Abstract 849P
Background
Since the introduction of novel systemic therapies, the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is attributed to immune-surveillance. We investigated the relationship between TFDR and outcomes upon systemic treatment for advanced melanoma.
Methods
Analyses were performed on prospectively registered data from advanced cutaneous melanoma patients treated with first line BRAF(/MEK) inhibition or immune checkpoint inhibition (ICI) from the nationwide Dutch Melanoma Treatment Registry. Patients with a known primary tumor date were included. The association between TFDR and progression free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models with adjustment for age and type of therapy, both continuously (modelled linearly as well as flexibly using restricted cubic splines) and categorically.
Results
Patients received anti-PD-1-based treatment (n=1361 monotherapy and 483 in combination with anti-CTLA4) or BRAF(/MEK) inhibition (n=1618). Median follow-up was 32.8 months. Patients with a longer TFDR (>5 years) had a longer PFS (Hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.81-0.98) and OS (HR 0.83, 95%CI 0.75-0.92) than patients with TFDR <2 years. When stratifying for treatment, patients with a TFDR > 5 years (Table) had a longer median OS in both treatment cohorts. Based on a flexible spline fit and compared to synchronous disease, the hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Table: 849P
Median PFS and OS stratified by systemic treatment for the different TFDR categories
| Time to first distant recurrence | Logrank P-value | ||||
| < 2 years | 2-5 years | >5 years | |||
| Immune checkpoint inhibition | Median PFS, months (95%CI) | 7.3 (5.7-9.1) | 9.2 (7.4-12.2) | 10.0 (8.4-12.4) | 0.412 |
| Median OS, months (95%CI) | 25.0 (21.3-30.4) | 29.2 (30.6-35.7) | 37.3 (29.4-46.3) | 0.014 | |
| BRAF(/MEK) inhibition | Median PFS, months (95%CI) | 5.7 (5.4-6.2) | 5.8 (5.4-6.3) | 7.3 (6.4-8.1) | 0.006 |
| Median OS, months (95%CI) | 8.6 (7.4-9.8) | 8.1 (7.4-9.0) | 11.1 (10.2-12.2) | 0.004 |
Conclusions
Patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first line ICI or targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Medical Centre Utrecht.
Funding
For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organization The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted.
Disclosure
F. Van Den Eertwegh: Non-Financial Interests, Institutional, Advisory Role: Amgen, Pierre Fabre, Ipsen, Merck, Bristol Myers Squibb, MSD Oncology, Roche, Novartis, Sanofi, Pfizer; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Roche, Pfizer, Idera, TEVA, MSD Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Sanofi. J.W.B. de Groot: Non-Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. M. Aarts: Non-Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Roche, Eisai, Merck; Financial Interests, Institutional, Advisory Role: Astellas. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Expert Testimony: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Uniti Cars, co-founder Immagene BV; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, NanoString, 4SC. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Immunocore, Gadeta, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. G. Hospers: Non-Financial Interests, Institutional, Advisory Role: Amgen, Bristol Myers Squibb, Novartis, MSD, Roche, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Seerave. R.S. van Rijn: Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Expert Testimony: Roche. A.A.M. Van der Veldt: Non-Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, Merck. M. Boers-Sonderen: Non-Financial Interests, Institutional, Advisory Role: Pierre Fabre, MSD, Novartis. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: BMS, Novartis, Pierre Fabre, Merck, Delcath, Bayer; Financial Interests, Institutional, Invited Speaker: BMS. K.P.M. Suijkerbuijk: Financial Interests, Institutional, Advisory Board: Novartis, BMS, AbbVie, Pierre Fabre, msd; Financial Interests, Institutional, Invited Speaker: roche; Financial Interests, Institutional, Research Grant: Novartis, TigaTx. All other authors have declared no conflicts of interest.