Abstract 1120P
Background
Post-approval trials and patient registries have their pros and cons in generating post-approval data for medicine evaluation. No direct comparison between these post-approval data sources yet exists for advanced melanoma patients. We compared outcomes of patients with brain metastases (BM) treated with targeted therapies in post-approval trials with outcomes from a population-based patient registry. We aimed to explore whether a patient registry can complement or sometimes even replace post-approval trials.
Methods
Post-approval single-arm clinical trial data and real-world data from the Dutch Melanoma Treatment Registry (DMTR) were used. The study population consisted of patients with BM treated with targeted therapies (BRAF- or BRAF-MEK) in the first line. Two models were used to compare the data sources: a Cox hazard regression model and Propensity Score Matching (PSM).
Results
Four single-arm post-approval clinical trials on patients with advanced melanoma and BM were pooled, resulting in 467 patients. Real-world patients (n=602) had statistically significantly higher age, higher ECOG PS, more often metastases in ≥3 organ sites, and more often symptomatic BM than patients treated in post-approval trials. Lactate dehydrogenase (LDH) levels were similar. The unadjusted median overall survival (mOS) of post-approval clinical trial patients was 8.7 (95%CI; 8.1-10.4) months compared to 7.2 (95%CI; 6.5-7.7) months (p<0.01) for real-world patients. With the Cox model, survival was adjusted for prognostic factors, leading to a statistically insignificant difference in mOS of respectively 8.7 (95%CI; 7.9-10.4) compared to 7.3 (95%CI; 6.3-7.9) months for trial and real-world patients. PSM resulted in 310 (30.6%) matched patients with similar survival (p=0.9). Unmatched patients had high ECOG PS or symptomatic BM.
Conclusions
Real-world patients had baseline characteristics with higher risk, and prior to adjusting for this, a poorer survival than trial patients. Patient populations in a registry with similar entry criteria as patients treated in post-approval trials have the same outcomes. In this case, the DMTR could replace post-approval studies in the medicines evaluation after marketing authorization.
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 (institution), 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: BMS; 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: Bristol-Myers Squibb; Advisory/Consultancy: Celsius Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Gadeta; Advisory/Consultancy: GSK; Advisory/Consultancy: Immunocore; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Novartis; Advisory/Consultancy: Neogene; Advisory/Consultancy: Neon Therapeutics; Research grant/Funding (institution), not related to this paper: Bristol-Myers Squibb; Research grant/Funding (institution), not related to this paper: MSD; Research grant/Funding (institution), not related to this paper: GSK; Research grant/Funding (institution), not related to this paper: Neon Therapeutics; Shareholder/Stockholder/Stock options, not related to this paper: Neon Therapeutics. 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: Roche; Advisory/Consultancy: Novartis; 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.