More than 50% of patients with metastatic melanoma are not represented in pivotal phase 3 immunotherapy registration trials

Abstract

Background: Recent randomized trials with strict patient ( pt) selection criteria led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). It is currently unknown how large is the proportion of real life pts with MM not represented in these trials Methods: Data from all MM patients referred in 2014 to assessment for systemic treatment were retrieved from the Danish MM Database. Data were available from two of three reference centers, where all resident pts diagnosed with MM are referred. A total of 194 cases (uveal melanoma was excluded) were retrieved, and 183 pts with sufficient records were included in the analysis. Seven pre-defined enrolment eligibility criteria, all employed in five recent randomized phase 3 immunotherapy trials, were analyzed Results: At 1st visit, the majority of pts (82%, n = 150) had confirmed cutaneous melanoma, 15% melanoma of unknown primary origin and 3% had mucosal melanoma. 32% of the pts had PS ≥ 2; 22% active/untreated known brain metastases; 22% significant comorbidities; 10% other malignancies in the past 5 years; 6% autoimmune diseases and 19% were on treatment with immunosuppressive drugs. 4 additional pts were not eligible because of the absence of target lesions. In total, 59% of the total population did not fulfil at least one enrolment criteria (non-eligible group). Median survival of the non-eligible group was 5.2 months vs 17.3 months for the eligible (p < 0.0001, HR 2.39), reflected by significantly poorer baseline prognostic features. In contrast, baseline characteristics of the eligible group were very similar to the average of patients (n = 3375) enrolled in five recent phase 3 trials. Median survival of the eligible group was comparable to the control group (ipilimumab) of patients enrolled in Keynote-006 trial, reflecting similar pts characteristics and treatment options Conclusions: At least half the patients evaluated for systemic treatment of MM are not represented in phase 3 registration immunotherapy trials. These data reveal a huge knowledge gap regarding the usefulness of new immunotherapies in the broader patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.