Abstract 237P
Background
Trial emulation applies RCT methodology to observational data, allowing estimation of long-term OS by mimicking existing RCTs. We emulated eight major RCTs in MBC to validate this approach using the ESME-MBC data.
Methods
We selected the emulated RCTs based on feasibility regarding power and key confounders among 13 pre-selected pivotal RCTs since 2000. Emulation was combined with appropriate adjustment using Stabilized Inverse Probability of Treatment Weight as the reference method, and alternative methods as sensitivity analyses. The RWD and RCT results were compared using three predefined agreement metrics.
Results
Table: 237P
OS estimates and agreement metrics
| Emulation sample size | Hazard Ratio [95% Confidence Interval] | Agreement | ||||
| RCT | Adjusted RWD | SA | EA | SD | ||
| PALOMA-3 (palbociclib) | 1, 139 | 0.81 [0.64-1.03] | 0.81 [0.69-0.95] | ✓ | ✓ | |
| PALOMA-2 (palbociclib) | 2, 413 | 0.96 [0.78-1.18] | 0.81 [0.72-0.92] | ✓ | ✓ | |
| MONALEESA-2 (ribociclib) | 1, 003 | 0.76 [0.63-0.93] | 0.55 [0.39-0.79] | ✓ | ✓ | |
| CLEOPATRA(pertuzumab) | 1, 062 | 0.68 [0.56-0.84] | 0.44 [0.36-0.55] | ✓ | ||
| EMILIA (T-DM1) | 836 | 0.68 [0.55-0.85] | 0.64 [0.52-0.77] | ✓ | ✓ | ✓ |
| RIBBON-1 (bevacizumab | 4, 703 | 1.11 [0.86-1.43] | 1.16 [1.07-1.25] | ✓ | ✓ | |
| AVADO (bevacizumab) | 873 | 1.03 [0.70-1.33] | 0.96 [0.77-1.20] | ✓ | ✓ | ✓ |
| BOLERO-2 (everolimus) | 904 | 0.89 [0.73-1.10] | 1.25 [1.06-1.47] |
SA, Full statistical significance agreement = when RWD and RCT HRs and CIs are on the same side of the null; EA, Estimate agreement = when the RWD HR falls within the 95% CI of the RCT; SD, Standardized difference agreement = difference in effect size between RCT and RWD relative to their standard deviation, achieved when the null hypothesis of no difference is not rejected, i.e. |z| ≤ 1.96.
Conclusions
These 8 emulations provide important insight into the real-world efficacy of major MBC drugs released in the past 15 years. Discrepancies may arise from residual confounding and drastic changes in prescription practices following drug approval. This approach provides opportunities to tackle challenges in demonstrating comparative effectiveness by applying external control arms.
Legal entity responsible for the study
Unicancer ESME.
Funding
Has not received any funding.
Disclosure
A. Antoine: Financial Interests, Personal, Other, 3-year PhD fellowship (since 2021) funded by Roche (France) and the National French Research and Technology Association (ANRT) via CIFRE doctoral fellowship no. 2020/1054: Roche France. D. Perol: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Boehringher Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead, IPSEN, Pfizer, Novartis, MSD, Roche, TAKEDA; Financial Interests, Personal, Advisory Board: BRENUS PHARMA; Other, travel expenses (esmo annual meeting madrid 2023): Novartis; Other, Travel Expenses (ESMO annual meeting Paris 2022): Roche. M. Robain: Financial Interests, Personal, Invited Speaker: Roche, Pfizer; Financial Interests, Personal, Other, Support for attending meeting: Menarini; Non-Financial Interests, Personal, Advisory Board: Horiana; Non-Financial Interests, Personal, Member of Board of Directors: AMMIS. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. R. Choquet: Financial Interests, Personal, Member: Roche. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. B. Ben Hadj Yahia: Financial Interests, Personal, Member: Roche. T. Grinda: Financial Interests, Personal, Invited Speaker: Cancérologie Pratique, Gilead, Pfizer. S. Delaloge: Financial Interests, Institutional, Advisory Board: Novartis, Sanofi, Gilead; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche Genentech, BMS, Sanofi; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Non-Financial Interests, Member of Board of Directors, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. All other authors have declared no conflicts of interest.