TY - JOUR
T1 - Postapproval trials versus patient registries: comparability of advanced melanoma patients with brain metastases
AU - Ismail, Rawa K.
AU - Sikkes, Nienke O.
AU - Wouters, Michel W. J. M.
AU - Hilarius, Doranne L.
AU - Pasmooij, Anna M. G.
AU - van den Eertwegh, Alfonsus J. M.
AU - Aarts, Maureen J. B.
AU - van den Berkmortel, Franchette W. P. J.
AU - Boers-Sonderen, Marye J.
AU - de Groot, Jan Willem B.
AU - Haanen, John B. A. G.
AU - Hospers, Geke A. P.
AU - Kapiteijn, Ellen
AU - Piersma, Djura
AU - van Rijn, Roos S.
AU - Suijkerbuijk, Karijn P. M.
AU - ten Tije, Bert-Jan
AU - van der Veldt, Astrid A. M.
AU - Vreugdenhil, Art
AU - van Dartel, Maaike
AU - de Boer, Anthonius
N1 - Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval 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) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9-10.4) months compared to 7.3 (95% CI, 6.3-7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations.
AB - Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval 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) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9-10.4) months compared to 7.3 (95% CI, 6.3-7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations.
KW - advanced melanoma
KW - clinical outcomes
KW - patient registries
KW - postapproval trials
UR - http://www.scopus.com/inward/record.url?scp=85099076844&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/CMR.0000000000000707
DO - https://doi.org/10.1097/CMR.0000000000000707
M3 - Article
C2 - 33351553
SN - 0960-8931
VL - 31
SP - 58
EP - 66
JO - Melanoma Research
JF - Melanoma Research
IS - 1
ER -