A Danish study reported in the European Journal of Cancer by Marco Donia, MD, PhD, of the Center for Cancer Immune Therapy, Herlev Hospital, Denmark, and colleagues indicates that more than half of patients with metastatic melanoma do not satisfy requirements for enrollment in phase III trials of immune checkpoint inhibitors.
The study involved 276 unselected cases (excluding those with ocular melanoma) from the Danish MM (metastatic melanoma) Database referred for first oncologic evaluation in 2014. The proportion of patients meeting seven predefined exclusion criteria in five recent phase III immunotherapy trials was analyzed. The criteria consisted of the following: Eastern Cooperative Oncology Group/World Health Organization performance status ≥ 2; active brain metastases or leptomeningeal metastases; any serious or uncontrolled medical conditions; autoimmune diseases; previous malignancies; receipt of immunosuppressive medications; and not having measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
More Than Half of Patients ‘Not Eligible’
At first visit, a total of 152 patients (55%) did not meet inclusion criteria for 1 or more reasons; 29% had a performance status ≥ 2, 22% had active/untreated known brain metastases, 21% had significant comorbidities, 9% had other malignancies, 4% had autoimmune diseases, 17% were receiving immunosuppressant drugs, and 2% did not have measurable disease.
In the “eligible group,” 81% of patients received ipilimumab (Yervoy) as monotherapy or in a clinical trial in combination with indoleamine 2,3-dioxygenase vaccination and 43% received pembrolizumab (Keytruda) after disease progression on or after ipilimumab. In the “not eligible” group, 25% received ipilimumab and 12.5% received pembrolizumab after disease progression on or after ipilimumab.
Median overall survival in the entire population was 7.9 months, including 5.4 months in the not eligible group vs 18.3 months in the eligible group (hazard ratio [HR] = 2.44, P < .0001). Median overall survival among patients receiving immunotherapy was 12.6 months for not eligible patients vs 22.0 months for eligible patients (HR = 1.08, P = .78). In the not eligible group, those who did not receive immunotherapy had a median survival of 4 months (HR = 2.80, P < .001, vs those receiving immunotherapy).
The investigators concluded: “We found that most patients diagnosed with [metastatic melanoma] would not even be considered for screening to enrolment in an immunotherapy clinical trial with classical eligibility criteria. This indicates that a majority of patients…is not represented in registration trials, and thus results from these trials do not necessarily apply to real-world [metastatic melanoma] patients.” ■
Donia M, et al: Eur J Cancer 74:89-95, 2017.