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. 2023 Jan:7:e2200342.
doi: 10.1200/PO.22.00342.

Programmatic Precision Oncology Decision Support for Patients With Gastrointestinal Cancer

Rachel B Keller  1 , Tali Mazor  2 , Lynette Sholl  3 , Andrew J Aguirre  1   4 , Harshabad Singh  1 , Nilay Sethi  1 , Adam Bass  1 , Ankur K Nagaraja  1 , Lauren K Brais  1 , Emma Hill  1 , Connor Hennessey  1 , Margaret Cusick  1 , Catherine Del Vecchio Fitz  2 , Zachary Zwiesler  2 , Ethan Siegel  2 , Andrea Ovalle  2 , Pavel Trukhanov  2 , Jason Hansel  2 , Geoffrey I Shapiro  1 , Thomas A Abrams  1 , Leah H Biller  1 , Jennifer A Chan  1 , James M Cleary  1 , Steven M Corsello  1 , Andrea C Enzinger  1 , Peter C Enzinger  1 , Robert J Mayer  1 , Nadine J McCleary  1 , Jeffrey A Meyerhardt  1 , Kimmie Ng  1 , Anuj K Patel  1 , Kimberley J Perez  1 , Osama E Rahma  1 , Douglas A Rubinson  1 , Jeffrey S Wisch  1 , Matthew B Yurgelun  1 , Michael J Hassett  1 , Laura MacConaill  3 , Deborah Schrag  1 , Ethan Cerami  2 , Brian M Wolpin  1 , Jonathan A Nowak  3 , Marios Giannakis  1   4
Affiliations

Programmatic Precision Oncology Decision Support for Patients With Gastrointestinal Cancer

Rachel B Keller et al. JCO Precis Oncol. 2023 Jan.

Abstract

Purpose: With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone.

Methods: We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration-approved label, and consideration of additional or orthogonal molecular testing.

Results: We reviewed genomic data and provided clinical recommendations for 506 patients with GI cancer who underwent tumor molecular profiling between January and June 2019 and determined follow-up using the electronic health record. Summary reports were provided to 19 medical oncologists for patients with colorectal (n = 198, 39%), pancreatic (n = 124, 24%), esophagogastric (n = 67, 13%), biliary (n = 40, 8%), and other GI cancers. We recommended ≥ 1 precision medicine clinical trial for 80% (406 of 506) of patients, leading to 24 enrollments. We recommended on-label and off-label targeted therapies for 6% (28 of 506) and 25% (125 of 506) of patients, respectively. Recommendations for additional or orthogonal testing were made for 42% (211 of 506) of patients.

Conclusion: The integration of precision medicine in routine cancer care through a dedicated multidisciplinary molecular tumor board is scalable and sustainable, and implementation of precision oncology recommendations has clinical utility for patients with cancer.

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Conflict of interest statement

Rachel B. Keller

Employment: Foundation Medicine

Lynette Sholl

Stock and Other Ownership Interests: Moderna Therapeutics

Consulting or Advisory Role: Genentech (Inst), Lilly (Inst), AstraZeneca

Research Funding: Roche/Genentech (Inst), Bristol Myers Squibb (Inst)

Andrew J. Aguirre

Stock and Other Ownership Interests: Riva Therapeutics

Honoraria: Phillips Gilmore Oncology

Consulting or Advisory Role: Merck, Alcon, Syros Pharmaceuticals, Arrakis Therapeutics, Mirati Therapeutics, Boehringer Ingelheim, Revolution Medicines, T-Knife, SERVIER, AstraZeneca, Riva Therapeutics

Research Funding: Syros Pharmaceuticals, Mirati Therapeutics, Deerfield Management, Novo Ventures, Revolution Medicines, Novartis, Bristol Myers Squibb/Celgene

Harshabad Singh

Research Funding: AstraZeneca/Daiichi Sankyo

Uncompensated Relationships: Seattle Genetics

Uncompensated Relationships: Natera

Nilay Sethi

Consulting or Advisory Role: Astrin Biosciences

Patents, Royalties, Other Intellectual Property: Compositions and methods for treating and/or identifying an agent for treating intestinal cancers 63/208313 filed on June 8, 2021

Adam Bass

Leadership: Signet Therapeutics, Earli, Helix Nanotechnologies

Stock and Other Ownership Interests: Signet Therapeutics, Earli, Helix Nanotechnologies

Consulting or Advisory Role: Roche, Silverback Therapeutics

Research Funding: Novartis, Repare Therapeutics, Bayer

Travel, Accommodations, Expenses: Lilly

Ankur K. Nagaraja

Employment: Novartis Institutes for BioMedical Research

Stock and Other Ownership Interests: Novartis

Emma Hill

Stock and Other Ownership Interests: Natera

Catherine Del Vecchio Fitz

Employment: Naveris

Stock and Other Ownership Interests: Naveris

Zachary Zwiesler

Employment: Invitae

Stock and Other Ownership Interests: Invitae

Travel, Accommodations, Expenses: Invitae

Ethan Siegel

Employment: 1upHealth

Stock and Other Ownership Interests: 1upHealth

Travel, Accommodations, Expenses: 1upHealth

Pavel Trukhanov

Stock and Other Ownership Interests: Nord Bio Inc

Jason Hansel

Stock and Other Ownership Interests: Beckman Coulter, Abbott Laboratories, Edwards Lifesciences, Johnson & Johnson/Janssen, Pacira Pharmaceuticals, Stryker, Thermo Fisher Scientific

Geoffrey I. Shapiro

Consulting or Advisory Role: Lilly, Pfizer, Merck Serono, Cybrexa Therapeutics, Bayer, Fusion Pharmaceuticals, Bicycle Therapeutics, Artios, Boehringer Ingelheim, Concarlo, Atrin Pharmaceuticals, Syros Pharmaceuticals, Zentalis, CytomX Therapeutics, Blueprint Medicines, Kymera, Janssen Oncology, XinThera, ImmunoMet

Research Funding: Pfizer (Inst), Bayer (Inst), Puma Biotechnology (Inst), Novartis (Inst), Cellceutix (Inst), Sanofi (Inst), Cyclacel (Inst), Mirati Therapeutics (Inst), AstraZeneca (Inst), GlaxoSmithKline (Inst), Lilly (Inst), Roche (Inst), CanBas (Inst), Merck Serono (Inst), Sierra Oncology (Inst), Syros Pharmaceuticals (Inst), Merck (Inst), Array BioPharma (Inst), Seattle Genetics (Inst), Clovis Oncology (Inst), Exelixis (Inst), Boehringer Ingelheim (Inst), Esperas Pharma (Inst), Amgen (Inst), Tango Therapeutics (Inst), Bristol Myers Squibb/Medarex (Inst), Senhwa (Inst), Biosplice (Inst), Cyteir (Inst), AbbVie (Inst)

Patents, Royalties, Other Intellectual Property: Patent No.: 9872874, Title: Dosage Regimen for Sapacitabine and Seliciclib, Issue Date: January 23, 2018; Provisional Patent No.: 62/538319, Title: Compositions and Methods for Predicting Response and Resistance to CDK4/6 Inhibition, Filed: July 28, 2017

Thomas A. Abrams

Stock and Other Ownership Interests: Jounce Therapeutics, Guardant Health, Mirati Therapeutics

Consulting or Advisory Role: Bristol Myers Squibb, Eisai, Merck, Bayer, Ipsen, Exelixis, SERVIER, Lilly

Jennifer A. Chan

Stock and Other Ownership Interests: Merck

Honoraria: Advanced Accelerator Applications, Ipsen

Consulting or Advisory Role: Advanced Accelerator Applications, Bayer, Pfizer, TerSera, Curium Pharma

Research Funding: Sanofi (Inst), Lilly (Inst)

Uncompensated Relationships: Camurus

James M. Cleary

Honoraria: Blueprint Medicines, Syros Pharmaceuticals, Incyte

Research Funding: Merck, Tesaro, AstraZeneca, Esperas Pharma, Merus (Inst), Roche/Genentech (Inst), BMS (Inst), Bayer, Apexigen, Arcus Biosciences

Travel, Accommodations, Expenses: Roche, Agios, Bristol Myers Squibb, Incyte

Steven M. Corsello

Research Funding: Bayer (Inst), Calico (Inst)

Patents, Royalties, Other Intellectual Property: Pending patent applications for drug uses and preclinical chemical matter. IP has been assigned to my institution

Andrea C. Enzinger

Consulting or Advisory Role: Five Prime Therapeutics, Merck, Astellas Pharma, Lilly, Loxo, Taiho Pharmaceutical, Daiichi Sankyo, AstraZeneca, Zymeworks, Takeda, Istari, Ono Pharmaceutical, Xencor, Novartis

Research Funding: Medtronic

Peter C. Enzinger

Consulting or Advisory Role: Merck, Astellas Pharma, Taiho Pharmaceutical, Loxo, Celgene, Zymeworks, Daiichi Sankyo, AstraZeneca, Takeda, Arcus Biosciences, Blueprint Medicines, Bristol Myers Squibb/Celgene, Coherus Biosciences, Five Prime Therapeutics, IDEAYA Biosciences, Istari, Legend Biotech, Lilly, Novartis, Ono Pharmaceutical, SERVIER, Turning Point Therapeutics, Xencor, ALX Oncology, Chimeric Therapeutics

Nadine J. McCleary

Research Funding: Bristol Myers Squibb Foundation

Jeffrey A. Meyerhardt

Honoraria: Cota Healthcare, Merck

Research Funding: Boston Biomedical (Inst)

Kimmie Ng

Honoraria: Bayer

Consulting or Advisory Role: Seattle Genetics, BiomX, Bicara Therapeutics, Redesign Health, GlaxoSmithKline, Bayer, Pfizer

Research Funding: Pharmavite (Inst), Revolution Medicines (Inst), Evergrande Group (Inst), Janssen (Inst)

Anuj K. Patel

Consulting or Advisory Role: Eisai

Research Funding: Analysis Group (Inst)

Travel, Accommodations, Expenses: Eisai

Kimberley J. Perez

Consulting or Advisory Role: Celgene, Eisai, Helsinn Therapeutics/QED Therapeutics, Lantheus Medical Imaging

Osama E. Rahma

Employment: Outcomes4me, AstraZeneca/MedImmune

Leadership: Outcomes4me, AstraZeneca/MedImmune

Stock and Other Ownership Interests: Outcomes4Me, AstraZeneca/MedImmune

Honoraria: Merck, Clinical Care Options, MI Bioresearch, PRMA Consulting, Leerink, Alaunus Global

Consulting or Advisory Role: Celgene, Alcimed, GfK, Merck, Five Prime Therapeutics, Putnam Associates, Defined Health, Puretech, Leerink, Genentech, Imvax, GlaxoSmithKline, Maverick Therapeutics, Bayer, Sobi

Research Funding: Amgen (Inst), Merck

Patents, Royalties, Other Intellectual Property: Pending patent (DFCI 2386.010; Inst), PD-1/PD-L1 (Inst)

Travel, Accommodations, Expenses: Merck, Clinical Care Options, Puretech, PRMA Consulting, Genentech

Douglas A. Rubinson

Consulting or Advisory Role: Augmenix, Boston Scientific, Instylla, Axial Therapeutics

Patents, Royalties, Other Intellectual Property: Royalty payments related to lentiviral shRNA technology invented in 2003

Open Payments Link: https://openpaymentsdata.cms.gov/physician/660913https://openpaymentsdata.cms.gov/physician/660913

Matthew B. Yurgelun

Matthew B. Yurgelun is a member of the JCO Precision Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.

Consulting or Advisory Role: Janssen

Research Funding: Janssen Oncology

Other Relationship: UpToDate

Michael J. Hassett

Research Funding: IBM

Deborah Schrag

Stock and Other Ownership Interests: Merck

Honoraria: Pfizer

Consulting or Advisory Role: JAMA—Journal of the American Medical Association

Research Funding: AACR (Inst), GRAIL (Inst)

Patents, Royalties, Other Intellectual Property: PRISSMM model is trademarked, and curation tools are available to academic medical centers and government under creative commons license

Other Relationship: JAMA—Journal of the American Medical Association

Ethan Cerami

Consulting or Advisory Role: Third Rock Ventures

Brian M. Wolpin

Honoraria: G1 Therapeutics, Celgene, Mirati Therapeutics

Consulting or Advisory Role: Genentech, G1 Therapeutics, BioLineRx, GRAIL, Celgene, Mirati Therapeutics

Research Funding: Celgene, Lilly, Novartis, Revolution Medicines

Jonathan A. Nowak

Research Funding: NanoString Technologies, Illumina

Marios Giannakis

Research Funding: Bristol Myers Squibb, Merck, SERVIER, Janssen

Patents, Royalties, Other Intellectual Property: Patent pending on biomarkers of immune response

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
GI TARGET program workflow: Genomic information is extracted from OncoPanels of patients with GI cancer and organized into a series of GI KBs to facilitate interpretation and review. A preliminary report is generated, which summarizes alterations of interest and current clinical trial options identified through MatchMiner. This information is reviewed in the context of relevant clinicopathologic information either through multidisciplinary molecular tumor board discussion or offline through molecular on-call. Consensus clinical recommendations and GI TARGET team discussion are summarized in the GI TARGET final report, which is e-mailed to the primary oncologist and uploaded to the EHR. AMP, amplification; CGS, clinical genomic scientist; Dx, diagnosis; EHR, electronic health record; GI AUTO, GI automated service; GI MO, GI medical oncologist; GI TARGET, Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors; INDEL, insertion/deletion; KB, knowledgebase; MP, molecular pathologist; SNV, single nucleotide variant; SV, structural variant; Tx, treatment; VUS, variant of unknown significance.
FIG 2.
FIG 2.
GI TARGET report content: (A) the PDF report includes (I) patient and sample information, (II) report summary, (III) GI cancer relevant genomic features, (IV) clinical trial matches from MatchMiner, and (V) additional report information. (II) is the most important section of the report and includes the "Summary of notable findings", which is a prioritized list of action items on the basis of integrated review of OncoPanel results in the context of relevant clinicopathologic information and additional commentary from the GI TARGET team that is useful for the primary oncologist. The "Summary of discussion" includes more detailed information expanding on the above recommendations. (IV) displays all clinical trial matches from MatchMiner on the basis of tier 1-3 SNV/INDELs, tier 1-3 SVs, and CNVs regardless of whether they are found in a gene listed in GI KB1 and, in the case of SNV/INDELs and SV, regardless of the interpretation (ie, oncogenic/likely oncogenic/VUS/neutral). Tier 4 SNV/INDELs are omitted from the GI TARGET report unless they are the basis of clinical trial matches, in which case they appear in a separate table titled "Additional Trial Matches Based on Variants of Unknown Significance." (B) Example of GI TARGET summary of notable findings from a pancreatic cancer case. CNVs, copy number variants; GI TARGET, Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors; KB, knowledgebase; SNV/INDELs, single nucleotide variants/insertions/deletions; SV, structural rearrangement variants; VUS, variant of unknown significance.
FIG 3.
FIG 3.
GI TARGET retrospective cohort: (A) case review flowchart and (B) cancer types in cohort. The number of cases and percentage of total cases (N = 510) for each cancer type are presented above each bar. GI TARGET, Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors.
FIG 4.
FIG 4.
Molecularly targeted therapy on clinical trials/on-label/off-label (GI TARGET retrospective cohort): (A) best response and time on treatment for 24 clinical trial enrollments associated with GI TARGET recommendations in the retrospective cohort. Toxicity/intolerance/adverse event are only noted if these contributed to the patient discontinuing treatment. An asterisk (*) denotes enrollment of a patient on two separate clinical trials (4th and 5th lines of therapy, respectively) on the basis of the same alteration (KRAS p.G12V). (B) Best response and time on treatment for eight patients receiving on- and off-label molecularly targeted therapy in the retrospective cohort. Toxicity/intolerance/adverse event are only noted if these contributed to the patient discontinuing treatment. A dagger (†) denotes a patient who received both neoadjuvant and adjuvant treatment. Two daggers (††) denote a patient who was on hospice before treatment start and elected to return to hospice because of worsening symptoms immediately after treatment start. AMP, amplification; CRC, colorectal cancer; ESO, esophagogastric cancer; FOLFOX, folinic acid + fluorouracil + oxaliplatin; ESO, esophagogastric cancer; GI TARGET, Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors; MMR-D, mismatch repair deficiency; NED, no evidence of disease; PAC, pancreatic cancer.
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References

    1. Weinstein JN, Collisson EA, Mills GB, et al. : The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45:1113-1120, 2013 - PMC - PubMed
    1. Mroz EA, Rocco JW: The challenges of tumor genetic diversity. Cancer 123:917-927, 2017 - PMC - PubMed
    1. Le Tourneau C, Paoletti X, Servant N, et al. : Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: Results of the feasibility part of the SHIVA trial. Br J Cancer 111:17-24, 2014 - PMC - PubMed
    1. Conley BA, Doroshow JH: Molecular analysis for therapy choice: NCI MATCH. Semin Oncol 41:297-299, 2014 - PubMed
    1. Johnson A, Zeng J, Bailey AM, et al. : The right drugs at the right time for the right patient: The MD Anderson precision oncology decision support platform. Drug Discov Today 20:1433-1438, 2015 - PMC - PubMed

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