Even though the incidence of malignant melanoma is increasing, the majority of cases are diagnosed at an early stage. In this setting, surgery is the best option, proving to be curative in the majority of times. Early diagnosed patients who are at high-risk of developing metastatic stage III melanoma can benefit from additional adjuvant therapy, a recent topic of discussion in a forum of oncologists, posted on the OncLive website.
Jeffrey A. Sosman, MD, Vanderbilt-Ingram Cancer Center, Nashville, began by noting that currently, standard adjuvant therapies for patients suffering with an advanced form of the disease include interferon alpha-2b and peg interferon alpha-2b, both evaluated in clinical studies that showed strong evidence for improved recurrence-free survival, alongside minor data suggesting they also improve overall survival.
Alternatively, BRAF (MAP kinase inhibitor) therapies either alone or in combination with MEK inhibitors directed at high-risk melanoma patients who have BRAF mutations, also have an important role when administered in the right patient population.
Clinical trials exploring the potential of immune checkpoint inhibitors, such as those targeting CTLA-4 with ipilimumab or PD-1 with nivolumab, are currently being developed.
For example, the ongoing multi center Phase III E1609 study is currently comparing the effect of postoperative adjuvant ipilimumab at either 10 mg/kg or 3 mg/kg with that of high-dose interferon α-2b on recurrence-free and overall survival in patients with high-risk stage III or IV melanoma.
Additionally, recent data from the phase III EORTC 18701 clinical trial has shown that ipilimumab administered at 10 mg/kg and used as an adjuvant in stage III node-positive melanoma patients, can reduce cancer recurrence (46.5%) when compared to placebo (34.8%), at a median follow-up of 2.7 years.
However, Dr. Sosman noted that patients in this trial have experienced several toxic side effects, such as hypophysitis and colitis, alongside immune-related adverse events. In this trial, 52% of ipilimumab-treated patients discontinued treatment and 1.1% died as a result of treatment toxicity. Also, the ipilimumab dosage used is not approved in the United States, and would significantly increase the monetary costs in a therapeutic setting. Nevertheless, the study seems to provide enough evidence for the use of immune checkpoint inhibitors as an adjuvant in late-stage melanoma.
Dr. Sosman concludes the debate by encouraging the medical and scientific community to re-think and design future clinical trials aimed at targeting new checkpoint inhibitors.
You can watch the panel in its entirety here:
