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Cancer-related internet use in patients with advanced cancer in a phase I clinical trials clinic
Poster Session – Clinical Trial Methodology, Wednesday 29 November 2016 refined somatic variant calling in comparison to tumor-only analysis. The assay also performed robustly in real clinical specimens, including FFPE. Further data will be presented summarizing the sensitivity and specificity results for the exome and transcriptome assay. Conclusions: We have developed and validated comprehensive cancer NGS assays, with highly uniform + deep coverage, ensuring high sensitivity and specificity for all variant types. This assay represents a versatile tool that can be used to (i) test a core set of clinically actionable genes, (ii) implicate new cancer genes as clinically relevant, (iii) facilitate discovery of novel therapeutic targets. Conflict of interest: Ownership: Financial relationships (such as employment, stock ownership or options, patents) may exist. 183 Poster (Board P009) Cancer-related internet use in patients with advanced cancer in a phase I clinical trials clinic G. George1 , A. Buford2 , K. Hess3 , S. Piha-Paul2 , R. Zinner2 , V. Subbiah2 , E. Iwuanyanwu2 , C. Cleeland4 , F. Meric-Bernstam2 , E. Bernstam5 , D. Hong2 . 1 MD Anderson Cancer Center, Investigational Cancer Therapeutics, Symptom Research, Houston, TX, USA; 2 MD Anderson Cancer Center, Investigational Cancer Therapeutics, Houston, TX, USA; 3 MD Anderson Cancer Center, Biostatistics, Houston, TX, USA; 4 MD Anderson Cancer Center, Symptom Research, Houston, TX, USA; 5 The University of Texas Health Science Center at Houston, The University of Texas School of Biomedical Informatics, Houston, USA Background: We examined patterns, correlates and impact of cancerrelated internet use among patients with advanced cancer in a clinic for phase I clinical trials of molecularly targeted oncologic agents. Material and Methods: An anonymous questionnaire on internet use for cancer-related purposes, incorporating input from phase I physician oncologists and clinical trial clinic patients, was self-administered by patients (age 18 y) in a phase I clinic for targeted therapy. Multivariable modeling was used. Data were analyzed for the overall sample and by generation, defined by year of birth as follows: Millennials (after 1990), Generation X/Y (1965–1990), Baby Boomers (1946–1964), and Greatest/Silent Generation (1945 and prior). Results: Of 291 patients (52% women, 82% non-Hispanic white, 50% 60 years) seen in a phase I clinic beginning in 2012, 62% were cancerrelated internet users (CIUs). Cancer-related internet use was associated with an income of >$60,000 (OR = 2.42, p = 0.004). CIUs used the internet more to learn about cancer, drugs, and treatment/clinical trials rather than for emotional support. The hospital website (70% of CIUs) was most frequently used to learn about clinical trials, followed by ClinicalTrials.gov (42%), and search engines (41%). CIUs reported informational gains from the internet about their cancer (85%), side effects of treatment (65%), clinical trials (52%), new alternative treatments for their cancer (42%), and management of symptoms (41%). Emotional impact of internet-derived cancer information on CIUs varied: 56% felt empowered, 34% anxious, 29% relieved, and 17% confused. Cancer-related internet information made 51% of Millennials/Generation X/Y CIUs anxious compared to <29% of CIUs from older generations (born 1964 and prior). Most CIUs desired more online information about new experimental drugs (91%) and US Food and Drug Administration-approved drugs for cancer (72%). Based on mean scores of trust measured on six-point likert scales ranging from 0 (no trust) to 5 (complete trust), trust of online cancer-related information was higher among CIUs than among non-CIUs (2.8 vs. 1.8, p < 0.001). However, CIUs and non-CIUs did not differ in their trust of referring (4.4 vs. 4.5, p > 0.05) or phase I physicians (4.3 vs. 4.2, p > 0.05). CIUs’ trust of referring (4.4) and phase 1 physicians (4.3) were higher than CIUs’ trust of online cancerrelated information (2.8) (p < 0.001 for both). Conclusions: As most phase I patients use the internet for cancerrelated purposes, the internet should be leveraged to provide accurate and empowering information to phase I patients. Websites of hospitals that conduct early-phase trials should be updated with the latest clinical trialrelated information for patients. Given phase 1 patients’ trust of physicians, physician-authored or attributed content should be prioritized on hospital websites. No conflict of interest. 184 Poster (Board P010) A robust population-based screening platform, HuScreen™, enables identification of candidates, indications and biomarkers by mouse clinical trial using a large, diverse and fully annotated PDXs S. Guo1 , D. Ouyan1 , D. Chen1 , X. Huang1 , H. Li1 . 1 Crown Bioscience, Translational Oncology, Santa Clara, USA Background: While patient derived xenograft (PDX) mimics original patient, a large cohort of PDXs reflect heterogeneity of patient pop-
Poster abstracts
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ulations [1,2], which enables drug efficacy evaluation in a populationbased clinical trial (HuTrial™) to select indication and guide patient stratification [3−5]. Recent works by others have also demonstrated the utility of this type of trial format for screening large panel of candidate agents, enabling prioritization of lead development [6] and reposition of existing drugs. Method: We aim at building a large diverse PDX library and large-scale global industry capacity supporting multiple-center mouse clinical trial (MCT). We analyzed several MCT datasets to assess the impact of different parameters used in trial/screen process, including endpoints, number of models, number of mice per treatment group, etc., which can be further used to guide the trial/screen design and data analysis, so the final data can adequately support conclusions and answer important translational questions. Results: We have built the largest diverse PDX library (>3,000 HuPrime® ) with full annotations (1, 3−5, 7−9) that enables the simultaneous testing of large panel of different agents on hundreds of subject models. A large cohort of live models (hundreds, also called warm test subjects) maintained in our facilities enable speedy trial enrollment and ensure rapid MCT. Piggyback strategy at the global scale with many partners can significantly reduce trial cost and broaden the acceptance. We have generated several MCT datasets, from which we compared the common response or survival endpoints used in human (RECIST, OS, PFS) and mice (DT /DC , TGI, PFS, OS), and established certain levels of relevance/equivalency. We then discussed suitable situations for each endpoint can be used. We have assessed scenarios of using different number of mice per group and/or different number of models in MCT and provided estimates on required number of models/mice based on the questions asked. We also explored novel data analysis methods beyond traditional endpoint analysis, and identified new methods sufficiently robust to handle the high variations in tumor growth dynamics in different mice or models during MCT. We also developed new statistic approaches to discover predictive biomarkers (signatures) according to trial data and model annotations. Conclusion: Optimally designed and implemented HuScreen™ platform can be a powerful tool to prioritize candidates, select indications and discover predictive biomarkers, as well as repurpose drugs. No conflict of interest. 185 Poster (Board P011) Suitability of post-diagnostic core needle tumor biopsies for correlative studies of molecular drug action (pharmacodynamics) K. Ferry-Galow1 , H. Makhlouf2 , R. Kinders1 , A. Chen3 , J.H. Doroshow3 , R. Parchment1 . 1 Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Directorate, Frederick, MD, USA; 2 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Cancer Diagnosis Program, Rockville, MD, USA; 3 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Early Clinical Trials Development Program, Bethesda, MD, USA Background: Although key specimens for evaluating tumor pharmacodynamic (PD) response using biomarkers of molecular drug action, core needle biopsies collected during Phase 0/1 clinical trials from various metastatic lesions and histological origins present with high heterogeneity and variable tumor content. We have found that a significant percentage of biopsies are unsuitable for PD evaluation across multiple assay platforms, and new approaches, sampling methods and procedures are needed to improve the percentage of evaluable biopsies. Materials and Methods: For microscopy-based measurements, biopsy pairs are collected using image guidance are snap-frozen, thawed under fixative, and embedded in parallel. The likelihood of finding optimal regions for biomarker analyses is optimized by preparing a series of 35 sections; flanking slides are stained with H&E and annotated by an anatomic pathologist who determines whether tumor content is sufficient to meet assay requirements. Results: From evaluating 87 biopsies for slide based PD analyses across three trials at NCI’s Developmental Therapeutics Clinic (DTC), 65% of biopsies and 53% of biopsy pairs were found to contain sufficient tumor content to be suitable for the intended quantitative immunofluorescence assay (qIFA). Approximately 18% contained tumor content too low to adequately represent the tumor as a whole given the biomarker variability and/or to yield a reliable quantitative measurement using current procedures. Additionally, 16% were found to contain no analyzable tumor cells. Similar incidences of both low- and no-tumor content biopsies have been observed at several other clinical centers. Conclusions: There are different requirements of tumor sampling for diagnosis and for studies of drug mechanism. Improved communication between oncologists and radiologists will provide better understanding of factors that affect the suitability of biopsies for robust PD biomarker analyses. NCI’s DTC has implemented protocol modifications including
Poster abstracts
S65
ulations [1,2], which enables drug efficacy evaluation in a populationbased clinical trial (HuTrial™) to select indication and guide patient stratification [3−5]. Recent works by others have also demonstrated the utility of this type of trial format for screening large panel of candidate agents, enabling prioritization of lead development [6] and reposition of existing drugs. Method: We aim at building a large diverse PDX library and large-scale global industry capacity supporting multiple-center mouse clinical trial (MCT). We analyzed several MCT datasets to assess the impact of different parameters used in trial/screen process, including endpoints, number of models, number of mice per treatment group, etc., which can be further used to guide the trial/screen design and data analysis, so the final data can adequately support conclusions and answer important translational questions. Results: We have built the largest diverse PDX library (>3,000 HuPrime® ) with full annotations (1, 3−5, 7−9) that enables the simultaneous testing of large panel of different agents on hundreds of subject models. A large cohort of live models (hundreds, also called warm test subjects) maintained in our facilities enable speedy trial enrollment and ensure rapid MCT. Piggyback strategy at the global scale with many partners can significantly reduce trial cost and broaden the acceptance. We have generated several MCT datasets, from which we compared the common response or survival endpoints used in human (RECIST, OS, PFS) and mice (DT /DC , TGI, PFS, OS), and established certain levels of relevance/equivalency. We then discussed suitable situations for each endpoint can be used. We have assessed scenarios of using different number of mice per group and/or different number of models in MCT and provided estimates on required number of models/mice based on the questions asked. We also explored novel data analysis methods beyond traditional endpoint analysis, and identified new methods sufficiently robust to handle the high variations in tumor growth dynamics in different mice or models during MCT. We also developed new statistic approaches to discover predictive biomarkers (signatures) according to trial data and model annotations. Conclusion: Optimally designed and implemented HuScreen™ platform can be a powerful tool to prioritize candidates, select indications and discover predictive biomarkers, as well as repurpose drugs. No conflict of interest. 185 Poster (Board P011) Suitability of post-diagnostic core needle tumor biopsies for correlative studies of molecular drug action (pharmacodynamics) K. Ferry-Galow1 , H. Makhlouf2 , R. Kinders1 , A. Chen3 , J.H. Doroshow3 , R. Parchment1 . 1 Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Directorate, Frederick, MD, USA; 2 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Cancer Diagnosis Program, Rockville, MD, USA; 3 Division of Cancer Treatment and Diagnosis, National Cancer Institute, Early Clinical Trials Development Program, Bethesda, MD, USA Background: Although key specimens for evaluating tumor pharmacodynamic (PD) response using biomarkers of molecular drug action, core needle biopsies collected during Phase 0/1 clinical trials from various metastatic lesions and histological origins present with high heterogeneity and variable tumor content. We have found that a significant percentage of biopsies are unsuitable for PD evaluation across multiple assay platforms, and new approaches, sampling methods and procedures are needed to improve the percentage of evaluable biopsies. Materials and Methods: For microscopy-based measurements, biopsy pairs are collected using image guidance are snap-frozen, thawed under fixative, and embedded in parallel. The likelihood of finding optimal regions for biomarker analyses is optimized by preparing a series of 35 sections; flanking slides are stained with H&E and annotated by an anatomic pathologist who determines whether tumor content is sufficient to meet assay requirements. Results: From evaluating 87 biopsies for slide based PD analyses across three trials at NCI’s Developmental Therapeutics Clinic (DTC), 65% of biopsies and 53% of biopsy pairs were found to contain sufficient tumor content to be suitable for the intended quantitative immunofluorescence assay (qIFA). Approximately 18% contained tumor content too low to adequately represent the tumor as a whole given the biomarker variability and/or to yield a reliable quantitative measurement using current procedures. Additionally, 16% were found to contain no analyzable tumor cells. Similar incidences of both low- and no-tumor content biopsies have been observed at several other clinical centers. Conclusions: There are different requirements of tumor sampling for diagnosis and for studies of drug mechanism. Improved communication between oncologists and radiologists will provide better understanding of factors that affect the suitability of biopsies for robust PD biomarker analyses. NCI’s DTC has implemented protocol modifications including