Melanoma

Dabrafenib (Tafinlar) plus trametinib (Mekinist) achieved an intracranial response (IR) rate of 58% in melanoma that has metastasized to the brain. The median duration of overall response (OR) of 6.5 months was generally shorter than that observed in melanoma patients without brain metastases. These initial findings from the phase II COMBI-MB trial were presented during an oral abstract session at the 2017 ASCO Annual Meeting.

Nivolumab (Opdivo) plus ipilimumab (Yervoy) or ipilimumab alone are associated with a high incidence of gastrointestinal (GI) toxicity, but most adverse events (AEs) are effectively managed using immunomodulators, which do not appear to inhibit tumor response. Additionally, nivolumab plus ipilimumab significantly improved overall survival (OS) and objective response rate (ORR) versus ipilimumab alone in patients with untreated advanced melanoma.

Overall survival in advanced melanoma treated with targeted therapy had a strong association with high PD-L1 expression and high levels of tumor infiltrating lymphocytes, analysis of tissue specimens from a randomized trial showed.

Neoadjuvant and adjuvant dabrafenib (Tafinlar) plus trametinib (Mekinist) increased the overall response rate (ORR) to 85% in patients with high-risk resectable <em>BRAF</em>-mutant metastatic melanoma. And interestingly, the pathologic complete response (pCR) rate with the combination was 58%, as demonstrated in findings presented during the 2017 ASCO Annual Meeting.

A 3-drug regimen for advanced melanoma led to objective responses in a majority of patients with advanced <em>BRAF</em>-mutant disease but also proved to be somewhat toxic, a small phase II study showed.

Georgina V. Long, BSc, PhD, MBBS,&nbsp;professor of medical melanoma oncology, Melanoma Institute Australia, discusses 5-year overall survival data from a phase II trial of dabrafenib (Tafinlar) and trametinib (Mekinist) in patients with <em>BRAF V600</em>-mutant unresectable or metastatic melanoma during the 2017 ASCO Annual Meeting.

Combining the PD-1 inhibitor pembrolizumab (Keytruda) with the HDAC inhibitor entinostat demonstrated promising clinical activity and acceptable safety in patients with melanoma who were refractory to immune checkpoint inhibitors.&nbsp;

Charles M. Rudin, MD, PhD, chief, thoracic oncology, Memorial Sloan Kettering Cancer, discusses a study of intravenously delivered coxsackievirus A21 with pembrolizumab to treat patients with advanced cancers.

The Therapeutic Approach for Malignant Melanoma

The Therapeutic Approach for Malignant Melanoma

Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, discusses a phase 1/1b first in-human study of IPI-549, a PI3K gamma inhibitor as monotherapy and in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors.

Howard L. Kaufman, MD, a surgical oncologist at Rutgers Cancer Institute of New Jersey, discusses a study which showed further durable responses to avelumab (Bavencio) in patients with merkel cell carcinoma who progressed after chemotherapy.

Outcomes have significantly improved for patients with melanoma in the wake of newer targeted treatments. Yet, brain metastases from melanoma remain a significant unmet need, with up to 60% of patients with advanced melanoma developing brain metastases.

Treatment of Malignant Melanoma