GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases
Status:
Completed
Trial end date:
2018-07-31
Target enrollment:
Participant gender:
Summary
Ipilimumab adds a clinical benefit to radiation therapy in patients with melanoma metastatic
to the brain.
Melanoma is the third most common cancer causing brain metastases, after cancers of the lung
and breast, which appears to reflect the relative propensity of melanoma to metastasize to
the central nervous system (CNS). Brain metastases are responsible for 20 to 54 percent of
deaths in patients with melanoma, and among those with documented brain metastases, these
lesions contribute to death in up to 95 percent of cases, with an estimated median overall
survival ranging between 1.8 and 10.5 months, depending upon other prognostic factors.
Ipilimumab is an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) monoclonal antibody that
has demonstrated a clinically relevant and statistically significant improvement in overall
survival, either alone (second line) or in combination with dacarbazine (DTIC) in 1st line.
Ipilimumab has shown activity against brain metastases.
According to the European Medicines Agency (EMA) approved label for Yervoy®, the use of
glucocorticoids at baseline (commonly prescribed when brain metastases are diagnosed) should
be avoided before the administration of ipilimumab. Data show that the use of even high doses
of glucocorticoids for the management of immune-related adverse events do not decrease the
efficacy of Yervoy®. There is no documented experience on the efficacy of Yervoy® when given
concomitantly with radiation therapy and glucocorticoids.
In experimental models, radiation therapy is synergistic to anti-Cytotoxic T-Lymphocyte
Antigen 4 (anti-CTLA4) strategies (abscopal effect).
There are no published results from clinical trials on the interaction between radiation
therapy and ipilimumab.