Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (pts) with advanced non-colorectal (non-CRC) gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3516-3516
Author(s):  
Akihiro Ohba ◽  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Masafumi Ikeda ◽  
Hideaki Bando ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Cancer Type ◽  
Combined Analysis ◽  
Clinical Sequencing ◽  
Upper Gi ◽  
Gi Cancer ◽  
Wide Range ◽  
Gi Cancers

3516 Background: We recently reported that clinical assessment of genomic biomarkers using ctDNA had advantages over tumor tissue-based sequencing for enrollment into matched clinical trials across a wide range of GI cancers. Herein we investigated the utility of ctDNA in non-CRC cancers in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue samples of pts with non-CRC were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay, since Feb 2015. In GOZILA, plasma samples of non-CRC pts were analyzed by an NGS-based ctDNA assay, Guardant360, since Feb 2018. Results: As of Apr 2019, 2,952 pts in GI-SCREEN and 633 pts in GOZILA were enrolled. Baseline characteristics between the groups were well matched except that GOZILA included more pancreatic (P < 0.0001) and liver cancers (P = 0.016) but fewer gastric cancers (P < 0.0001) and GIST (P = 0.020) than GI-SCREEN. The success rates of the tests were 86.6% in GI-SCREEN and 87.3% in GOZILA (P = 0.649). Median turnaround time (TAT) was 37 days in GI-SCREEN and 12 days in GOZILA (P < 0.0001). The proportion of cases with actionable alterations detected (tissue vs blood; 29.8% vs 46.8%, P < 0.0001) and enrolled into matched clinical trials (4.8% vs 6.5%, P = 0.286) for each group by cancer type are shown in the Table. Pts with upper GI cancers, especially those in GOZILA, were more often enrolled into matched trials; trial enrollment for those with hepatobiliary and pancreatic (HBP) or other cancers was similar regardless of testing method. Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.0 and 1.0 months (mo), respectively (P < 0.0001). Objective response rates (ORR) and progression-free survival (PFS) were not significantly different (tissue vs. blood; ORR: 14.6 vs. 26.3%, P = 0.30: median PFS: 3.3 vs. 2.6 mo, P = 0.71). Conclusions: Clinical sequencing of ctDNA, with its shorter TAT, contributed to rapid enrollment of non-CRC pts into matched clinical trials compared to those tested by tumor tissue sequencing, particularly for those with upper GI cancer, without compromising efficacy. Clinical trial information: UMIN000029315 . [Table: see text]

Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (Pts) with advanced gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Hideaki Bando ◽  
Ken Kato ◽  
Taito Esaki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Objective Response ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Tissue Samples ◽  
Combined Analysis ◽  
Clinical Sequencing ◽  
Gi Cancer

5 Background: Blood-based genomic profiling by ctDNA analysis has a promise to potentially identify actionable genomic alterations. However, utility of clinical sequencing with ctDNA compared with that with tumor tissue for enrolling cancer pts to matched clinical trials remains unclear. Herein we investigated the utility of ctDNA clinical sequencing by the SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis. Methods: In the GI-SCREEN, tumor tissue samples of pts with advanced GI cancer were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In the GOZILA, plasma samples of pts with advanced GI cancer were analyzed by an NGS-based ctDNA assay, Guardant360 since Feb 2018. Tests were performed centrally by CLIA-certified and CAP-accredited laboratories. Pts with actionable alterations were enrolled to matched company-sponsored or investigator-initiated clinical trials. Results: As of Apr 2019, test results were generated in 5,029 out of 5,743 pts (88%) in GI-SCREEN and 1,089 out of 1,103 pts (99%) in GOZILA ( P < 0.0001).Median turnaround time (TAT) was 35 days in GI-SCREEN and 12 days in GOZILA ( P < 0.0001). There were no differences in other baseline characteristics between GI-SCREEN and GOZILA. Proportion of enrolling matched clinical trials in GOZILA was significantly higher than that in GI-SCREEN (126 pts [2.2%] in GI-SCREEN vs. 60 pts [5.4%] in GOZILA, P < 0.0001). Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.9 and 1.0 months (mo), respectively ( P < 0.0001). The objective response rate (ORR) and progression-free survival (PFS) were not significantly different (ORR: 17.5 vs. 16.7%, P = 1.00; median PFS: 2.8 vs. 2.0 mo, P = 0.24). Conclusions: Clinical sequencing with ctDNA having the advantage of the shorter TAT enrolled more pts with advanced GI cancer to matched clinical trials than those with tumor tissue, without compromising the efficacy. Clinical trial information: UMIN000029315.

Utility of circulating tumor DNA (ctDNA) versus tumor tissue genotyping for enrollment of patients with metastatic colorectal cancer (mCRC) to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4071-4071
Author(s):  
Yoshiaki Nakamura ◽  
Hiroya Taniguchi ◽  
Hideaki Bando ◽  
Taito Esaki ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Objective Response ◽  
Progression Free Survival ◽  
Turnaround Time ◽  
Circulating Tumor Dna ◽  
Combined Analysis ◽  
Wide Range

4071 Background: We recently reported that ctDNA genotyping had advantages compared with tumor tissue testing in terms of enrollment to matched clinical trials across a wide range of GI cancers (Nakamura Y, et al. ASCO-GI 2020). Here, we investigated the utility of ctDNA genotyping in mCRC in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue genotyping was performed using a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In GOZILA, NGS-based ctDNA genotyping was performed using Guardant360 since Feb 2018. All tests were conducted centrally in a CLIA-certified and CAP-accredited laboratory. Patients with actionable alterations were enrolled into matched company-sponsored or investigator-initiated interventional clinical trials. Results: As of Apr 2019, 2,791 mCRC patients (2,754 eligible for analysis) in GI-SCREEN and 470 (464 eligible for analysis) in GOZILA were enrolled. There were no significant differences in baseline patient characteristics between GI-SCREEN and GOZILA. Most of trials affiliated with GI-SCREEN (81%) or GOZILA (78%) targeted the RTK/RAS/RAF pathway. Compared with tumor testing, ctDNA genotyping significantly improved turnaround time (median, 12 vs. 34 days, P < 0.0001), sequencing success rate (96.1 vs. 92.3%, P = 0.002), and detection rate of actionable alterations (73.3 vs. 62.2%, P = 0.02). Among patients with actionable alterations, enrollment to matched clinical trials was achieved in 5.0% in GI-SCREEN and 12.1% in GOZILA ( P < 0.0001). Median time from enrollment in the respective screening study to enrollment in a matched clinical trial was 6.5 months in GI-SCREEN and 0.9 months in GOZILA, respectively ( P < 0.0001). Objective response rate and progression-free survival were similar in both groups (tissue vs. ctDNA; ORR: 18.8 vs. 17.1%, P = 1.00; median PFS: 2.2 vs. 2.2 months, HR=1.05 [95% CI, 0.71–1.55], P = 0.79). Conclusions: For patients with mCRC, ctDNA genotyping had advantages over tissue genotyping with shorter turnaround time and higher sequencing success and actionable alteration detection rate, which were associated with improved clinical trial enrollment without compromising the efficacy. Funding: SCRUM-Japan Funds. Clinical trial information: UMIN000029315 .

Disparities in clinical trials participation in a vertically integrated care delivery system.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 128-128
Author(s):  
Ahmed Megahed ◽  
Gary L Buchschacher ◽  
Ngoc J. Ho ◽  
Reina Haque ◽  
Robert Michael Cooper
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Healthcare System ◽  
Care Delivery ◽  
Trial Participation ◽  
Cancer Type ◽  
Clinical Trial Participation ◽  
Integrated Healthcare ◽  
Clinical Trial Enrollment ◽  
Asian Pacific

128 Background: Sparse data exists on the diversity clinical trial enrollment in community settings. This information is important to ensure equity of care and generalizability of results. Methods: We conducted a retrospective cohort study of members of an integrated healthcare system diagnosed with invasive malignancies (excluding non-melanoma skin cancers) between 2013-2017 to examine demographics of the oncology population compared to those who enrolled in a clinical trial. Logistic regression was used to assess correlates of clinical trial participation, comparing general and screened samples to enrolled sample. Odds ratios were adjusted for gender, geocoded median household income, cancer type, and stage. Results: Of the 84,977 patients with a cancer diagnosis, N = 2606 were screened for clinical trial participation and consented, and of those N = 1372 enrolled. The percent of Latinx (25.8% vs 24.0%; OR 0.9? CI 0.72-1.05) and African American/Black (10.9% vs 11.1%; OR 0.92 CI 0.75-1.11) clinical trial participation mirrored that of the general oncology population, respectively using Non-Hispanic Whites as reference. Asian/Pacific Islander had equal odds of clinical trial enrollment (OR 1.08 CI 0.92-1.27). The enrolled population was younger than the general oncology population. Conclusions: This study suggests that in an integrated healthcare system with equal access to care, the clinical trials population is well representative of its general oncology population.[Table: see text]

Correlation of psychosocial factors (PSF) before and throughout treatment with response to chemotherapy (CTx) in patients (pts) with advanced gastrointestinal (GI) cancers: Does psychosocial status predict tumor remission?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 542-542
Author(s):  
Anna Maria Offergeld ◽  
Anna Drabik ◽  
Karin Oechsle ◽  
Anja Mehnert ◽  
Djordje Atanackovic ◽  
...  
Keyword(s):  
Predictive Value ◽  
Positive Impact ◽  
Symptom Assessment ◽  
Physical Symptoms ◽  
Cancer Type ◽  
Brief Cope ◽  
Gi Cancer ◽  
Response To Chemotherapy ◽  
Gi Cancers ◽  
Eortc Qlq

542 Background: CTx has shown to have a positive impact on improving or maintaining quality of life (QoL) in patients with advanced GI cancers. The role of PSF in relation to objective tumor response (OTR) to CTx is not well described yet. We thus evaluated the predictive value of pretreatment PSF on OTR as well as the continuous evaluation of PSF in regard to OTR throughout treatment. Methods: Eligible pts had metastatic or recurrent GI cancer and were about to receive first- and second-line palliative CTx. QoL, physical symptoms and PSF were assessed by the EORTC QLQ C30, the MSKCC-Symptom Assessment Scale (MSAS), and a modified Brief-COPE before treatment start and after discussing the results of the first follow up OTR assessment. OTR was either classified according to RECIST or using a remission based approach (RA), classifying response as any decrease in size, and no change or progression as non-response. Results: 50 pts (median age 61.8 years, ECOG 0/1/2 12%/62%/26%, 21 female, 40% colorectal, 28% biliopancreatic, 24% esophagogastric, 78% 1st line CTx) were enrolled. OTR was 32% partial response, 50% stable disease and 18% progressive disease according to RECIST, and 60% response vs. 40% non-response according to RA. Interestingly, patients responding (RECIST and RA) to CTx had better role/emotional/cognitive functioning, mental state, global distress index, active coping, positive reframing, and belief in control over their lives, and less acceptance of their disease before treatment. PSF significantly predicted response (RA) to CTx, even if adjusted for age, cancer type, and line of treatment (p<0.05). During course of treatment, PSF remained largely unchanged in responders, whereas non-responders loose belief and confidence in control, safety and equity and tend to increased denial (RECIST and RA). Those findings were more pronounced using the RA classification than RECIST. Conclusions: Pretreatment PSF seem to have predictive value for response to CTx in GI cancer patients. PSF changes in non-responding patients may be an early indicator for the need for psychological support in this patient group.

Risk factors for hospitalizations (HOS) among older adults with gastrointestinal (GI) cancers receiving chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Daneng Li ◽  
Can-Lan Sun ◽  
Abrahm Levi ◽  
Heidi D. Klepin ◽  
Rawad Elias ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Psychological State ◽  
Cancer Type ◽  
Gi Cancer ◽  
Increased Risk ◽  
Gi Cancers ◽  
Cardiac Comorbidity

e21523 Background: Older adults undergoing chemotherapy for GI cancers are at increased risk of HOS due to treatment related toxicity; however, there are limited data regarding which individuals are at greatest risk. We therefore sought to identify risk factors for HOS among older adults with GI cancers receiving chemotherapy. Methods: We performed a secondary analysis of patients age ≥ 65 years with GI cancer who participated in either of 2 prospective studies used to develop (n = 500) and validate (n = 250) a geriatric assessment (GA) based chemotherapy toxicity score for older adults with cancer. The incidence of HOS within 30 days post treatment was determined. The following patient characteristics were captured pre-chemotherapy: demographics, cancer type, stage, laboratory values, chemotherapy type, and GA measures (functional status, comorbidity, psychological state, cognitive function, nutritional status, and social support). Univariate and multivariate logistic regressions were used to estimate the odds ratio (OR) to identify risk factors. Results: A total of 199 adults age 65+ (median 73; range 65-94) with GI cancers (colorectal 43%, gastric/esophageal 25%, pancreas/biliary 32%; Stage I-III 42%, stage IV 58%) receiving chemotherapy (67% poly-chemotherapy) were included. 5-FU chemotherapy was administered alone or in combination in 126 (63%) patients. Sixty five (33%) patients had ≥1 HOS (1 HOS: 55, 2 HOS: 9, 3 HOS: 1). In univariate analysis, hospitalized patients were more likely to be female (p = 0.02), have stage IV disease (p = 0.03), have a diagnosis of non-colorectal GI cancer (p = 0.04), have poly-pharmacy (≥ 5 medications, p < 0.01), decreased hearing (p = 0.05), cardiac comorbidity (p < 0.01), and low serum albumin (p = 0.05). On multivariate analyses, patients who were female (OR = 2.06, 95% CI: 1.05-4.06), with cardiac comorbidity (OR = 3.73, 95% CI: 1.78-7.83), or a diagnosis of stage IV non-colorectal GI cancer (OR = 3.75, 95% CI: 1.50-9.39) were more likely to be hospitalized. Conclusions: HOS during chemotherapy treatment are common among older adults with GI cancers. Female sex, cardiac comorbidity, and a diagnosis of stage IV non-colorectal GI cancer are risk factors for HOS.

No-cost next generation sequencing of advanced cancer patients within the Strata Precision Oncology Network supports clinical trial enrollment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3073-3073
Author(s):  
Marc Ryan Matrana ◽  
Scott A. Tomlins ◽  
Kat Kwiatkowski ◽  
Khalis Mitchell ◽  
Jennifer Marie Suga ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Clinical Samples ◽  
Precision Oncology ◽  
Cancer Type ◽  
Next Generation ◽  
Match Trial ◽  
The Impact ◽  
Generation Sequencing

3073 Background: Widespread integration of systematized next generation sequencing (NGS)-based precision oncology is hindered by numerous barriers. Hence, we developed the Strata trial (NCT03061305), a screening protocol to determine the impact of scaled precision oncology. Methods: We implemented no-cost NGS on formalin fixed paraffin embedded (FFPE) clinical samples for all patients with advanced tumors, a common portfolio of partnered therapeutic clinical trials, and robust infrastructure development across the Strata Precision Oncology Network. Results: Across the network of 17 centers, specimens from 8673/9222 (94%) patients were successfully tested in the Strata CLIA/CAP/NCI-MATCH accredited laboratory using comprehensive amplicon-based DNA and RNA NGS. Patients were tested with one of three StrataNGS test versions; the most recent panel assesses all classes of actionable alterations (mutations, copy number alterations, gene fusions, microsatellite instability, tumor mutation burden and PD-L1 expression). Median surface area of received FFPE tumor samples was 25mm2 (interquartile range 9-95mm2), and the median turnaround time from sample receipt to report was 6 business days. 2577 (27.9%) patients had highly actionable alterations, defined as alterations associated with within-cancer type FDA approved or NCCN guideline recommended therapies (1072 patients), NCI-MATCH trial arms (1467 patients), Strata-partnered therapeutic trials (327 patients), or specific alteration-matched FDA approved therapies in patients with cancers of unknown primary (71 patients). Of the 1467 patients matched to an NCI-MATCH trial arm, 15 enrolled. Of the 327 patients matched to one of nine Strata-partnered clinical trials, 77 (24%) were screen failures, while 250 (76%) have either enrolled or are being actively followed for enrollment upon progression. Conclusions: Through streamlined consent methods, electronic medical record queries, and high throughput laboratory testing at no cost to patients, we demonstrate that scaled precision oncology is feasible across a diverse network of healthcare systems when paired with access to relevant clinical trials. Clinical trial information: NCT03061305.

scholarly journals Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

2021 ◽  
pp. 859-875
Author(s):  
Amanda O. L. Seet ◽  
Aaron C. Tan ◽  
Tira J. Tan ◽  
Matthew C. H. Ng ◽  
David W. M. Tai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Tissue ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Cancer Center ◽  
Precision Oncology ◽  
Molecular Tumor Board ◽  
Tumor Types ◽  
Tertiary Cancer Center

PURPOSE Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.

Global drug development in cancer: A cross-sectional study of clinical trial registries

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2520-2520
Author(s):  
P. Hertz ◽  
B. Seruga ◽  
L. W. Le ◽  
I. F. Tannock
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Development ◽  
Phase Ii ◽  
New Drugs ◽  
Phase Iii ◽  
Cancer Site ◽  
Cancer Type ◽  
Clinical Trial Registries ◽  
Global Drug Development

2520 Background: Clinical trials are increasingly funded by industry. High costs of drug development may lead to attempts to develop new drugs in more ‘profitable’ (i.e., more prevalent) as compared to ‘less profitable’ (i.e., more deadly) cancers. Here we determine the focus of current global drug development. Methods: We determined characteristics of phase II and III clinical trials evaluating new drugs in oncology, which were registered with WHO International Clinical Trial Registries between 01/2008 and 06/2008. Estimates of incidence, mortality, and prevalence in the more- and less-developed world (MDW, LDW) were obtained from GLOBOCAN 2002. Simple correlation analysis was performed between the number of clinical trials and incidence, mortality and prevalence per cancer site after log transformation of variables. Results: We identified 399 newly registered trials. Of 374 trials with information about recruitment, 322 (86.1%) and 39 (10.4%) recruited patients only from the MDW and LDW, respectively, while 13 (3.5%) had worldwide recruitment. 229 (58%) of trials were sponsored by industry and 324 trials were phase II (81%). Most trials (and most phase III trials) evaluated treatments for globally prevalent cancers: breast, lung, prostate, and colorectal cancer (Table). Prevalence of a particular cancer type in both the MDW and LDW correlated significantly with the number of clinical trials (Pearson r = 0.63 and 0.55; p = 0.01 and 0.03, respectively). In contrast, mortality in the MDW (Pearson r = 0.73; p= 0.002), but not in the LDW (Pearson r = 0.38; p= 0.17), correlated significantly with the number of clinical trials. Conclusions: Global drug development in cancer predominates in globally prevalent cancers, which are a more important cause of mortality in the MDW than in the LDW. Cancer sites that are major killers globally, and especially in the LDW (e.g., stomach, liver, and esophageal cancer) should receive priority for clinical research. [Table: see text] No significant financial relationships to disclose.

Algorithmic matching of genomic profiles to precision cancer medicine clinical trials at DFCI.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6620-6620
Author(s):  
James Lindsay ◽  
Catherine Del Vecchio Fitz ◽  
Zachary Zwiesler ◽  
Priti Kumari ◽  
Khanh Tu Do ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Open Source ◽  
Patient Specific ◽  
Cancer Type ◽  
Eligibility Criteria ◽  
Enrollment Rates ◽  
And Gender ◽  
Computational Platform

6620 Background: Genomic profiling and access to precision medicine clinical trials are now standard at leading cancer institutes and many community practices. Interpreting patient-specific genomic information and tracking the complex criteria for precision medicine trials requires specialized computational tools, especially for multi-institutional basket studies such as NCI-MATCH and TAPUR. Methods: To address this challenge we have developed an open source computational platform for patient-specific clinical trial matching at Dana-Farber Cancer Institute (DFCI) called MatchMiner, which aides in both patient recruitment to precision medicine trials, as well as decision support for oncologists. Trial matches are computed based on genomic criteria, including mutations, CNAs, and SVs, as well as clinical and demographic information, including cancer type, age, and gender. A formal standard called clinical trial markup language (CTML) to encode complex clinical trial eligibility criteria has also been created. Results: MatchMiner is now available at DFCI. Currently 123 precision medicine clinical trials have been transformed into CTML and 13,000 patient records are available, with over 88% of current patients having at least 1 match (average 2.6). A total of 103 genes are specified as criteria for at least 1 trial. KRAS, TP53, PTEN, PIK3CA and BRAF are the genes driving the most number of matches. General usage statistics and trial enrollment rates are currently being monitored to determine the system effectiveness. As this is an open source initiative, the software is also now publically available at https://github.com/dfci/matchminer. Conclusions: We have developed an open source computational platform that enables patient-specific matching and recruitment to precision medicine clinical trials at DFCI. We are actively seeking collaborators and plan to make CTML a multi-institution standard for encoding complex clinical trial eligibility in a computable form.

Utility of tumor genomic profiling in guiding targeted therapy and referral for clinical trials in the community practice.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18381-e18381
Author(s):  
Yiqing Xu ◽  
Jiang Yio ◽  
Amber Yang ◽  
Ashrei Bayewitz ◽  
Daniel Benasher ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Driver Mutations ◽  
Cancer Type ◽  
Tumor Type ◽  
Genomic Profiling ◽  
Community Practice ◽  
Match Trial

e18381 Background: Next-generation sequencing (NGS), which enables tumor genomic profiling with limited tumor specimen for the guidance of targeted therapy, has been widely used in oncology practice. It also reports mutations of which no approved therapy is available, but potential therapies approved in a different tumor type may be reasonable to try, based on molecular mechanisms or limited data, either in clinical trials or off trial treatment. The utility of this information in the community practice is unclear. Methods: We performed a retrospective analysis on the usage of NGS result on patients with lung or colorectal cancers treated between November 2011 and February 2018. Patients were identified from Foundation Medicine Company database and were linked to records at Maimonides. We evaluated if NGS was used to guide FDA-approved targeted therapy, potentially-useful targeted therapy not approved for the cancer type, or referral to a clinical trial. Results: 177 patients (lung ca = 119, colon ca = 58) were included. NGS identified 34 (28.6%) lung ca patients with driver mutations, (21 EGFR, 6 RET, 3 ALK, 2 MET amplification, 1 ROS1 and 1NTRK mutation), who were all given FDA-approved therapy. 70 (58.8%) patients had at least 1 target with an FDA-approved therapy for a different cancer; 89 (74.9%) had a mutation being studied in a clinical trial, and 48 patients were eligible for the NCI-MATCH trial. None received non-FDA-approved drugs and none was referred to clinical trials. In the colon cancer cohort, NGS identified alterations in KRAS (27), BRAF (5), ERBB2 mutation (2), ERBB2 amplification (1), MLH1 (1), MSH2 (1) and BRCA 2(1). Among them, one patient received BRAF inhibitors. 45 and 24 patients were eligible for phase I/II trials and NCI-MATCH trial respectively, and none was referred. Conclusions: NGS has a high efficiency of detecting driver mutations in lung cancer; but only reveals low frequencies of alterations otherwise not tested in colon cancer. The approach of prescribing un-approved targeted treatment based on theoretical mechanism of action was very uncommon, and the referral to clinical trials was rare in this community practice, both of which decreasing the utility value of NGS.

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