medwireNews: Over half of patients with metastatic melanoma do not meet eligibility criteria for participation in phase III clinical trials of immunotherapy agents, highlight study findings.
Just 45% of 276 unselected patients recorded in the metastatic section of the Danish Melanoma Database in 2014 would have been able to participate in five recent phase III clinical trials, the researchers report in the European Journal of Cancer.
“This indicates that the majority of patients diagnosed with active [metastatic melanoma] who are potentially candidates for systemic treatment are not represented in current phase III immunotherapy trials”, they say.
Ineligible patients had a “very poor” prognosis, with a significantly shorter median overall survival (OS) than patients who were eligible for trial participation, at 5.4 versus 18.3 months and a hazard ratio (HR) of 2.44.
The majority (81%) of eligible patients received ipilimumab alone or in combination with another treatment and 43% received pembrolizumab on or after progression, whereas just 25% of ineligible patients received ipilimumab, with 12.5% going onto pembrolizumab on progression.
However, the OS of eligible and ineligible patients who received immunotherapy “appeared similar” at 22.0 versus 12.6 months. And among ineligible patients, those given immunotherapy had significantly longer median OS than those who did not, at 12.6 versus 4.0 months (HR=2.80).
Speaking to medwireNews, lead author Marco Donia, from Copenhagen University Hospital in Herlev, Denmark, explained that this finding is “not entirely unexpected” as the treating physicians had assessed and selected ineligible patients who were likely to benefit from immunotherapy.
But he added: “It is an indirect confirmation that physician’s selection was at least as good as eligibility criteria used in clinical trials.”
At first oncology visit, 29% of the patients were excluded from clinical trial participation on the basis of an ECOG or WHO performance status of 2 or higher, 22% because of active or untreated brain metastases, and 21% because of significant or uncontrolled comorbidity. A further 8.7% were not eligible for trial participation because of other malignancy, while 4.3% had an autoimmune diagnosis and 17% were using immunosuppressive agents.
This left 130 patients, but a further 2.2% were ineligible as they did not have disease measurable using RECIST version 1.1, usually because their lesions were too small.
Donia suggested that while it was perhaps not possible to include patients with and without eligibility criteria features within one trial, “smaller, separate prospective studies should be feasible and, to some extent, are planned/initiated,” such as this phase II study of pembrolizumab in patients with untreated brain metastases.
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