The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

TY - JOUR

T1 - The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

AU - Donia, Marco

AU - Kimper-Karl, Marie Louise

AU - Høyer, Katrine Lundby

AU - Bastholt, Lars

AU - Schmidt, Henrik

AU - Svane, Inge Marie

N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of ‘real-world’ patients diagnosed with MM is not represented in these trials. Patients and methods The Danish MM Database contains data on the entire, unselected population of MM within a nationwide geographical area. A total of 276 unselected cases of MM (ocular melanoma excluded), referred for first oncological evaluation in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. Results Fifty-five percent of the total population with MM did not meet one or more eligibility criteria (‘not eligible’ group) at first evaluation. PS ≥ 2 or active/untreated known brain metastases accounted alone for 74% of non-eligibility cases. Median overall survival in the ‘not eligible’ group was 5.43 months versus 18.3 months for the eligible (p < 0.0001, hazard ratio (HR) 2.44), reflected by significantly worse baseline prognostic features. However, patients treated with immunotherapy had similar survival outcomes regardless of eligibility. Conclusion Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal a huge knowledge gap regarding the usefulness of new immunotherapies in the ‘real-world’ patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.

AB - Background Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of ‘real-world’ patients diagnosed with MM is not represented in these trials. Patients and methods The Danish MM Database contains data on the entire, unselected population of MM within a nationwide geographical area. A total of 276 unselected cases of MM (ocular melanoma excluded), referred for first oncological evaluation in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. Results Fifty-five percent of the total population with MM did not meet one or more eligibility criteria (‘not eligible’ group) at first evaluation. PS ≥ 2 or active/untreated known brain metastases accounted alone for 74% of non-eligibility cases. Median overall survival in the ‘not eligible’ group was 5.43 months versus 18.3 months for the eligible (p < 0.0001, hazard ratio (HR) 2.44), reflected by significantly worse baseline prognostic features. However, patients treated with immunotherapy had similar survival outcomes regardless of eligibility. Conclusion Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal a huge knowledge gap regarding the usefulness of new immunotherapies in the ‘real-world’ patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Biological Factors

KW - Brain Neoplasms

KW - Clinical Trials, Phase III as Topic

KW - Denmark

KW - Female

KW - Humans

KW - Immunotherapy

KW - Incidence

KW - Male

KW - Melanoma

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Patient Selection

KW - Randomized Controlled Trials as Topic

KW - Skin Neoplasms

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejca.2016.12.017

DO - 10.1016/j.ejca.2016.12.017

M3 - Journal article

C2 - 28335891

SN - 0959-8049

VL - 74

SP - 89

EP - 95

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

ER -