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



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.



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.



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.
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark. Electronic address: marco.donia@regionh.dk.
Marco
M
Donia
Department of Oncology, Odense University Hospital, Odense, Denmark.
Marie Louise
ML
Kimper-Karl
Department of Oncology, Aarhus University Hospital, Denmark.
Katrine Lundby
KL
Høyer
Department of Oncology, Odense University Hospital, Odense, Denmark.
Lars
L
Bastholt
Department of Oncology, Aarhus University Hospital, Denmark.
Henrik
H
Schmidt
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Inge Marie
IM
Svane
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001685:Biological Factors / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary; D017326:Clinical Trials, Phase III as Topic; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000401:mortality / Q000628:therapy*; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D001685:Biological Factors
Immunotherapy; Metastatic melanoma; Patient selection; Phase III trials; Real-world patients