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.

Pooled analysis, presented at the 2016 ASCO Annual Meeting, showed the safety profile of dabrafenib and trametinib is consistent with reports from three individual studies.

Treatment with dabrafenib (Tafinlar) plus trametinib (Mekinist) resulted in a complete response in 9 of 19 patients with stage IIIb/c BRAF V600 melanoma, according to results from a phase II trial presented at the 2016 ASCO Annual Meeting.

Three years after the pembrolizumab (Keytruda) clinical trial for advanced melanoma that led to the drug's FDA approval, 40% of the patients are still alive.

With expanding availability of effective single-agent and combination immunotherapies and combination BRAF/MEK inhibitor regimens, all of which have been shown to improve survival and reduce risk of progression, the optimal sequencing of therapies has become increasingly complex.

A number of new combination approaches have gained approval in the past year for the treatment of patients with BRAF-mutant metastatic melanoma, expanding the number of effective treatment options that can improve quality and length of life for many patients.

With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes.

BRAF mutation testing has become an essential tool in the diagnostic workup and management of patients with advanced melanoma.

Hedgehog inhibitors have revolutionized the treatment paradigm for patients with advanced basal cell carcinoma, says Desiree Ratner, MD.

Toni Ribas, MD, discusses the significance of the CheckMate-069 data and where the field of immunotherapy in melanoma is headed.

By working together, the potential for clinical benefit in patients with cancer is increasingly bright.

Single-agent nivolumab (Opdivo) demonstrated a robust 5-year overall survival (OS) rate of 34% for heavily pretreated patients with metastatic melanoma who had not received prior ipilimumab (Yervoy), according to long-term findings from a single-arm phase I study.

Immunotherapy should be considered along with VEGF and mTOR TKIs as a highly effective treatment modality for patients with metastatic renal cell carcinoma (RCC).

PD-1/PD-L1 should be the backbone of melanoma treatment for many patients, says Jason Luke, MD, an assistant professor of Medicine at the University of Chicago Medicine.