Combining Novel Drugs and Using Surgery at Key Moments Defines Modern Melanoma Treatment

Patients with melanoma have reaped the benefits of surgical strategies, targeted drugs and immunotherapies, and their options continue to expand as more medicines and drug combinations enter the marketplace and surgery is applied in new ways.

Targeted drugs are used as first or second-line treatments and provide a survival advantage to patients, even sparking responses in those with disease that has spread to their brains, said Dr. Omid Hamid.

To build on that success, he said, investigators are examining the use of these therapies in combination regimens that pair them with immunotherapies known as checkpoint inhibitors, which rev up the immune system by interfering with the activity of certain proteins. Health outcomes can also be improved by employing surgery at various milestone moments during the course of the disease.

In an interview with OncLive^®, a sister publication of CURE^®, Hamid, director of the Melanoma Center and phase 1 immuno-oncology program at The Angeles Clinic and Research Institute, discussed emerging treatment approaches, the role of surgery and ongoing research efforts in melanoma.

OncLive: What role does targeted therapy play in the modern management of patients with melanoma?

Hamid: There is now the idea that some immune activity exists with targeted therapies and (there is an) ability to have a tolerable triplet regimen with immunotherapy and targeted therapy. Future efforts will be dedicated to understanding the benefits we can get with this triplet therapy.

Multiple randomized trials are nearing completion and initial data show a progression-free survival benefit (a longer time until disease progression). For example, the (IMspire150) TRILOGY study of cobimetinib (Cotellic), vemurafenib (Zelboraf) and atezolizumab (Tecentriq) versus cobimetinib and vemurafenib alone has been shown to have a progression-free survival advantage. Other triplets are being investigated in ongoing research efforts.

Despite the emergence of these targeted therapies in recent years, does surgery still have a role in this space?

Absolutely. Surgery is going to help us with predictive and prognostic markers. The tissue (harvested) will help us in the (presurgical) and metastatic settings to figure out what a response really means.

In my practice, I have the pleasure of working with Dr. Mark B. Faries, of The Angeles Clinic and Research Institute, who is a leader in melanoma surgical and (postsurgical) therapy. Through his work in the MSLT-II trial, we've learned that we don't need to (remove the lymph nodes). That’s an important thing for our patients in terms of (avoiding side effects) and it also allows us to move further with (postsurgical) therapy in a more rapid fashion. Additionally, (there’s a role for metastasectomy in those with) progressive disease. This refers to the removal of cancerous tissue in the patient who is either responding except for one area, or who is responding and then progresses in an area where we can surgically remove that tumor and allow future therapy.

In addition, for immunotherapy, it’s important to remember that you need time for an immune response to happen. We have certain patients who have obstructions or areas that are troublesome and don't allow us to get that dose intensity. In these cases, our surgical colleagues can come in, take that area out and allow us to treat those patients until they achieve a response.

What immunotherapies are showing promise?

Obviously, our checkpoint inhibitors are showing significant benefit and long-term survival. Combinations are showing five-year survival (rates) of over 50%. We are understanding dosing and flip dosing in a better fashion, but the next frontier in melanoma is combination regimens that are more tolerable, with less … toxicity. We are also waiting to see what trials examining vaccine approaches and oncolytic therapies will show. (Checkpoint inhibitors that target different proteins) may also have less toxicity. All these regimens are not just in the first-line setting, but also for patients with (recurrent) disease.

In addition, we're now looking (at immunotherapies that use a patient’s own immune cells, multiplied and in some cases engineered to recognize cancer). In melanoma, CAR (chimeric antigen receptor) T-cell studies are opening (that will evaluate) benefits for solid tumors. Adoptive T cell therapy is also becoming more and more available.

Combinations of those therapies are (being evaluated) in clinical trials. For example, one clinical trial is now (examining a type of adoptive T cell therapy called) tumor-infiltrating lymphocyte therapy (paired with checkpoint) inhibition for multiple solid tumors. The ability to take those regimens and utilize them in the frontline and in patients with (treatment-resistant) disease is going to be key.

The original article appeared on OncLive^®, titled “Novel Therapies Expand Options in Melanoma, But Surgery Retains Role.”