Adjuvant treatment is used in addition to tumor removal e.g. via surgery or radiotherapy to help delay or prevent the recurrence of melanoma. It is often recommended for high-risk melanoma (defined as melanoma deeper or thicker than 4mm thick at the primary site or involves nearby lymph nodes). Approved adjuvant therapies in melanoma include interferon and, more recently, ipilimumab. But neither of these approaches is wholly satisfying since relatively few patients appear to benefit and side-effects are a major factor.

Adjuvant Therapy (NCI Cancer Dictionary: (A-joo-vunt THAYR-uh-pee) Additional cancer treatment given after the primary treatment (or surgery) to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, immunotherapy or biological therapy.

But new treatment options may be on the horizon. At the European Society for Medical Oncology (ESMO) Congress held in Madrid, Spain September 8 – 12, two studies reported that already-available drugs may offer greater benefit to patients and add more choices to the adjuvant therapy arsenal.

One study, COMBI-AD, evaluated 12 months of treatment with the combination of targeted agents dabrafenib and trametinib vs no treatment in Stage 3 patients with BRAF-mutant melanoma. The results were presented at the meeting and published concurrently in the prestigious New England Journal of Medicine (NEJM). At 3-years of follow-up, 58% of treated patients had not had recurrent disease compared to 39% in the control group and 86% of patients were alive vs 77% in the control group. Overall, 26% of patients discontinued treatment because of side-effects. 

“The results of COMBI-AD actually exceeded my personal expectations,” said Dr. Axel Hauschild, MD, Professor of Dermatology at the University of Kiel in Germany. “All stages of stage III disease benefited the same.”  

In a second adjuvant trial reported at ESMO and also published in NEJM, the CheckMate-238 study evaluated treatment with nivolumab compared to ipilimumab. With data reported at the 12-month mark, 70.5% of nivolumab treated patients had not recurred compared to 60.8% of patients in the ipilimumab-treated group. Only 9.7% of nivolumab patients discontinued treatment because of side-effects compared to 42.6% of patients treated with ipilimumab. 

According to Jeffrey Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center, NYU Langone Health: “Nivolumab [compared to ipilimumab] looks like a superior adjuvant melanoma regimen, from every angle,” he concluded.  

Results seen in these two studies are very encouraging. In fact, the results have been called ‘practice-changing’ by some experts and if adopted into treatment guidelines and/or approved by FDA, will be within reach of more and more patients. If moved into the treatment standard of care, doctors and their patients will need to decide which adjuvant approach is preferable for them from among interferon, ipilimumab, nivolumab, and dabrafenib/trametinib for BRAF mutant melanoma. More research is needed to provide the information to guide such a choice scientifically. But for the near future, the fact that choices exist will be a ‘good problem to have.’ 

What is Adjuvant Therapy?