61MO - Perceptions of healthcare professionals and regulators on the use of real-world data as external comparators in late-stage oncology single-arm trials

Background

Real-world data (RWD) have potential applications for complementing other data sources, including as external comparators for single-arm trials (SAT). We aimed to explore perceptions about this methodology in the setting of advanced cancer of high unmet medical need.

Methods

A cross-sectional survey of healthcare professionals (HCP) and regulators was conducted between May-Sept’24. Beliefs related to advantages/disadvantages of randomised controlled trials (RCT) and RWD studies were measured. Participants were exposed to 4 different hypothetical scenarios where RWD external comparators were used to contextualize results in advanced cancer with no effective alternatives and historical median overall survival (mOS) of 3 months (mos). Scenarios were combinations of mOS gain 1.5 vs 3 mos, using low- vs high-quality RWD. SAT with no external comparator and RCT (mOS gain 1.5 vs 3 mos) were control scenarios. For each scenario, convincingness of OS benefit and acceptability of increase in grade 3-4 toxicity were surveyed.

Results

A total of 103 HCP and 116 regulators participated. Compared to regulators, HCP rated higher familiarity with RWD (73% vs 43%) and that RWD studies have more advantages than disadvantages (48% vs 13%). Convincingness of OS benefit was higher in the 2 scenarios using high-quality RWD (mOS gain: 3 mos, 69%; 1.5 mos, 34%) than SAT without external comparators (24%). The highest trust was measured for RCT (mOS gain: 3 mos, 92%; 1.5 mos, 79%). The 2 scenarios with low-quality RWD resulted in more unconvinced participants (mOS gain: 3 mos, 59%; 1.5 mos, 73%) than the SAT scenario (54%). Although the trust in OS benefit of scenarios with RWD external comparator was associated with positive rating of RWD studies advantages, the use of high-quality RWD increased convincingness for both HCP and regulators. Higher measured trust in mOS effect size was associated with higher acceptability of an increase in severe toxicity.

Conclusions

HCP and regulators share a positive perception of the use of high-quality RWD as an external comparator to SAT of advanced cancer of high unmet medical need. Quality attributes in RWD studies must be clearly defined for the streamlined use of this methodology.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors - the views presented are those of the authors and do not represent the views of their respective organisations.

Funding

Has not received any funding.

Disclosure

D. Martins-Branco: 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, Personal, Member of Board of Directors, (10/2022 - 10/2024): Associação de Investigação e Cuidados de Suporte em Oncologia - Portuguese MASCC affiliate; Non-Financial Interests, Personal, Member, ID 375701: American Society of Clinical Oncology; Non-Financial Interests, Personal, Member, ID 704: Sociedade Portuguesa de Oncologia; Non-Financial Interests, Personal, Member, ID 792: Associação Portuguesa de Cuidados Paliativos; Non-Financial Interests, Personal, Member, ID 5546: Multinational Association of Supportive Care in Cancer. T.C. El-Galaly: Non-Financial Interests, Personal, Member: EHA. A. Valachis: Financial Interests, Institutional, Research Grant, Research Grant for a research project on Molecular profiling of triple negative breast cancer: Roche; Financial Interests, Institutional, Invited Speaker, PRODAT trial: Novartis; Financial Interests, Institutional, Invited Speaker, CHECKMATE-401 trial: Bristol-Myers-Squibb; Financial Interests, Institutional, Invited Speaker, CHECKMATE-76K trial: Bristol-Myers-Squibb; Financial Interests, Institutional, Invited Speaker, TELEPIK trial: Novartis; Financial Interests, Institutional, Invited Speaker, DESTINY-Breast09 trial: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD. D. Trapani: Other, Personal, Other, EMA Healthcare Professional Working Party (HCPWP), member: European Medicines Agency (EMA); Other, Personal, Other, EML Cancer Medicines Working Group (CMWG), member: World Health Organization (WHO); Other, Personal, Other, Strategic Advisory Group of Experts on In Vitro Diagnostics (SAGE IVD), chair: World Health Organization (WHO). M. Di Maio: Financial Interests, Personal, Advisory Board, Consultancy about clinical trial methodology and clinical trial results interpretation: Novartis; Financial Interests, Personal, Advisory Board, Consultancy about immunotherapy in SCLC: Roche; Financial Interests, Personal, Advisory Board, Consultancy about role and interpretation of patient-reported outcomes and quality of life in clinical trials: Takeda; Financial Interests, Personal, Advisory Board, Advisory board about the role of chemotherapy and hormonal treatment in hormone-sensitive prostate cancer: Janssen; Financial Interests, Personal, Advisory Board, Consultancy about the results obtained with lorlatinib and dacomitinib in advanced non-small cell lung cancer: Pfizer; Financial Interests, Personal, Advisory Board, Consultancy about role of osimertinib as adjuvant treatment of NSCLC: AstraZeneca; Financial Interests, Personal, Advisory Board, Participation in advisory boards about olaparib in pancreatic cancer, about olaparib in prostate cancer, and about immunotherapy in lung cancer: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board, Consultant for the new indication of avelumab in urothelial cancer: Merck Serono; Financial Interests, Personal, Advisory Board, Advisory board about treatment of gastric cancer: Amgen; Financial Interests, Personal, Advisory Board, Lesson for the personnel of the drug company about quality of life, patient-reported outcomes and methodological aspects of clinical trials: GlaxoSmithKline; Financial Interests, Personal, Advisory Board, Advisory board about trastuzumab deruxtecan in gastric cancer: Daiichi Sankio; Financial Interests, Personal, Advisory Board, Advisory board about Moovcare and remote monitoring of symptoms in patients with cancer: Viatris; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Institutional, Research Grant, Financial support and drug supply for the Meet-URO12 trial (niraparib as maintenance treatment of urothelial carcinoma after first-line treatment with platinum-based chemotherapy): Tesaro - GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker, Local PI of trial with tislelizumab in hepatocellular carcinoma: Beigene; Financial Interests, Institutional, Invited Speaker, Local PI of a trial with cabozantinib and atezolizumab in advanced HCC: Exelixis; Financial Interests, Institutional, Invited Speaker, Local PI of a trial with atezolizumab and bevacizumab in advanced HCC: Roche; Financial Interests, Institutional, Invited Speaker, Local PI of trials with pembrolizumab in hepatocellular carcinoma: Merck Sharp & Dohme; Financial Interests, Institutional, Invited Speaker, Local PI of a trial with sasanlimab in NMI bladder cancer: Pfizer; Non-Financial Interests, Personal, Leadership Role, President Elect (2023-2025): AIOM (Italian Association of Medical Oncology). P. Mol: Financial Interests, Personal, Full or part-time Employment, I am a professor of regulatory science at an academic medical center in the Netherlands.: University Medical Center Groningen; Financial Interests, Personal, Full or part-time Employment, I am a member of the European Medicines Agency Committee of Medicinal Products for Human use (CHMP).: Dutch Medicines Evaluation Board. M. Kaiser: Financial Interests, Personal, Advisory Board: Abbvie, GSK, Pfizer, Roche, Regeneron, Poolbeg, Celgene/BMS, Sanofi; Financial Interests, Institutional, Research Grant: Johnson and Johnson, Celgene/BMS; Non-Financial Interests, Personal, Advisory Role, Chair Clinical Trials Committee: Blood Cancer UK. M. Koopman: Financial Interests, Institutional, Advisory Board, advisory board and speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: MSD, Bayer; Financial Interests, Institutional, Advisory Board, Advisory Board, speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck, BMS, servier; Financial Interests, Institutional, Research Grant: servier, Roche, Bayer, Bristol Myers Squibb, Merck, Personal Genomics Diagnostics, sirtex, Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre, amgen, Nordic Farma, Novartis, merck, servier, BMS; Non-Financial Interests, Personal, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; Non-Financial Interests, Personal, Other, ESMO faculty member for the Gastro-Intestinal Tumours – colorectal cancer: ESMO; Non-Financial Interests, Personal, Advisory Role, expert member of committee “regie op registers dure geneesmiddelen” ZINNL: ZiNNL; Non-Financial Interests, Personal, Advisory Role, CRC expert on Kanker.nl platform for answering online CRC questions of CRC (non) patients: Patient respresentative organisation (Kanker.nl); Non-Financial Interests, Personal, Leadership Role, chair of RWD & DH working group: ESMO; Other, Personal, Other, PI of the Dutch Prospective Colorectal Cancer Cohort study: PLCRC project. N. Cherny: Financial Interests, Personal, Stocks/Shares, Stock options 0.2% In digital health company compesation for consultancy role: Canopy Care. G. Pentheroudakis: Financial Interests, Personal, Full or part-time Employment, Chief Medical Officer: ESMO; Non-Financial Interests, Personal, Member: ASCO, Hellenic Cooperative Oncology Group (HeCOG), Hellenic Society of Medical Oncology. All other authors have declared no conflicts of interest.