ASCO Melanoma Spotlight

Paola A. Ascierto, MD, medical oncologist, director of Melanoma Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori &ldquo;Fondazione G. Pascal,&rdquo; discusses results of a phase Ib/II dose-escalation study evaluating triple combination therapy with encorafenib, binimetiinib, and ribociclib (Kisquali) in patients with <em>BRAF V600</em> solid tumors and melanoma.

More than half of patients with immunotherapy-relapsed/refractory melanoma benefited from treatment with nivolumab and an anti-lymphocyte activation gene-3 (LAG-3) antibody, according to data from an early clinical study.

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.&nbsp;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;

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.

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.

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.

Marc Ernstoff, MD, director of melanoma, Cleveland Clinic, discusses progression-free survival (PFS) and safety in patients with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI).

Keith T. Flaherty, MD, Harvard Medical School and Center for Targeted Therapies at Massachusetts General Hospital, spoke to Targeted Oncology about the importance of combination BRAF/MEK inhibitors in the treatment of melanoma.

Janice M. Mehnert, MD, of the Rutgers Cancer Institute of New Jersey, gave a presentation at the 2015 ASCO Annual Meeting entitled, “Should Comorbidities Be an Automatic Exclusion for Clinical Trials?”

At the ASCO 2015 Annual Meeting, F. Stephen Hodi, MD presented an analysis of the phase II CheckMate 069 trial covering objective response rate, progression-free survival, and safety in predefined subgroups, including those with poor prognostic factors.

Results presented at the 2015 ASCO Annual Meeting by Antoni Ribas, MD, PhD, examined the feasibility of combining these immunotherapy and targeted therapies in a phase I study.

Stefani Spranger, PhD, post-doctoral fellow, Department of Pathology, The University of Chicago Medicine, discusses the significance of melanoma intrinsic β-catenin signaling on immune exclusion and resistance to immunotherapies.

At the 2015 ASCO Annual Meeting, Adil I. Daud, MD, UCSF Hellen Diller Family Comprehensive Cancer Center, presented a pooled analysis of 655 patients with advanced melanoma enrolled in the KEYNOTE-001 trial.

Dr. Larkin presented updated results from coBRIM, including progression-free survival, response rate, and treatment outcomes of patients who harbored additional oncogenic mutations in their pretreatment tumor samples at the 2015 ASCO Annual Meeting.

Current trends and recent advances have reinforced the superiority of combined inhibition of BRAF/MEK in melanoma treatment, according to Michael A. Davies, MD, during a summary of studies in melanoma.