TY - JOUR

T1 - Sustained improved survival of patients with metastatic melanoma after the introduction of anti-PD-1-based therapies

AU - Schina, Aimilia

AU - Pedersen, Sidsel

AU - Spenning, Anne Louise

AU - Laursen, Olivia Kaas

AU - Pedersen, Cecilia

AU - Haslund, Charlotte Aaquist

AU - Schmidt, Henrik

AU - Bastholt, Lars

AU - Svane, Inge Marie

AU - Ellebaek, Eva

AU - Donia, Marco

N1 - Publisher Copyright: © 2023 Elsevier Ltd

PY - 2023

Y1 - 2023

N2 - Background: The introduction of modern therapies improved the median survival of patients with metastatic melanoma (MM). Here, we determined the real-world impact of modern treatments on the long-term survival of MM. Methods: In a population-based study, we extracted all cases of MM diagnosed in four non-consecutive years marked by major changes in available 1st line treatments (2012, 2014, 2016, and 2018) from the Danish MM Database. Patients were grouped into “trial-like” and “trial-excluded” based on common trial eligibility criteria. Results: We observed a sustained improved survival of “trial-like” patients diagnosed in 2016 or in 2018, compared to 2012 or 2014, but no major differences in 2018 versus 2016. In contrast, while survival of “trial-excluded” patients in 2016 was better compared to 2014 and 2012, survival in 2018 was improved over all previous years. We then developed a prognostic model based on multivariable stratified Cox regression, to predict the survival of newly diagnosed MM patients. Internal validation showed excellent discrimination and calibration, with a time-area-under-the-curve above 0.79 at multiple time horizons, for up to four years after diagnosis. Conclusions: The introduction of modern treatments such as anti-PD-1 has led to a sustained, improved survival of real-world patients with MM, regardless of their eligibility for clinical trials. We provide an updateable prognostic model that can be used to improve patient information. Overall, these data highlight a positive population-based impact of modern treatments and can help health technology assessment agencies worldwide to evaluate the appropriateness of drug pricing based on known cost-benefit data.

AB - Background: The introduction of modern therapies improved the median survival of patients with metastatic melanoma (MM). Here, we determined the real-world impact of modern treatments on the long-term survival of MM. Methods: In a population-based study, we extracted all cases of MM diagnosed in four non-consecutive years marked by major changes in available 1st line treatments (2012, 2014, 2016, and 2018) from the Danish MM Database. Patients were grouped into “trial-like” and “trial-excluded” based on common trial eligibility criteria. Results: We observed a sustained improved survival of “trial-like” patients diagnosed in 2016 or in 2018, compared to 2012 or 2014, but no major differences in 2018 versus 2016. In contrast, while survival of “trial-excluded” patients in 2016 was better compared to 2014 and 2012, survival in 2018 was improved over all previous years. We then developed a prognostic model based on multivariable stratified Cox regression, to predict the survival of newly diagnosed MM patients. Internal validation showed excellent discrimination and calibration, with a time-area-under-the-curve above 0.79 at multiple time horizons, for up to four years after diagnosis. Conclusions: The introduction of modern treatments such as anti-PD-1 has led to a sustained, improved survival of real-world patients with MM, regardless of their eligibility for clinical trials. We provide an updateable prognostic model that can be used to improve patient information. Overall, these data highlight a positive population-based impact of modern treatments and can help health technology assessment agencies worldwide to evaluate the appropriateness of drug pricing based on known cost-benefit data.

KW - Immunotherapy

KW - Improved survival

KW - Metastatic melanoma

KW - Modern treatments

KW - Prognostic prediction model

KW - Real world evidence

KW - Survival prediction

U2 - 10.1016/j.ejca.2023.113392

DO - 10.1016/j.ejca.2023.113392

M3 - Journal article

C2 - 37924648

AN - SCOPUS:85175626680

VL - 195

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

SN - 0959-8049

M1 - 113392

ER -