The use of pembrolizumab for the treatment of metastatic uveal melanoma.

Kottschade, Lisa A.; McWilliams, Robert R.; Markovic, Svetomir; Block, Matthew S.; Bisneto, Jose Villasboas; Pham, Anthony Q.; Dronca, Roxana S.

doi:10.1200/jco.2015.33.15_suppl.9010

Cited by 20 publications

(19 citation statements)

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“…[21][22][23] Objective tumor responses in patients with uveal melanoma who received treatment with PD-1 antibodies were reported previously in a small case series of 7 patients. 26 The data reported here confirm that PD-1 and PD-L1 antibodies can confer clinical benefits in patients with uveal melanoma (clinical benefit was observed in 7 of 56 patients; clinical benefit rate, 12.5%), but these responses were rare; in our experience, durable partial responses were observed in only 3.6% of patients. Furthermore, the median PFS (2.6 months) and OS (7.7 months) also were modest, demonstrating that major therapeutic benefits of PD-1/PD-L1 antibody therapy are limited to a small subset of patients.…”

Section: Discussionsupporting

confidence: 79%

“…A recent case series described 2 objective responses in patients with metastatic uveal melanoma who received pembrolizumab as part of an expanded ac-cess study. 26 To investigate this further, we report clinical outcomes in a larger series of 56 patients who received treatment at 9 institutions with PD-1 (pembrolizumab or nivolumab) or PD-L1 (atezolizumab) antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies

Algazi

Tsai

Shoushtari

et al. 2016

Cancer

314

264

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BACKGROUND Antibodies inhibiting the programmed death receptor 1 (PD-1) have shown significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized. METHODS 58 stage IV uveal melanoma patients received PD-1 or PD-L1 antibodies between 2009 and 2015 at nine academic centers. Patients who were evaluable for response were eligible for analysis. Imaging was performed every 12-weeks and at the investigators’ discretion. Safety and clinical efficacy outcomes including best overall response (BOR), progression-free survival (PFS), overall survival (OS) were determined retrospectively. RESULTS Of 56 eligible patients, 48 (86%) had received prior therapy and 35 (63%) had been treated with ipilimumab. Three patients had an objective response to ipilimumab and 8 patients had stable disease as the best response. 38 (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in two patients for an overall response rate of 3.6% (95% CI 1.8-22.5%). Stable disease (≥ 6 months) was observed in 5 (9%) patients. The median PFS was 2.6 months (95% CI 2.4-2.8 months) and the median OS was 7.6 months (95% CI 0.7-14.6 months). There was no association between prior treatment with ipilimumab or liver directed therapy and PFS or OS. Treatment was well tolerated and only 1 patient discontinued treatment due to toxicity. CONCLUSIONS PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies

Algazi

Tsai

Shoushtari

et al. 2016

Cancer

314

264

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“…In a single-center EAP, 7 patients with metastatic uveal melanoma received 2 mg/kg of pembrolizumab every 3 weeks. 95 Two patients had objective responses (1 complete response and 1 partial response), and the median PFS was 12.2 weeks in that report.…”

Section: Immunotherapymentioning

confidence: 77%

Uveal melanoma: From diagnosis to treatment and the science in between

Chattopadhyay

Kim

Gombos

et al. 2016

Cancer

310

258

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Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-312. V C 2016 American Cancer Society.KEYWORDS: breast cancer 1-associated protein 1 (BAP1), choroidal melanoma, diagnosis, guanine nucleotide binding protein a11 (GNA11), guanine nucleotide-binding protein Q polypeptide (GNAQ), ocular melanoma, review, science, treatment, uveal melanoma. BACKGROUND AND EPIDEMIOLOGYUveal melanoma is the most common primary intraocular malignancy. The uveal tract is the pigmented layer of the globe encompassing the iris, ciliary body, and choroid (Fig. 1). The terms choroidal melanoma and ocular melanoma are alternative terms for this cancer, because most of the uveal tract is choroidal. However, the term ocular melanoma should be avoided, because it implies the inclusion of conjunctival and adnexal melanomas, which behave and are managed like cutaneous rather than uveal primaries. Approximately 1500 new cases of uveal melanoma are diagnosed in the United States each year, most commonly arising in the choroid followed by the ciliary body. Iris melanomas are the least common location for uveal melanoma (Fig. 2).1 Although the disease has no sex preference, it is more common in middle-aged Caucasians (median age at presentation, 58 years). Risk factors include the presence of a choroidal nevus, which can be observed in 7% to 8% of the Caucasian population. Certain skin conditions, such as dysplastic nevus syndrome and nevus of Ota, are also associated with uveal melanoma.2 It has been theorized by some investigators that exposure to ultraviolet radiation increases the risk of this neoplasia, but this has not been definitively proven. Whereas certain somatic mutations are associated with neoplastic growth and distant metastasis, the malignancy is not inherited in a traditional genetic fashion, although it is believed that individuals who have germline breast cancer 1 (BRCA1)-associated protein 1 (BAP1) mutations are at higher risk for uveal and cutaneous melanoma as well as mesothelioma and renal cancers.

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“…with the PD-1 antibody pembrolizumab. 101 In this case, a higher median PFS was obtained (4 months). In this study, however, patients had previously shown to response to ipilimumab.…”

Section: Immunotherapymentioning

confidence: 69%

Recent advances in uveal melanoma treatment

Álvarez‐Rodríguez

Latorre

Posch

et al. 2017

Medicinal Research Reviews

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care.In this article we provide a comprehensive overview of the molecular framework of UM, highlighting the most common mutations involved in this kind of cancer. It also covers the most recent treatments from basic research to clinical trials, including small molecules, nucleic acids or immunotherapy, among others. It is intended to serve as a key reference for clinicians and researchers working in this field.

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The use of pembrolizumab for the treatment of metastatic uveal melanoma.

Cited by 20 publications

References 0 publications

Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies

Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies

Uveal melanoma: From diagnosis to treatment and the science in between

Recent advances in uveal melanoma treatment

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