Jason J. Luke, MD, FACP, an associate professor of medicine in the Division of Hematology/Oncology and director of the Cancer Immunotherapeutics Center Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center Hillman Cancer Center, compares predictive and prognostic biomarkers in melanoma.

The concept of biomarkers is important in all areas of oncology, but is especially relevant in the field of melanoma, explains Luke. Prognostic biomarkers can indicate how well a patient is going to do over time, whereas predictive biomarkers are commonly linked to an available therapeutic approach, Luke says.

In some cases, biomarkers can be prognostic and predictive, Luke explains. For example, in melanoma, 

 mutations indicate poor prognosis but are also predictive of the treatment effect of a BRAF inhibitor, says Luke. Conversely, in lung cancer, 

 mutations predict better prognosis and suggest that a patient is likely to respond to an EGFR inhibitor. It’s important to understand these differences in biomarkers so that patients may derive the optimal benefit from more individualized therapy, Luke concludes. 

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Jason J. Luke, MD, FACP, compares predictive and prognostic biomarkers in melanoma. 

Dr. Luke on Predictive Versus Prognostic Biomarkers in Melanoma  

Jason J. Luke, MD, FACP, an associate professor of medicine in the Division of Hematology/Oncology and director of the Cancer Immunotherapeutics Center Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center Hillman Cancer Center, discusses the role of molecular testing in melanoma.

Molecular testing should be incorporated into standard practice to help guide therapeutic options in oncology, says Luke. However, evidence from phase 3 clinical trials should not be discounted, pending molecular testing results. Moreover, molecular testing can offer potential solutions to situations where standard treatment options are not conclusive, Luke explains. 

In melanoma, next-generation sequencing does not have to be ordered up front for all patients, says Luke. Instead, ordering molecular testing in patients who don’t have 

 mutations may help to identify rare mutational variants, such as 

 amplifications, for which therapeutic options are available, concludes Luke.

Jason J. Luke, MD, FACP, discusses the role of molecular testing in melanoma.  



Dr. Luke the Role of Molecular Testing in Melanoma 

Jason J. Luke, MD, FACP, an associate professor of medicine in the Division of Hematology/Oncology and director of the Cancer Immunotherapeutics Center Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center Hillman Cancer Center, discusses the role of targeted therapy in melanoma.

Genomic profiling can help to inform the optimal treatment strategy for a patient with metastatic melanoma, Luke says. 

 mutations are present in about 50% of all patients with melanoma, Luke explains. Additionally, about 25% and 15% of patients harbor a 

 mutation, respectively. Patients with can also harbor 

 amplifications, or other rarer genetic aberrations, explains Luke. 

 mutations are the only targetable alteration per an FDA-approved therapy, Luke says. However, ongoing research efforts are developing therapies to target 

 mutations in patients with acral or mucosal melanoma, as well as 

Other clinical trials are evaluating MET and ERK inhibitors alone or in combination with CDK inhibitors in patients with 

Jason J. Luke, MD, FACP, discusses the role of targeted therapy in melanoma.  



Dr. Luke on the Role of Targeted Therapy in Melanoma 

Jason J. Luke, MD, FACP, an associate professor of medicine in the Division of Hematology/Oncology and director of the Cancer Immunotherapeutics Center Immunology and Immunotherapy Program at the University of Pittsburgh Medical Center Hillman Cancer Center, discusses the importance of BRAF in melanoma.

, found in half of all patients with melanoma, is a foundational mutation that was 1 of the seminal targets for early targeted agents, says Luke. 

 mutations also have to occur in conjunction with other mutations or dysregulations of the tumor. 

In melanoma, half of the treatment paradigm is targeting 

 3 different FDA-approved BRAF/MEK inhibitor combinations. Now, BRAF/MEL inhibitors are even being combined with PD-1 antibodies, Luke adds.

 is very important biologically, as it drives the development of about half of the melanoma cases, says Luke; it is almost important therapeutically, as it is integrated into the treatment paradigm for half of patients with the disease and dictates how treatments are selected and sequenced, concludes Luke.

Jason J. Luke, MD, FACP, discusses the importance of BRAF in melanoma.

Dr. Luke on the Importance of BRAF in Melanoma

Jason Luke, MD, assistant professor of medicine at the University of Chicago Medicine, discusses the clinical trial landscape for melanoma.

According to Luke, the clinical trial landscape is split in 2 areas of focus. Registrational phase III trials are looking at more robust combinations that could impact the field right away. And then there is the developmental space, which is investigating what molecules are going to be the next generation of things to look for.

There is preliminary data inhibiting a molecule called LAG3, which is a T cell checkpoint that could rescue patients who have become refractory to PD-1 blockade.

Jason Luke, MD, assistant professor of medicine at the University of Chicago Medicine, discusses the clinical trial landscape for melanoma

Dr. Luke on the Clinical Trial Landscape for Melanoma

Jason Luke, MD, assistant professor of medicine at the University of Chicago Medicine, discusses the future of immunotherapy combinations for patients with melanoma. 

The future of systemic therapy for patients with melanoma in the advanced stages is in combinations, explains Luke. Currently, the standard of care for many patients is PD-1 antibodies, but combinations will continue to show improvement.  

Combinations are also showing improvement in the adjuvant setting. In the next 2 to 5 years, most patients will be receiving combinations, states Luke.  

Jason Luke, MD, assistant professor of medicine at the University of Chicago Medicine, discusses the future of immunotherapy combinations for patients with melanoma.

Dr. Luke on the Future Role of Immunotherapy Combinations in Melanoma

Jason Luke, MD, assistant professor of medicine at the University of Chicago Medicine, discusses the combination of pembrolizumab (Keytruda) and talimogene laherparepvec (T-VEC; Imlygic) for the treatment of patients with melanoma.

A combination that is of a lot of interest is a PD-1 antibody and an oncolytic virus, states Luke. There are drugs that are approved for each as a monotherapy, but the combination of pembrolizumab and T-VEC has the potential to be promising.

T-VEC is a modified virus that is injected into melanoma tumors that are on the skin.  

Dr. Luke on the Combination of Pembrolizumab and T-VEC for Melanoma

Jason Luke, MD, assistant professor of medicine, University of Chicago Medicine, discusses the combination approach of a PD-1 antibody plus an IDO inhibitor for patients with melanoma.

There are early-phase data with pembrolizumab (Keytruda) and epacadostat showing that adding the IDO inhibitor improved the response rate to pembrolizumab monotherapy from 40% to 55%, explains Luke. There was no increased toxicity observed in this combination.

A phase III trial investigating this combination compared with a placebo-controlled pembrolizumab monotherapy has completed accrual. According to Luke, this combination could change the standard of care for patients with melanoma.

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Dr. Luke Discusses PD-1 Plus IDO Inhibitors in Melanoma

Jason Luke, MD, an assistant professor of medicine at the University of Chicago Medicine, discusses impactful data in the field of melanoma.

According to Luke, the most impactful data are in the setting of adjuvant therapy after surgery. The BRIM8 trial is investigating vemurafenib (Zelboraf) versus placebo, the COMBI-AD study is investigating dabrafenib (Tafinlar) and trametinib (Mekinist) versus placebo, and the CheckMate-238 study is investigating nivolumab (Opdivo) versus ipilimumab (Yervoy).

All of these data sets are reading out as positive and showing improvements in relapse-free survival. Longer follow-up in terms of overall survival are still needed.

Dr. Luke on Impactful Data in the Field of Melanoma

Jason Luke, MD, an assistant professor of Medicine at the University of Chicago Medicine, discusses some of the challenges that oncologists may face when administering immunotherapy agents to patients with melanoma.

According to Luke, there can sometimes be a bit of a learning curve for physicians if they are not that familiar with treating their patients with immunotherapy. One important concern to keep in mind is the possibility of pseudo-progression or delayed response. Though it is relatively rare, this phenomenon has been reported in about 10% to 15% of patients with melanoma, says Luke. His advice is to simply treat the patient for whatever they are presenting with. For example, if a patient comes in and feels well, and there is no evidence of biochemical decline, but a scan reveals progression, the possiblity of delayed response should be considered before taking any other action.

Another unique challenge with immunotherapy is the evaluation of toxicity. Many oncologists are used to side effects of chemotherapy, such as hair loss, fatigue, etc. Patients treated with immunotherapy, on the other hand, experience more autoimmune-like side effects, like colitis, pneumonitis, as well as endocrinological problems such as thyroiditis.

Jason Luke, MD

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