Abstract 1103P
Background
Recent results of patients treated with targeted therapies in clinical trials showed 5-year survival rates of 34% (dabrafenib/trametinib) and 39% (vemurafenib and cobimetinib). This study aimed to investigate the real-world survival of these patients and to identify characteristics of long-term survivors.
Methods
All advanced melanoma patients with a BRAF-V600 mutated tumor who received first-line BRAF-MEK therapy between 2013 and 2017 in the Netherlands were included. Overall survival (OS) was estimated with the Kaplan-Meier method. A multivariable Cox model was used to estimate the association of prognostic factors with OS. Long-term survival was defined as a minimal OS of 2 years from start therapy.
Results
Of 4.282 diagnosed patients, a total of 439 patients received first-line BRAF-MEK therapy. The median OS (mOS) was 11.8 (10.6-13.7) months, and 28% reached 2-year survival. Real-world patients often had symptomatic brain metastases (28%), stage IVm1c disease (87%), ECOG PS ≥2 (20%), ≥3 organ sites (59%), and elevated LDH of ≥250 U/I (31%) and ≥500 U/I (17%). Factors associated with improved survival were age <70 years, stage IIIc, IVm1a or IVm1b disease, normal LDH level, metastases in <3 organ sites, and no brain- or liver metastases. Gender and ECOG PS of ≥1 were not associated with improved survival. Long-term survivors (n=119) had an ECOG PS ≤1 (85%), less stage IVm1c (69%), normal LDH (62%), no brain metastases (78%), no liver metastases (80%) and <3 organ sites (62%). The median treatment duration of BRAF-MEK was 15.5 months. Subsequent immunotherapy was used in 66% of the long-term survivors, and a complete response occurred in 29%. The mOS of real-world patients treated with first-line BRAF-MEK with characteristics corresponding to the trial eligibility criteria (n=95) was 21.9 (17.3-35.9) months and the 2-year OS was 47%.
Conclusions
Long-term survival of real-world patients treated with first-line BRAF-MEK is significantly lower than of trial patients, mainly due to poorer baseline characteristics of real-world patients. Long-term survivors had more favorable characteristics compared to patients not reaching long-term survival. Based on these 2-year OS results, real-world 5-year survival is expected to be lower than in trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. van den Eertwegh: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre-Fabre; Research grant/Funding (institution), not related to this paper: Sanofi; Research grant/Funding (institution), not related to this paper: Roche; Research grant/Funding (self), not related to this paper: Bristol-Myers Squibb; Research grant/Funding (institution), not related to this paper: TEVA. M. Aarts: Advisory/Consultancy: Astellas; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis. M. Boers-Sonderen: Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis. J.W.B. de Groot: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Servier; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis. J.B.A.G. Haanen: Advisory/Consultancy: Aimm; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution), not related to this paper: Bristol-Myers Squibb; Advisory/Consultancy: Celsius Therapeutics; Advisory/Consultancy: Gadeta; Advisory/Consultancy, Research grant/Funding (institution), not related to this paper: GSK; Advisory/Consultancy: Immunocore; Advisory/Consultancy, Research grant/Funding (institution), not related to this paper: MSD; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Novartis; Advisory/Consultancy: Neogene; Advisory/Consultancy, Research grant/Funding (institution), Shareholder/Stockholder/Stock options, not related to this paper: Neon Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics. G.A.P. Hospers: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Research grant/Funding (institution), not related to this paper: Bristol-Myers Squibb; Research grant/Funding (institution), not related to this paper: Seerave. E. Kapiteijn: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Pierre Fabre; Research grant/Funding (institution), not related to this paper: Bristol-Myers Squibb. K.P.M. Suijkerbuijk: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre-Fabre; Honoraria (institution), not related to this paper: Novartis; Honoraria (institution), not related to this paper: Roche. A.A.M. Van der Veldt: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre-Fabre; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Eisai. All other authors have declared no conflicts of interest.