Abstract 850P
Background
Adjuvant treatment with dabrafenib/trametinib (dab/tram) and anti-PD-1 antibodies (PD1) reduce the risk of recurrence and distant-metastasis in patients with stage III melanoma. Applying stage and treatment-specific clinical trial data to patients at time points during the course of treatment to inform follow-up and prognostication is difficult. We therefore developed a risk-prediction tool to aid clinical management that provides recurrence risks, adjusted for time survived, for patients with resected stage III melanoma at commencement of therapy as well as at various timepoints thereafter.
Methods
Kaplan-Meier survival curves (recurrence-free and distant-metastasis free survival) information were extracted from three clinical trials (COMBI-AD, CheckMate-238, Keynote-054/EORTC-1325). Individual curves were digitalized separately, and individual patient data reconstructed. Recurrence (any, distant), and time to event were obtained for each individual. Conditional survival analysis estimated the risks of recurrence from commencement of treatment and for survivors at 3-monthly time points, stratified by stage and intervention.
Results
Data from 2032 patients with resected AJCC v8 stage IIIB-D melanoma treated with dab/tram (n=384, median F/U 61mo, 95% CI 60-63), PD1 (n=816, median F/U 41mo, 95% CI 40-42) or observation (n=832, median F/U 41mo, 95% CI 40-43) were derived. Example results are shown (Table). An online calculator was developed. Table: 850P
| AJCC v8 Stage | Adjuvant intervention | Overall risk of recurrence* with intervention (%) | Remaining risk of recurrence* (%) if recurrence free at: | |||
| 6mo | 12mo | 24mo | 36mo | |||
| IIIB | Observation | 51% | 42% | 29% | 10% | 6% |
| Dab/Tram | 40% | 41% | 37% | 20% | 12% | |
| PD1 | 30% | 20% | 14% | 10% | 7% | |
| IIIC | Observation | 62% | 53% | 38% | 18% | 13% |
| Dab/Tram | 45% | 51% | 45% | 23% | 10% | |
| PD1 | 45% | 35% | 26% | 14% | 12% |
* Risk over F/U period as referred to in the results. Differing follow up periods from different trials precludes accurate comparison of risk between interventions.
Conclusions
This tool provides risks of recurrence in an easy-access location, which should guide discussions with patients about their current risk of recurrence with or without therapy at baseline and during their treatment journey, and appropriate surveillance. More data will be incorporated as they become available, further increasing the accuracy of the tool over time.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Melanoma Institute Australia.
Funding
Has not received any funding.
Disclosure
A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers-Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. I. Pires da Silva: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Speaker’s Bureau: Novartis. M.S. Carlino: Financial Interests, Personal, Advisory Role: Amgen, Bristol Myers Squibb, Eisai, Ideaya, Merck Sharp and Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche; Financial Interests, Personal, Other: Bristol Myers Squibb, Merck Sharp and Dohme, Novartis. R.A. Scolyer: Financial Interests, Personal, Advisory Role: F. Hoffman-La Roche Ltd., Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck, Sharp & Dohme, NeraCare, Amgen Inc., Bristol Myers Squibb, Myriad Genetics, GlaxoSmithKline; Financial Interests, Personal, Research Grant: NHMRC Fellowship. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. All other authors have declared no conflicts of interest.