Treffer: Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review.

Background: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology.
Materials and Methods: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data.
Results: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data.
Conclusion: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.
(Copyright © 2023 European Society for Medical Oncology. All rights reserved.)

Disclosure AP declares training of personnel role for AstraZeneca and Italfarma; advisory board role for BMS, travel grant from Janssen; and speaker’s engagement for Roche. FT declares full or part-time employment with Politecnico di Milano as researcher and lecturer for high-level education; and as cofounder of MLcube. CG declares advisory board role for Amgen, Roche, Sanofi, Takeda; speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck-Sharp-Dohme, and Novartis; institutional funding from AstraZeneca and Bristol Myers Squibb; institutional research grant from Italian Ministry of Health; clinical trials PI for AstraZeneca and Roche; and non-remunerated activities as member or AIOM, AIOT, ASCO, FONICAP, IASLC, and ISLB. SER declares speaker’s engagement from Amgen, BMS, Astellas, and GSK; writer’s engagement from BMS and Amgen; and travel and accommodation from Janssen and MSD. LC-B declares full time employment with ESMO as Scientific and Medical division Fellow. JD declares consultant role for MJH Life Sciences at ASCO Clinical Congress Consultants at ASCO 2022. ATP declares advisory board role for Abbvie, Elevar, Prelude Therapeutics, and Privo; institutional research grant from Abbvie and Kura; and non-renumerated activity as PI for Adenoid Cystic Carcinoma Research Foundation and Cancer Research Foundation. GLR declares advisory board role for AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, and Sanofi; speaker’s engagement from Italfarnaco; institutional funding as local PI for Amgen, AstraZeneca, BMS, Celgene, GSK, MSD, Novartis, Roche and Sanofi. CP declares personal fees from Italfarmaco, AstraZeneca, BMS, Merck Sharp and Dohme, and Janssen; and institutional funding from Novartis. ST declares speaker’s engagement from IDEA Pharma, Merck, MSD, Roche, and Ventana; institutional funding from Andy Quick Charitable fund, Complete genomics, CRUK, CRUK training and career development board, CRUK Welcome Trust, Harry J Lloyd Charitable Trust Career Development Award, NIHR, RMH/ICR/BRC/Imperial AHSC/Faculty of Medicine, Rosetrees Trust, The Francis Crick Institute, The Robert McAlpine Foundation, and Ventana. MK declares advisory board role for Bayer, MSD, Pierre Fabre, Servier; speaker’s engagement for BMS, Merck; institutional funding from Amgen, BMS, Merck, Nordic Farma, Novartis, Pierre Fabre, Servier; institutional research grant from Bayer, Bristol Myers Squibb, Personal Genomics Diagnostics, Pierre Fabre, Roche, Servier, Sirtex; trial chair for Servier; non-remunerated activities for Leadership Role for Dutch Colorectal Cancer Group and ESMO; advisory role for KWF, Patient representative organization (Kanker.nl), ZiNNL; and non-remunerated activity as ESMO faculty member. SD declares advisory board role for AstraZeneca, Besins Healthcare, Cellectis, Elsan, Isis/Servier, Novartis, Orion, Pierre Fabre, Rappta, Sanofi; speaker’s engagement for AstraZeneca, Exact Sciences, Gilead, Lilly, MSD, Pfizer, Seagen; institutional funding as steering committee member for AstraZeneca, BMS, Pfizer, Puma, Sanofi, Roche Genentech; institutional funding as local PI for Orion; institutional funding as coordinating PI for Taiho; institutional funding from GE; non-remunerated activity as PI for European Commission; and non-remunerated activity as Board of Directors member for SFSPM. JNK declares advisory board role for DoMore Diagnostics, Owkin, and Panakeia; and speaker’s engagement from Eisai, Fresenius, and MSD. FGMDeB declares speaker’s engagement from Ambrosetti, Amgen, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, Merck Group, MSD, Nadirex, Pfizer, Roche, Sanofi, Seagen, and Servier; consultation/advisory role from Mattioli 1885, AstraZeneca, BMS, EMD Serono, Incyte, Menarini, MSD, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi, and Taiho; funding as coordinating PI from Basilea Pharmaceutica International AG, BMS, DAICHI SANKIO Dev. Limited, Exelixis Inc, F. Hoffman-LaRoche Ltd, Ignyta Operating INC, IQVIA, Janssen-Cilag International NV, Kymab, LOXO Oncology Incorporated, MedImmune LCC, Merck KGaA, Merck Sharp & Dohme Spa, MSD, Novartis, Pfizer, and Tesaro; and think tank funding from MCCann Health. MCG declares speaker’s engagement from AstraZeneca, ecancer, GrupoPacifico-Secretaria Tecnica ICAPEM/AstraZeneca, Medscape, MSD, MSD Italia, S.O.S S.r.l, WebMD, WebMD Oncology/Takeda; consultation/advisory role from AstraZeneca/MedImmune, Daiichi Sankyo, AstraZeneca Poland, AstraZeneca UK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Mirati Therapeutics, MSD, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi/Prex, Sanofi Genzyme corporation, Seagen International GmbH, and Takeda; institutional funding as local PI for Phase III studies from Amgen, AstraZeneca, Bluprint, BMS, GlaxoSmithkline, Incyte Corporation, IPSEN Bioscience, MedImmune LCC, Novartis, Roche, and Sanofi; institutional funding as local PI for Phase II studies from AstraZeneca, Celgene Corporation, Daiichi Sankyo Development, MedImmune LCC, Merck KGaA, Merck Serono, Spectrum Pharmaceuticals, and Turning Point Therapeutics; institutional funding as local PI for Phase I studies from Exelixis Inc., Janssen; institutional funding as local PI from Bayer, Janssen, Merck, Pfizer, Otsuka Pharmaceutical Italy; institutional funding as Coordinating PI from AstraZeneca, MSD; steering committee member of the MK-3475 KN671 Steering Committee (KEYNOTE-671) from MSD, MK-3475 KN671 Steering Committee from MSD, Steering Committee ML41118 from Roche, and steering committee of Pfizer Global Lung Cancer Educational Programme; personal financial interests as PACIFIC-R Scientific Committee from AstraZeneca, PACIFIC-R Global Scientific Committee from AstraZeneca, Pacific 6 International Coordinating Investigator from AstraZeneca, steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019, GSK-Garassino-ZEAL Steering Committee 2020-23, GSK Lung Cancer Global Council, Jannesen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer, Seattle Genetics Lung Cancer Platform Study; travel, accommodations and expenses from AstraZeneca, Pfizer, and Roche; non-remunerated activities as principal investigator of AO Spedali Civili Brescia, Eli Lilly Studio TYME trial, European Thoracic Oncology Platform (ETOP) phase III trial, GOIRC Studio CHANCE trial, GOIRC RAME trial, GUSTAVE-ROUSSY PARIGI LIPI TRIAL, Istituto dei Tumori Pascale MILES 5 trial, Istituto dei Tumori Pascale IND227 trial, Istituto dei Tumori Pascale Beverly trial, Istituto Nazionale dei Tumori Progetto Timoma trial, Istituto Nazionale dei Tumori APOLLO trial, Istituto Nazionale dei Tumori Bando finalizzata Mesotelioma trial, Istituto Nazionale dei Tumori POST-ALK trial, Istituto Nazionale dei Tumori TERAVOLT trial, Istituto Nazionale dei Tumori FAME trial, MSD People, Pfizer STYLE trial, and Sant’Orsola Malpighi Creta trial; non-remunerated activities as member of AIOM, AIOT, ASCO, EMA Scientific Advisory Group, ESMO, IPOP, TUTOR, WCLC, Women for Oncology Italy; and non-remunerated activities as Scientific Programme Committee of AACR. GP declares full time employment from ESMO. ALGP declares personal financial interests for stocks/shares as cofounder of Agade s.r.l. and AllyArm s.r.l; institutional financial interests for co-funding of the Professorship Chair by Associazione Univerlecco and Congregazione Suore Infermiere dell’Addolorata; institutional financial interests for licensing/royalties as co-inventor of Patent No. 10201900000848 (Load compensation device, registered with Politecnico di Milano, surrendered in January 2023 with a royalty return plan), Patent No. 102018000006950 (System for detection and kinematic monitoring of body movements in water, and relative method, registered with Politecnico di Milano and Fondazione per la Ricerca Scientifica Termale; PCT/EP2019/067618) and Patent No. 102017000027918 (Device for controlled assistance of the grip; PCT/IB2018/051652); and non-financial interests as a member of the International Conference of Rehabilitation Robotics, member of the Institute of Electrical and Electronics Engineers (IEEE), IEEE Robotics and Automation Society, IEEE Engineering in Medicine and Biology Society and IEEE Women in Engineering. All other authors have declared no conflicts of interest.