Newly Approved Therapies for Stage III Melanoma Patients

We are in a fortunate time for melanoma patients.  Never have we had effective adjuvant therapy with tolerable toxicity, and perhaps we can reach the milestone of a sharp reduction of stage IV patients.  That would be our wish.  Dr. Richard Joseph, MD of the Mayo Clinic answers your questions on adjuvant therapy below.

1. What does adjuvant mean and what is neoadjuvant?

Adjuvant therapy refers to treatment that occurs after the primary surgery is completed. This could be after a sentinel node biopsy and wide excision. A certain percentage of high-risk patients have a chance of developing a recurrence of melanoma after their surgery. Studies in which the melanoma patients are followed as time passes for recurrence (otherwise known as prospective studies), are now complete. The results demonstrate the benefit of adjuvant therapy in patients with resected (surgically removed) melanoma in decreasing the rate of recurrence. More specifically, there are now four relatively recent studies that have demonstrated benefit in the adjuvant setting including nivolumab, pembrolizumab, ipilimumab, and the combination of dabrafenib and trametinib.

There have also been discussions among melanoma experts about Neoadjuvant therapy. This refers to therapy that occurs before the primary therapy which in the case of melanoma typically means “before surgery”. Multiple studies are trying to determine whether giving systemic therapy prior to surgery can improve outcomes for patients.

2. What stages of melanoma allow for adjuvant therapy?

At present, adjuvant therapy is approved for patients with stage III or stage IV melanoma. Clinical studies are looking in to the utility of adjuvant therapy for patients with stage II melanoma. Within Stage III, I typically recommend adjuvant therapy for Stage IIIB and higher; I typically don’t recommend it for Stage IIIA because the good prognosis for patients with Stage IIIA and these patients were excluded from some of the adjuvant studies.

3. Does adjuvant therapy preclude me from future clinical trials?

All therapy can potentially close future doors for clinical trials but at the same time open other doors. Clinical trials are looking for all sorts of patients with melanoma including those who have been treated in the adjuvant setting in those who have not been treated in the adjuvant setting.

4. Will side effects become permanent, such as thyroid issues, or autoimmune problems?

Certain side effects from immunotherapy are temporary while others can be more permanent. For example some of the common side effects such as fatigue, rash, itching, and diarrhea are usually temporary and resolve once treatment is complete. Other side effects that affect the endocrine system such as the thyroid or adrenal glands tend to be more permanent but very treatable with hormonal replacement.

5. Can the dosage be lowered? Or can I go off the therapy and then back on?

If side effects from immunotherapy occur, we first try to determine the severity of the side effects. If they are relatively minor, we tend to continue the immunotherapy while addressing the side effects with other measures. More significant side effects such as shortness of breath or uncontrollable diarrhea require stopping therapy. Sometimes we can quiet being down the immune system with immune suppressants such as steroids. Once the side effects resolve, it is determined on a case-by-case basis on whether to resume the immunotherapy.

Dr. Richard Joseph, MD, is an assistant professor of medicine/oncology at Mayo Clinic. His Hematology/Oncology fellowship was completed at MD Anderson Cancer Center. He is a voting member of the NCCN (National Comprehensive Cancer Network. He belongs to Melanoma International’s Scientific Advisory Board and received MIF’s Doctor of the Year award for 2015.