Ipilimumab for Initial Treatment of Metastatic Uveal Melanoma

Conference Correspondent - ASCO 2014 - Immuno-Oncology

Uveal melanoma is the most common primary intraocular malignancy in adults. In the United States, approximately 4.3 new cases are diagnosed per 1 million people, with no variation based on geographic latitude.1 Uveal melanoma is typically identified in older individuals; the rate of new cases peaks near 70 years of age.2 Patients with extraocular extension of uveal melanoma and distant metastasis have an extremely poor prognosis.3 The Ocular Melanoma Foundation estimates median survival of 2 to 8 months.4

Because no therapies are approved for use in metastatic uveal melanoma (MUM), treatment remains unstandardized. In addition to surgical resection and treatments directed to liver metastases, options for systemic therapy include dacarbazine, temozolomide, taxanes, and platinum agents.4 Studies of ipilimumab (IPI), an anti-CTLA-4 antibody, have demonstrated durable responses and improved overall survival (OS) in patients with advanced cutaneous melanoma.5 However, patients with MUM were excluded from enrollment in these trials.

To learn if IPI is active in MUM, Piulats and colleagues conducted a study of single-agent IPI in newly diagnosed adult patients with MUM (ASCO 2014; Abstract 9033). Known as the GEM-1 or EudraCT 2010-024415-14 trial, this effort was an open-label, single-arm, phase 2 trial. The study was conducted in 5 centers affiliated with the Spanish Melanoma Group (GEM). Eligible patients had progressive metastatic disease, good performance status (ECOG PS 0 or 1), and no prior systemic treatment for MUM. Treatment consisted of IPI dosed at 10 mg/kg every 3 weeks for 4 doses (induction) followed by dosing every 12 weeks as maintenance until progression, intolerance, or study withdrawal. Efficacy endpoints included OS, progression-free survival (PFS), overall response rate, and safety using immune response criteria.

Of the 32 patients enrolled, 1 patient was ineligible due to the absence of metastatic disease at baseline. Eighteen of these patients with MUM were men, and the mean age was 60 years. Progressive liver metastases were present at baseline in 25 patients (81%), and were frequently multiple and affecting both lobes.

Grade 3 adverse events (AEs) in this study included elevated liver enzymes, hypophysitis, fatigue, vomiting, urinary tract infection, anorexia, diarrhea, and suprarenal insufficiency. Grade 4 toxicities included elevated liver enzymes and increased uric acid.

The response rate evaluation shows a relatively low overall response of 7% using both modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC). However, disease control rates were 39% and 46% using the 2 criteria, respectively. Response rate data are summarized in the Table.

Table: Response Rate of IPI in Patients with MUM (n = 31)

Response mWHO
N (%)
N (%)
Complete Response 0 0
Partial Response 2 (7) 2 (7)
Stable Disease 10 (32) 13 (39)
Progressive Disease 13 (42) 10 (32)
Not Evaluable 6 (19) 6 (19)

The researchers reported median OS of 9.8 months, as well as 6-month PFS of 27% and 12-month PFS of 19%. This first clinical trial of IPI in patients with MUM suggests efficacy and acceptable tolerability. In this poor-prognosis condition for which there is no standard of care, use of immunotherapy warrants further study.


  1. National Cancer Institute website. Intraocular (Uveal) Melanoma Treatment: PDQ®. General Information About Intraocular (Uveal) Melanoma Treatment. Last modified: April 11, 2014. www.cancer.gov/cancertopics/pdq/treatment/intraocularmelanoma/HealthProfessional/page1#Reference1.3. Accessed June 2, 2014.
  2. Singh AD, Bergman L, Seregard S. Uveal melanoma: epidemiologic aspects. Ophthalmol Clin North Am. 2005;18(1):75-84.
  3. Gragoudas ES, Egan KM, Seddon JM, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1999;98(3):383-389;discussion 390.
  4. Ocular Melanoma Foundation website. Treatment of Metastatic Disease. www.ocularmelanoma.org/metstreatment.htm. Accessed June 2, 2014.
  5. Yervoy (ipilimumab) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; December 2013.