Melanoma

With 2 different BRAF/MEK combination regimens approved by the FDA, as well as an immunotherapy combination, treatment and sequencing decisions for metastatic BRAF-mutated melanoma can be difficult.

As I write this, the 2016 ASCO conference has just concluded in Chicago. And, as is typical with this event, the amount and level of groundbreaking research and information presented at this year's conference is nothing less than staggering in its scope, innovation, and promise.

Norman E. Sharpless, MD, professor of Medicine and Genetics, chair, the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, UNC School of Medicine, discusses the significance of the ipilimumab/nivolumab findings from the CheckMate-069 trial for melanoma.

For patients with NRAS-mutant melanoma who progress following treatment with an immunotherapy agent, the MEK inhibitor binimetinib offers a promising option.

The purpose of this retrospective study is to evaluate tumor response rates and toxicity profiles of IL-2 therapy in a more contemporary cohort of patients with metastatic melanoma and a history of brain metastases.

Binimetinib, a MEK inhibitor, is seeking FDA approval in the treatment of patients with advanced NRAS-mutant metastatic melanoma.

A variety of dual immunotherapy combination regimens are currently under exploration that could build upon the success seen with the addition of the CTLA-4 inhibitor ipilimumab (Yervoy) to PD-1 blockade with nivolumab (Opdivo) for the treatment of patients with advanced melanoma.

A phase II study is exploring the oncolytic virus talimogene laherparepvec (T-VEC; Imlygic) in the neoadjuvant setting for patients with resectable melanoma.

Therapeutic options have been severely limited for patients with locally advanced or unresectable basal cell carcinoma.

The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) continues to show promise, with recent data demonstrating a 26% improvement in overall survival (OS) with the 2 drugs compared with ipilimumab alone for patients with advanced melanoma.

The National Institute for Health and Care Excellence (NICE) has approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for patients with metastatic melanoma, which allows the combination to be used within the National Health Service (NHS).

Antoni Ribas, MD, PhD, professor of Hematology and Oncology and director of the Tumor Immunology Program Area at UCLA Jonsson Comprehensive Cancer Center, discusses how to appropriately sequence therapies for patients with melanoma.

Choosing between immunotherapy and targeted therapy in the frontline setting for patients with BRAF-mutated melanoma does not have to be a guessing game, according to Keith T. Flaherty, MD.

Although nivolumab (Opdivo) and ipilimumab (Yervoy) are approved in combination for the first-line treatment of patients with metastatic melanoma, regardless of BRAF mutation status, the checkpoint blockade has not automatically become the standard of care in this setting.

A phase Ib expansion cohort of the Keynote-029 trial found that a combined regimen of pembrolizumab (Keytruda) at the standard dose (2 mg/kg) and ipilimumab (Yervoy) at a reduced dose (1 mg/kg) was safe and effective for patients with advanced melanoma.

Keith T. Flaherty, MD, provides an overview of the phase III COMBI-d study, which examined the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) as a treatment of patients with BRAF-mutant metastatic melanoma.

Three-year follow-up data from the phase III COMBI-d study was presented at the 2016 ASCO Annual Meeting, revealing impressive overall survival (OS) and progression-free survival (PFS) data for the dabrafenib (Tafinlar) and trametinib (Mekinist) combination therapy for patients with BRAF-mutant metastatic melanoma.

Patients with BRAF-mutant melanoma obtained no survival benefit from combined treatment of anti-BRAF therapy and an immune checkpoint inhibitor, a retrospective analysis showed.

Discontinuing nivolumab-ipilimumab treatment because of adverse events did not have a detrimental effect on survival among patients with advanced melanoma, follow-up from a randomized trial showed.

Contrary to investigators' expectations, an observational study found that obesity is associated with increased progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma who were treated with a combination of dabrafenib (Tafinlar) and trametinib (Mekinist). These results were presented at the 2016 ASCO Annual Meeting.

In a phase Ib study, combining talimogene laherparepvec (T-VEC), an oncolytic virus, with pembrolizumab at full doses had an acceptable safety profile, with evidence of clinical benefit in patients with advanced melanoma.

The phase I KEYNOTE-022 study, which tested pembrolizumab (Keytruda) in combination with dabrafenib (Tafinlar) and trametinib (Mekinist) for BRAF-mutant advanced melanoma, has shown a manageable toxicity profile in patients with BRAF V600-mutant melanoma.

Baseline LDH levels, ECOG performance status, and presence/absence of liver metastasis are clinical characteristics associated with favorable progression-free survival (PFS) in BRAF V600-mutated melanoma patients receiving vemurafenib (Zelboraf) monotherapy or combination cobimetinib (Cotellic) plus vemurafenib, according to an analysis presented at the ASCO 2016 Annual Meeting.

An ongoing phase IIa basket study is evaluating treating patients who have molecular abnormalities with agents that target the HER2, BRAF, Hedgehog, or EGFR pathways, regardless of the patient's tumor type and the drug's original indication.

Combination therapy nivolumab (Opdivo) and ipilimumab (Yervoy) resulted in reduced disease progression risk of 58% when compared with ipilimumab alone in patients with advanced melanoma. Additionally, nivolumab monotherapy showed greater risk reduction (45%) compared with ipilimumab single-agent treatment.