Abstract 1906P
Background
The improved oncological outcomes with the emergence of targeted agents and immunotherapy have led to frequent combinations with radiotherapy (RT). High-quality data on toxicity of these combined treatments are scarce and consensus or evidence-based guidelines are lacking. The goal of this ESMO-ESTRO collaboration was to systematically review the existing literature and to develop consensus recommendations on the safety of combining RT with targeted agents or immunotherapy.
Methods
Ten systematic literature reviews were conducted regarding the safety of combining common targeted agents or immunotherapy with RT and a literature database was built. Fifty-seven international experts from both ESMO and ESTRO, divided into three groups, participated in three simultaneous Delphi consensus processes. Delphi statements were generated for 207 drug-radiotherapy scenarios. For each scenario, one of the following three safety level options was chosen: not combining, major treatment adaptation, or minor/no treatment adaptation. To accept a statement, 90% agreement was required during the first Delphi voting round, and 75% during the second round.
Results
Over 10.000 records were screened and full-text analysis was performed for 376 publications. Upon completing ten systematic literature reviews and the literature database, the Delphi consensus process was started. After finishing the two Delphi voting rounds, ≥75% agreement was reached on 99%, and ≥90% agreement was reached on 89% of all 207 consensus recommendations for ten types of targeted agents (Table). Table: 1906P
Final agreement rates
Drug target | Number of statements | ≥90% agreement (%) | 75-89% agreement (%) | No agreement (%) |
ALK | 18 | 15 (83) | 3 (17) | 0 (0) |
BRAF/MEK | 19 | 19 (100) | 0 (0) | 0 (0) |
CDK4/6 | 18 | 18 (100) | 0 (0) | 0 (0) |
EGFR | 20 | 17 (85) | 3 (15) | 0 (0) |
HER2 | 20 | 17 (85) | 3 (15) | 0 (0) |
mTOR | 18 | 17 (94) | 1 (6) | 0 (0) |
Multi-target | 21 | 16 (76) | 5 (24) | 0 (0) |
PARP | 18 | 16 (89) | 2 (11) | 0 (0) |
VEGF | 19 | 16 (84) | 2 (11) | 1 (5) |
Immunotherapy | 36 | 33 (92) | 2 (6) | 1 (3) |
Total | 207 | 184 (89) | 21 (10) | 2 (1) |
Conclusions
This first joint ESMO-ESTRO initiative provides evidence-based, multidisciplinary and pragmatic consensus recommendations regarding the safety of combining targeted agents or immunotherapy with RT. These will support clinicians during the clinical decision-making process and may prevent both undertreatment and unexpected synergistic toxicity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
ESMO, ESTRO.
Funding
KWF Dutch Cancer Society.
Disclosure
D. Martins Branco: Financial Interests, Personal, Invited Speaker, (03/02/2022 and 23/09/2022): AstraZeneca/DaiichiSankyo; Financial Interests, Personal, Full or part-time Employment: European Society for Medical Oncology; Financial Interests, Institutional, Funding, Institutional funding for observational research projects - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): Novartis; Financial Interests, Institutional, Funding, Institutional funding for an investigator-initiated clinical trial (NCT05075538) - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Other, Two industry-sponsored clinical trials (NCT01358877 and NCT03498716) - role: academic partner medical advisor at Institut Jules Bordet (01/01/2021 - 31/08/2023): F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding, Institutional funding for an investigator-initiated clinical trial (NCT03339843) - role: medical research fellow at Institut Jules Bordet (01/01/2021 - 31/08/2023): Eli Lilly; Non-Financial Interests, Member of Board of Directors: Associação de Investigação e Cuidados de Suporte em Oncologia - Portuguese MASCC affiliate; Non-Financial Interests, Leadership Role, Portuguese Young Oncologists Committee Chair: November 2020 - May 2022: Sociedade Portuguesa de Oncologia. D. De Ruysscher: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Philips Health, AstraZeneca; Financial Interests, Institutional, Coordinating PI: BMS, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Varian; Financial Interests, Funding: Olink; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Other, Advise group brain metastases NSCLC: Eli Lilly. J. Barriuso: Financial Interests, Personal, Invited Speaker: Pfizer, Ipsen, Nanostring, Servier, RAND; Financial Interests, Personal, Advisory Board: Nutricia, AAA; Non-Financial Interests, Project Lead: EORTC; Non-Financial Interests, Member of Board of Directors: GETNE; Non-Financial Interests, Principal Investigator: ENETS. A. Prelaj: Financial Interests, Personal, Other, Training of personnel: AstraZeneca, Italfarma; Financial Interests, Personal, Invited Speaker, The HIVE Project: Discussant: Roche; Financial Interests, Personal, Advisory Board, Advisory board in Lung Cancer project: BMS; Financial Interests, Personal, Other, Travel Grant: Janssen; Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: MEDSIR; Financial Interests, Institutional, Local PI: Bayer, BMS, Lilly, MSD; Financial Interests, Institutional, Coordinating PI: AstraZeneca, SPECTRUM. F. Lordick: Financial Interests, Personal, Advisory Board: Amgen, Astellas, BMS, Bayer, Beigene, Biontech, Eli Lilly, Elsevier, MSD, Novartis, Roche, Daiichi Sankyo, PAGE; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eli Lilly, Imedex, Incyte, MSD, MedUpdate, Medscape, Merck Serono, Roche, Servier, StreamedUp!, Daiichi Sankyo, Novartis, Art Tempi; Financial Interests, Personal, Writing Engagement: Deutscher Ärzteverlag, Iomedico, Springer-Nature; Financial Interests, Institutional, Research Grant: BMS, Gilead. G. Pentheroudakis: Financial Interests, Personal, Full or part-time Employment: ESMO. All other authors have declared no conflicts of interest.
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