Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

F Mosele 1, J Remon 2, J Mateo 3, C B Westphalen 4, F Barlesi 1, M P Lolkema 5, N Normanno 6, A Scarpa 7, M Robson 8, F Meric-Bernstam 9, N Wagle 10, A Stenzinger 11, J Bonastre 12, A Bayle 13, S Michiels 12, I Bièche 14, E Rouleau 15, S Jezdic 16, J-Y Douillard 16, J S Reis-Filho 17, R Dienstmann 18, F André 19

Affiliations

PMID: 32853681
DOI: 10.1016/j.annonc.2020.07.014

Abstract

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Keywords: genomic alterations; metastatic cancers; next-generation sequencing (NGS).

Conflict of interest statement

Disclosure JR: advisory: Merck Sharp & Dohme (MSD), Boehringer, Bristol-Myers Squibb (BMS), AstraZeneca, Roche; speaker's bureau: Pfizer; travel support: OSE Immunotherapeutics SA, BMS, AstraZeneca, Roche. JM: advisory board: Amgen, AstraZeneca, Clovis Oncology, Janssen, MSD and Roche-Foundation Medicine; research funding: AstraZeneca and Pfizer Oncology; principal investigator of several industry sponsored clinical trials. CBW: personal and speakers' fees, reimbursement for travel and accommodation and honoraria for participance in advisory boards from Bayer, Celgene, Ipsen, MedScape, Rafael Pharmaceuticals, RedHill, Roche, Servier, Shire/Baxalta and Taiho; scientific grant support by Roche. FB: personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda. MPL: research grants (to hospital): MSD, Astellas, JnJ, Sanofi; advice: Roche, Bayer, Amgen, JnJ, Sanofi, Servier, Pfizer, Incyte. NN: speaker's fee and/or advisory boards: Amgen, AstraZeneca, Bayer, Biocartis, BMS, Boehringer Ingelheim, Eli Lilly, Ilumina, Incyte, MERCK, MSD, Qiagen, Roche, Thermofisher, Sanofi; institutional financial interests (financial support to research projects): AstraZeneca, Biocartis, BMS, Illumina, Merck, Qiagen, Roche, Sysmex, Thermofisher; non-financial interests: President of the International Quality Network for Pathology (IQN Path); President of the Italian Cancer Society (SIC). ASc: speakers bureau: Ypsen, Astra Zeneca, Amgen, MSD, GSK; consulting: INCYTE Biosciences. MR: consulting or advisory: AstraZeneca (uncompensated), Change Healthcare, Daiichi-Sankyo (uncompensated), Epic Sciences (uncompensated), Merck (uncompensated), Pfizer (uncompensated); research funding: AbbVie (institution), AstraZeneca (Institution), Invitae (Institution, in-kind), Merck (Institution), Pfizer (institution); travel, accommodation, expenses: AstraZeneca, Merck; editorial services: AstraZeneca, Pfizer. FM-B: consulting: Aduro BioTech Inc., Alkermes, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd, Genentech Inc., IBM Watson, Jackson Laboratory, Kolon Life Science, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Samsung Bioepis, Seattle Genetics Inc., Tyra Biosciences, Xencor, Zymeworks; advisory committee: Immunomedics, Inflection Biosciences, Mersana Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Silverback Therapeutics, Spectrum Pharmaceuticals, Zentalis; sponsored research: Aileron Therapeutics, Inc., AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd, Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Millennium Pharmaceuticals Inc., Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co.; honoraria: Chugai Biopharmaceuticals, Mayo Clinic, Rutgers Cancer Institute of New Jersey; other (Travel Related): Beth Israel Deaconess Medical Center. NW: research grant from Puma Biotechnology; scientific advisory board and stockholder for Relay Therapeutics; advisor to Eli Lilly. ASt: advisory board/speakers bureau: Astra Zeneca, Eli Lilly, Bayer, BMS, Illumina, Janssen, MSD, Pfizer, Roche, Seattle Genetics, Thermo Fisher; Grants: Bayer, BMS, Chugai. JB: travel support: BMS; consulting fees: BMS, MSD, Astellas. SM: statistical advice: IDDI and Janssen Cilag; Independent Data Monitoring Committee member: Hexal, Steba, IQVIA, Roche, Sensorion, Biophytis, Servier, Yuhan. IB: speaker’s fee: AstraZeneca. ER: board participation: AstraZeneca, BMS, Roche; travel funding: AstraZeneca, BMS. JSR-F: paid consultant: Goldman Sachs, REPARE Therapeutics, and Paige.AI; member of the scientific advisory board: REPARE Therapeutics, Paige.AI, and Volition Rx; member of the Board of Directors: Group Oncoclinicas; ad hoc member of the scientific advisory board: Roche Tissue Diagnostics, Roche, Genentech, Novartis, and Invicro; owns shares: REPARE Therapeutics. RD: advisory: Roche, Boehringer Ingelheim; speaker’s fee: Roche, Ipsen, Amgen, Servier, Sanofi, Merck Sharp & Dohme; research grants: Merck and Pierre Fabre. FA: research grants and talks/advisory boards compensate to the hospital: Roche, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo, Lilly. All remaining authors have declared no conflicts of interest.