The real-world impact of modern treatments on the survival of patients with metastatic melanoma

Marco Donia; Eva Ellebaek; Trine Heide Øllegaard; Lone Duval; Jens Bull Aaby; Lise Hoejberg; Ulrich Heide Køhler; Henrik Schmidt; Lars Bastholt; Inge Marie Svane

doi:10.1016/j.ejca.2018.12.002

The real-world impact of modern treatments on the survival of patients with metastatic melanoma

Marco Donia^*, Eva Ellebaek, Trine Heide Øllegaard, Lone Duval, Jens Bull Aaby, Lise Hoejberg, Ulrich Heide Køhler, Henrik Schmidt, Lars Bastholt, Inge Marie Svane

^*Corresponding author for this work

Department of Clinical Medicine

20 Citations (Scopus)

Abstract

Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the ‘real world’. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti–PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved. Patients were grouped into ‘trial-like’ and ‘trial-excluded’ based on the common trial eligibility criteria. In the ‘trial-like’ population (39% of all MM), the median overall survival (OS) was not reached in 2016 versus 18.8 months in 2014 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.35–0.75; p = 0.0005) and 16.5 months in 2012 (HR 0.41, 95% CI 0.27–0.63; p < 0.0001). In the ‘trial-excluded’ population (61% of all MM), 75% had brain metastases and/or (performance status) PS ≥ 2. Here, the median OS improved to 6.9 months in 2016 versus 5.2 months in 2014 (HR 0.66, 95% CI 0.52–0.84; p = 0.0008) and 4.2 months in 2012 (HR 0.66, 95% CI 0.52–0.84; p = 0.0007). Subgroup analysis of the BRAF wild-type population showed an improved 1-year survival rate in 2016 versus 2014 (35.9% vs 18.8%, p = 0.0153). In conclusion, the introduction of modern treatments has led to an improved survival of real-world patients with MM, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations which are not represented in pivotal trials.

Original language	English
Journal	European Journal of Cancer
Volume	108
Pages (from-to)	25-32
Number of pages	8
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2018.12.002
Publication status	Published - 2019

Keywords

Immunotherapy
Improved survival
Metastatic melanoma
Modern treatment era
Real-world evidence

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10.1016/j.ejca.2018.12.002

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@article{fa8961bd1f384feaa5b69876b14b9004,

title = "The real-world impact of modern treatments on the survival of patients with metastatic melanoma",

abstract = "Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the {\textquoteleft}real world{\textquoteright}. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti–PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved. Patients were grouped into {\textquoteleft}trial-like{\textquoteright} and {\textquoteleft}trial-excluded{\textquoteright} based on the common trial eligibility criteria. In the {\textquoteleft}trial-like{\textquoteright} population (39% of all MM), the median overall survival (OS) was not reached in 2016 versus 18.8 months in 2014 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.35–0.75; p = 0.0005) and 16.5 months in 2012 (HR 0.41, 95% CI 0.27–0.63; p < 0.0001). In the {\textquoteleft}trial-excluded{\textquoteright} population (61% of all MM), 75% had brain metastases and/or (performance status) PS ≥ 2. Here, the median OS improved to 6.9 months in 2016 versus 5.2 months in 2014 (HR 0.66, 95% CI 0.52–0.84; p = 0.0008) and 4.2 months in 2012 (HR 0.66, 95% CI 0.52–0.84; p = 0.0007). Subgroup analysis of the BRAF wild-type population showed an improved 1-year survival rate in 2016 versus 2014 (35.9% vs 18.8%, p = 0.0153). In conclusion, the introduction of modern treatments has led to an improved survival of real-world patients with MM, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations which are not represented in pivotal trials.",

keywords = "Immunotherapy, Improved survival, Metastatic melanoma, Modern treatment era, Real-world evidence",

author = "Marco Donia and Eva Ellebaek and {\O}llegaard, {Trine Heide} and Lone Duval and Aaby, {Jens Bull} and Lise Hoejberg and K{\o}hler, {Ulrich Heide} and Henrik Schmidt and Lars Bastholt and Svane, {Inge Marie}",

year = "2019",

doi = "10.1016/j.ejca.2018.12.002",

language = "English",

volume = "108",

pages = "25--32",

journal = "European Journal of Cancer, Supplement",

issn = "0959-8049",

publisher = "Pergamon",

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TY - JOUR

T1 - The real-world impact of modern treatments on the survival of patients with metastatic melanoma

AU - Donia, Marco

AU - Ellebaek, Eva

AU - Øllegaard, Trine Heide

AU - Duval, Lone

AU - Aaby, Jens Bull

AU - Hoejberg, Lise

AU - Køhler, Ulrich Heide

AU - Schmidt, Henrik

AU - Bastholt, Lars

AU - Svane, Inge Marie

PY - 2019

Y1 - 2019

N2 - Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the ‘real world’. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti–PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved. Patients were grouped into ‘trial-like’ and ‘trial-excluded’ based on the common trial eligibility criteria. In the ‘trial-like’ population (39% of all MM), the median overall survival (OS) was not reached in 2016 versus 18.8 months in 2014 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.35–0.75; p = 0.0005) and 16.5 months in 2012 (HR 0.41, 95% CI 0.27–0.63; p < 0.0001). In the ‘trial-excluded’ population (61% of all MM), 75% had brain metastases and/or (performance status) PS ≥ 2. Here, the median OS improved to 6.9 months in 2016 versus 5.2 months in 2014 (HR 0.66, 95% CI 0.52–0.84; p = 0.0008) and 4.2 months in 2012 (HR 0.66, 95% CI 0.52–0.84; p = 0.0007). Subgroup analysis of the BRAF wild-type population showed an improved 1-year survival rate in 2016 versus 2014 (35.9% vs 18.8%, p = 0.0153). In conclusion, the introduction of modern treatments has led to an improved survival of real-world patients with MM, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations which are not represented in pivotal trials.

AB - Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the ‘real world’. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatments (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4 and 2016: anti–PD-1: programmed cell death protein 1 and MEK inhibitors) were retrieved. Patients were grouped into ‘trial-like’ and ‘trial-excluded’ based on the common trial eligibility criteria. In the ‘trial-like’ population (39% of all MM), the median overall survival (OS) was not reached in 2016 versus 18.8 months in 2014 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.35–0.75; p = 0.0005) and 16.5 months in 2012 (HR 0.41, 95% CI 0.27–0.63; p < 0.0001). In the ‘trial-excluded’ population (61% of all MM), 75% had brain metastases and/or (performance status) PS ≥ 2. Here, the median OS improved to 6.9 months in 2016 versus 5.2 months in 2014 (HR 0.66, 95% CI 0.52–0.84; p = 0.0008) and 4.2 months in 2012 (HR 0.66, 95% CI 0.52–0.84; p = 0.0007). Subgroup analysis of the BRAF wild-type population showed an improved 1-year survival rate in 2016 versus 2014 (35.9% vs 18.8%, p = 0.0153). In conclusion, the introduction of modern treatments has led to an improved survival of real-world patients with MM, regardless of their eligibility to clinical trials and the BRAF status. These data support the application of modern treatments to patient populations which are not represented in pivotal trials.

KW - Immunotherapy

KW - Improved survival

KW - Metastatic melanoma

KW - Modern treatment era

KW - Real-world evidence

U2 - 10.1016/j.ejca.2018.12.002

DO - 10.1016/j.ejca.2018.12.002

M3 - Journal article

C2 - 30605822

AN - SCOPUS:85059227875

SN - 0959-8049

VL - 108

SP - 25

EP - 32

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

ER -

The real-world impact of modern treatments on the survival of patients with metastatic melanoma

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Keywords

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