutinib, followed by acalabrutinib maintenance. The primary endpoint of the randomised component is progression free survival (PFS).Cohort 1 enrols RS patients with progressive disease following chemoimmunotherapy for acalabrutinib monotherapy. Patients with RS diagnosed while on ibrutinib may enrol in Cohort 2, a single-arm study of CHOP-R plus acalabrutinib. The primary endpoint for the single-arm studies is overall response rate (ORR).Secondary endpoints for all cohorts are overall survival (OS), quality of life and proportion of patients proceeding to stem cell transplantation.The study will be accompanied by exploratory analysis of the mutational landscape of RS and the relationship between dynamic changes in sequential circulating tumour DNA samples and clinical outcomes.DiscussionThe STELLAR randomised trial evaluates the role of CHOP-R plus acalabrutinib in newly diagnosed RS patients. The single-arm platform studies enable the incorporation of promising novel therapies into the protocol. The STELLAR study has potential to identify novel biomarkers of treatment response in this high-risk malignancy.Trial registrationEudraCT: 2017–004401-40, registered on the 31-Oct-2017.IRSCTN: https://www.isrctn.com/ISRCTN52839057, registered on the 04-Mar-2019.ClinicalTrials.gov: NCT03899337, registered on 02-April-2019.

Tumor Treating Fields plus chemotherapy for first-line treatment of malignant pleural mesothelioma: Final Results of the STELLAR Trial

Tumor Treating Fields plus chemotherapy for first-line treatment of malignant pleural mesothelioma: Final Results of the STELLAR Trial

SAT-273-Impact of age on routinely available non-invasive tests for the discrimination of advanced fibrosis due to NASH in the phase 3 STELLAR trials of the ASK1 inhibitor selonsertib

SAT-273-Impact of age on routinely available non-invasive tests for the discrimination of advanced fibrosis due to NASH in the phase 3 STELLAR trials of the ASK1 inhibitor selonsertib

Reduced Patient-Reported Outcome Scores Associate With Level of Fibrosis in Patients With Nonalcoholic Steatohepatitis

Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis. We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI:SHP) before treatment initiation. Compared with patients with F3 fibrosis, higher proportions of patients with F4 fibrosis were female, were white, had more hematologic and gastrointestinal comorbidities, and had type 2 diabetes (P ≤ .01). Mean physical health-related PRO scores were significantly lower than thoseof the general population: patients with F4 fibrosis had score reductions of 4.4% to 12.9%in 6/8 SF-36 domains and patients with F3 fibrosis had score reductions of 3.9% to 11.7% in 4/8 domains (P < .01). Compared to patients with F3 fibrosis, those with F4 fibrosis had lower scores in all but 1 domains of CLDQ-NASH, Role Physical, Bodily Pain, and Social Functioning domains of the SF-36, and EQ-5D (P ≤ 01). In multivariate regression analysis, factors independently associated with lower PRO scores included having cirrhosis, female sex, higher body mass index, history of smoking, and diabetes or other comorbidities (P < .01). PROs are significantly lower in patients with NASH with advanced fibrosis who participated in the STELLAR clinical trials. Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life.

The Updated Results for the Phase 3 Study of 5×5 Gy Followed By Chemotherapy in Locally Advanced Rectal Cancer (STELLAR trial)

To present updated outcomes for the phase III trial comparing short-course radiotherapy (SCRT) followed by chemotherapy with long-course chemoradiotherapy (LCRT) in locally advanced rectal cancer (LARC). Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinomas staged by MRI, were randomized to either experimental or control group. The experimental group included SCRT (25 Gy/ 5 fractions/ 5 days) followed by 4 courses of CAPOX before surgery, and the control group consisted of preoperative LCRT (50Gy/ 25 fractions/35 days with concurrent capecitabine). Radical resection under TME principles was performed 6-8 weeks after neoadjuvant treatment, then 2 or 6 courses of CAPOX was prescribed as the postoperative adjuvant chemotherapy in experimental or control group, respectively. This is an ongoing trial, of which the initial results had been reported in ASTRO annual meeting 2016, and now this abstract is about updated data and experience. From August 30, 2015 to February 7, 2017, 238 eligible patients from 12 Chinese hospitals were enrolled, and no significant difference could be detected as to age, gender, TN staging, or MRF status between two groups. 170 patients had finished neoadjuvant treatment, of which grade 3+ acute toxicity was observed 20% of patients in experimental group and 4.7% in control group (p=0.002). In experimental group, the incidences of grade 3+ acute toxicity during 5×5 Gy, from end of SCRT to chemotherapy, and during chemotherapy were 0%, 7.1% and 14.1%, respectively. The most common grade 3+ acute toxicities included diarrhea (4.1%), asthenia (2.9%), and anemia (1.2%), most of which were reversible; but one patient in control group died from myocardial infarction. As a whole, full-dose completion of planned neoadjuvant treatment were observed 89.4% and 94.1% of patients in experimental and control group (p=0.493), respectively. For 115 patients who had undergone surgery, R0 resection rates and pCR rates in experimental and control group were 94.9% vs. 83.9% (p=0.054) and 18.6% vs. 5.4% (p=0.029), respectively, and the incidences of surgical complications were similar between two groups (experimental 30.5% vs. control 26.8%; p=0.659), with perineal complications as the majority of them. In addition, there were 10 patients diagnosed as clinical complete response (cCR) after SCRT followed by chemotherapy and they refused to further radical surgery, which contributing to 30.4% of overall CR rate (Including pCR and cCR) in experimental group. The mean time from surgery to the beginning of adjuvant chemotherapy was 54 days (range 28-91 days) in experimental group, which was longer than 43 days (range 23-97 days) in control group, p=0.05. The updated results supported proceeding of STELLAR trial based on acceptable acute toxicity and surgical complications, and high CR rate in patients with SCRT followed by chemotherapy was stable with increasing cases.(ClinicalTrails No. NCT02533271)

Abstract 4528: A novel transducer array design optimizing TTFields delivery to the thorax

Abstract Objective: The purpose of this study was to design transducer arrays for the delivery of Tumor Treating Fields (TTFields) to the thorax, generating high intensity in the upper torso while potentially improving patient comfort. Background: TTFields are low intensity, intermediate frequency, alternating electrical fields that disrupt cell division. The ongoing Phase II STELLAR trial [NCT02397928] is investigating the efficacy and safety of TTFields in combination with chemotherapy for the treatment of mesothelioma. A pivotal study to evaluate the efficacy of TTFields in treating NSCLC is planned for 2017. TTFields are delivered via capacitive transducer arrays, comprising ceramic disks covered with a thin layer of conductive medical-grade gel, which are arranged in an almost rectangular order. Two orthogonal pairs of arrays are placed on the skin in the vicinity of the treated region. One pair is placed on the anterior and posterior sides of the thorax. The other pair is placed on the lateral and contralateral sides of the thorax. This configuration has limitations: (a) Sub-optimal electric contact may be caused by poor attachment of the arrays on the chest due to body curvature; (b) TTFields intensity generated by anterior-posterior arrays may be attenuated in the thorax of females and obese individuals, due to high resistivity of the thick adipose layers in the breast; (c) the current lateral-contralateral arrays generate lower field intensities in the lung’s apex. This study presents novel array designs to overcome these limitations. Methods: Various concepts for array designs that avoid placement over regions of thick sub-cutaneous fat were designed. To evaluate the field distribution generated by these arrays and optimize their design, numerical simulations using realistic computational phantoms were used. Results: Novel array designs were developed for the delivery of TTFields to the lungs. These arrays consist of sets of interconnected small patches that adhere to the natural contours of the human body. Simulations showed that the proposed arrays deliver uniformly distributed, high electrical field to the lungs. One notable design is a pair of arrays shaped as circular rings, in which one array is placed around the neck and shoulders, whereas the second array is placed on the lower torso. This design yielded a highly uniform field directed longitudinally throughout the torso. Conclusion: The array designs presented in this study are expected to maintain patient comfort and will ensure high field intensity delivered to the thorax. Compliance and TTFields treatment delivery could both be improved by using these designs. Citation Format: Hadas S. Hershkovich, Sholi Strauss, Uri Weinberg, Eilon D. Kirson, Ze'ev Bomzon. A novel transducer array design optimizing TTFields delivery to the thorax [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4528. doi:10.1158/1538-7445.AM2017-4528

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

ContextThe present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians.Evidence AcquisitionPubMed searches were conducted using the keywords ‘statin, effect, and lipid profile’ from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles.ResultsCURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group.ConclusionsThe effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

The Initial Results for a Phase 3 Study of Short-Term Versus Long-Term Chemoradiation Therapy in Locally Advanced Rectal Cancer (STELLAR Trial)

The Initial Results for a Phase 3 Study of Short-Term Versus Long-Term Chemoradiation Therapy in Locally Advanced Rectal Cancer (STELLAR Trial)

The initial results for a phase III study of short-term radiotherapy plus chemotherapy vs long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR trial).

e15000Background: To present an initial results of a phase III trial of Short Term radiotherapy (SCRT) followed by chEmotherapy (experimental group) versus Long-term chemoradiotherapy (CRT) (contro...

AB0366 Pleiotropic Effects of Statins in the Treatment of Inflammatory Joint Diseases

BackgroundA lot of clinical studies have shown the beneficial pleiotropic effects of statins: both associated with reduction of cardiovascular risk, and response to the locomotory system such as their effects...

Comparing the effectiveness of rosuvastatin and atorvastatin in preventing cardiovascular outcomes: estimates using the Archimedes model

Objective:This study used simulation to compare the effectiveness of rosuvastatin 20 mg vs atorvastatin 40 mg, and rosuvastatin 40 mg vs atorvastatin 80 mg in preventing MACE in a range of patient populations with varying baseline cardiovascular risk.Research design and methods:The Archimedes Model was used to simulate head-to-head clinical trials in nine patient populations: Framingham Risk Score (FRS) ≥ 5%, 5–10%, 10–20%, > 20%, EURO-SCORE ≥ 5% and >10%, diagnosed diabetes, secondary prevention (history of myocardial infarction or stroke, CVD), and acute coronary syndrome (ACS). Simulated patients, aged 45–70 at trial start, were based on the NHANES 1999–2006. Treatments were modeled using results from the STELLAR, JUPITER, CARDS, ASCOT-LLA, and TNT trials. Treatment models were confirmed using trial validations.Results:Comparing rosuvastatin 20 mg vs atorvastatin 40 mg, the 5-year numbers needed to treat to prevent one MACE event (NNT) were 525, 70, and 55 for the FRS ≥ 5%, CVD, and ACS groups, respectively. Comparing rosuvastatin 40 mg vs atorvastatin 80 mg the corresponding NNT values were 468, 63, and 51. The 20-year relative risks of MACE in the FRS ≥ 5% population were 0.907 (0.901–0.913) for rosuvastatin 20 mg vs atorvastatin 40 mg and 0.892 (0.884–0.901) for rosuvastatin 40 mg vs atorvastatin 80 mg. The relative risks were similar for the remaining populations.Conclusions:This study found that rosuvastatin 20 mg and 40 mg lowers the risk of MACE more than atorvastatin 40 mg and atorvastatin 80 mg. While simulation models cannot replace real-world clinical trials, this study bridges gaps in the evidence, and identifies high risk cohorts that would likely see additional benefit from treatment with rosuvastatin rather than atorvastatin.

Abstract 243: Comparing the Major Adverse Cardiovascular Event Risk of Treatment and Titration Sequences Using Atorvastatin and Rosuvastatin: a Simulated Study

Objective: Using simulation modeling, we compared the effects of initiating statin therapy with atorvastatin and rosuvastatin on a population of patients with LDL-C levels above goal. Methods: Using the Archimedes Model, a clinically detailed simulation model of human physiology, disease progression, and healthcare delivery, two treatment scenarios were simulated in which patients initiated atorvastatin (10, 20, 40, or 80 mg) or rosuvastatin (10, 20, or 40 mg), and then periodically intensified treatment at rates determined from US pharmacy claims. Simulated individuals (derived from NHANES 1999-2006) were aged 45 to 70 years and had LDL-C exceeding Adult Treatment Panel (ATP) III goal. Initial statin doses were conservatively assigned based on each individual's LDL-C, their LDL-C goal, and the expected treatment effect. Patients not reaching goal either intensified the current statin dose or switched to an appropriate rosuvastatin dose. Occurrence of major adverse cardiovascular event (MACE), comprising MI, stroke, or cardiovascular (CV) death, was tracked for 10 years for all patients and several high-risk subpopulations, including those with diagnosed diabetes and with prior CV disease (CVD). Statin effects were modeled using biomarker results from the STELLAR trial and outcomes data from the JUPITER trial (rosuvastatin) and the CARDS, ASCOT, and TNT trials (atorvastatin). Results: At baseline, the study population (n=50,025) had a mean age of 57.3 [SD: 6.9] years, were 56% male, and had average LDL-C of 166.6 [41.3] mg/dL, HDL-C 49.3 [13.7] mg/dL, total cholesterol 252.0 [50.2] mg/dL, BMI 30.2 [6.6] kg/m2, 26% had diagnosed diabetes, 58% had hypertension, and 25% were current smokers. Initiating treatment with rosuvastatin versus atorvastatin provided a significant reduction in MACE: the 5- and 10-year relative risk of MACE for the overall population was 0.92 (95% CI: 0.90[[Unsupported Character - &amp;#61485;]]0.94) and 0.92 (95% CI: 0.91-0.93), respectively; with prior diabetes, 0.90 (95% CI: 0.86[[Unsupported Character - &amp;#61485;]]0.94) and 0.91 (95% CI: 0.88-0.93); and with prior CVD, 0.93 (95% CI: 0.90[[Unsupported Character - &amp;#61485;]]0.97) and 0.95 (95% CI: 0.93-0.97); all p&lt;0.05. Conclusion: In this simulation model, initial treatment with rosuvastatin versus atorvastatin lowered the incidence of MACE across the overall study population and in patients with prior diabetes or CVD.