Genomic testing to enhance treatment choices and clinical trial accrual in metastatic colorectal cancer: Results of a prospective cohort study.

593 Background: Tumor genome sequencing is being used widely in clinical settings but its value to individual patients has not been well-studied. A prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and their impact on management decisions was conducted. Methods: Eligibility requirements included pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥18 years, and an ECOG PS of 0-2. Data for the colorectal cancer (CRC) subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes using FoundationOne (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 45 patients with CRC were analyzed. Median age was 60 years; 23 (51%) were female; 38 (84%) were white. Median time from consent to result was 25 (range, 7-75) days. One (2%) sample had inadequate tissue. A median of 5 (range, 2-19) mutations were detected per sample; APC (89%), TP53 (73%) and KRAS (66%) were most common. A therapy targeting an actionable alteration was recommended in 22 (51%) patients; 88% of these recommendations were for clinical trials. To date, 6 (33%) of 18 patients who switched management after test results received genomics-driven therapies (Table). Previously unknown RAS (KRAS Q61H, NRAS) mutations were detected in an additional 3 patients, influencing EGFR antibody use decisions. The commonest reason for non-receipt of therapy based on the test result was non-availability of clinical trials. Conclusions: Routine tumor genome profiling in CRC patients is feasible and influenced treatment decisions in a third of patients. A genomics tumor board for the interpretation of rapidly evolving information, and improved access to clinical trials of targeted agents are critical to the success of precision oncology. [Table: see text]

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Challenges with genomic testing in pancreaticobiliary cancers: Results of a prospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.314 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 314-314

Author(s):

Davendra Sohal ◽

Brian I. Rini ◽

Bassam N. Estfan ◽

Dale Randall Shepard ◽

Michael J. McNamara ◽

...

Keyword(s):

Clinical Trials ◽

Cohort Study ◽

Targeted Therapy ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Clinical Care ◽

Cleveland Clinic ◽

Tumor Board ◽

Genomic Testing ◽

Precision Oncology

314 Background: Therapeutic options for advanced pancreaticobiliary (PB) malignancies may be improved by genomics-driven therapies. We conducted a prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and therapeutic impact of such testing in PB cancers. Methods: Eligibility requirements included confirmed pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and an ECOG performance status of 0-2. Data for the PB cancer subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes in collaboration with Foundation Medicine, Inc. (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 228 patients were analyzed; 24 (11%) had PB cancers. For the latter subgroup, median age was 60 years; 14 (58%) were male; 20 (83%) were white. Twelve (50%) tumors were pancreatic, 11 (46%) from biliary tract/gallbladder, and 1 (4%) periampullary. Median time from consent to result was 24 (range, 3-84) days. Eight (33%) samples had inadequate tissue compared with 6/174 (3%) non-PB samples (p<0.001). Among patients with adequate tissue (n=16), a median of 3 (1-7) mutations were detected per sample; TP53 (50%), CDKN2A/p16 (44%) and KRAS (38%) were most common. A targeted therapy was recommended in 7 (44%) patients. Of these, 78% of recommendations were for specific clinical trials. To date, no patient with PB cancer has received a targeted therapy, compared with 6/45 (13%) patients with colorectal cancer (p=0.18). The most common reason for non-receipt of recommended targeted therapy was non-availability of clinical trials. Conclusions: Compared with other common solid tumors, genomic profiling in pancreaticobiliary cancers is challenged by paucity of diagnostic tissue collected during routine clinical care. Targeted therapy options (on-study or off-label) are few at this time. Precision oncology in pancreaticobiliary cancers will remain under-utilized until access to clinical trials is enhanced.

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Precision oncology experience at a tertiary care center.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18118 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18118-e18118

Author(s):

Meena Sadaps ◽

Pauline Funchain ◽

Petros Grivas ◽

Bassam N. Estfan ◽

Jame Abraham ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Real World ◽

Care Center ◽

Tertiary Care ◽

Cleveland Clinic ◽

Tumor Board ◽

Genomic Testing ◽

Precision Oncology ◽

Genomic Profiling

e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.

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