Jeffrey Weber, MD, PhD
Melanoma has a high cure rate when diagnosed and treated at an early stage, but patients with high-risk melanomas, including stage III disease, remain at increased risk of recurrence and mortality even after definitive surgical treatment. Adjuvant therapy has the potential to improve long-term outcomes in these patients but remains underutilized. In a study presented at the 2018 American Society of Clinical Oncology Annual Meeting, less than 29% of patients with stage III melanoma received adjuvant therapy.1
This may not be surprising: until recently, the only FDA-approved adjuvant treatment option in this setting was interferon (IFN)-α, a drug with variable efficacy and treatment-limiting toxicities.2
The advent of checkpoint inhibitors and targeted agents have given oncologists more to work with.
“There has been a lot of action and research and development in the adjuvant field in melanoma within the last year, with 3 very impressive trials and multiple new approvals,” moderator Jeffrey S. Weber, MD, PhD, said during a recent OncLive Peer Exchange®
on the evolving armamentarium in advanced melanoma.
More patients than ever before may now be good candidates for adjuvant therapy and derive long-term benefits from it, but new data and expanding treatment options have led to many new questions on how to optimize treatment. During the Peer Exchange, a group of melanoma experts shared their insights on who should undergo completion lymph node dissection, which molecular testing and adjuvant treatments to consider, what staging challenges need to be overcome, and when to implement and stop adjuvant therapy.
Stage III Melanoma: Who's Resectable?
Stage III melanoma is now known to be a heterogenous entity, and the panel noted that not all patients with this disease should receive a completion lymph-node dissection, unlike previously thought. “In the stage III setting, we really have to divide patients into the ones who have microscopic disease in their lymph nodes versus the patients who present with bulky disease and macroscopic disease,” Robert Andtbacka, MD, CM, said, noting that 2 recent studies have shown that patients with microscopic disease can do just as well with ultrasound follow-up.3,4
In the MSLT-II, the larger of the 2 trials discussed and one in which Andtbacka is an investigator, completion lymph-node dissection did not lead to improvement in melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis.3 At a median follow-up of 43 months, the mean 3-year rate of melanoma-specific survival in the per-protocol analysis was almost identical between the dissection and observation groups, at 86% ± 1.3% and 86% ± 1.2%, respectively, though the rate of disease-free survival was somewhat higher at 68 ± 1.7% versus 63 ± 1.7%, respectively.3 In the multicenter, randomized DeCOG-SLT trial, no benefit was observed with dissection versus observation for distant metastasis- free survival, recurrence-free survival, or overall survival after a median follow-up of 72 months among 473 patients with a positive sentinel node.4
“One of the caveats with both of these studies was that the amount of tumor in the sentinel lymph node was fairly small. When we think about these patients, we have to remember that most patients had only 1 positive sentinel lymph node,” Andtbacka said. He explained that in his practice, he has found the ultrasound approach to be viable for patients with a low disease burden in their sentinel lymph nodes and that more than half of these patients prefer ultrasound over receiving surgery. In general, he said, he reserves complete lymph-node resection for patients with more extensive disease in their lymph node basin or with melanoma in multiple lymph nodes and that these are the patients with whom he also discusses adjuvant therapy, because of their high risk of local and distant recurrence.
BRAF, PD-L1, or Both: What to Test?
Approximately 50% of advanced melanomas are known to harbor BRAF
and in patients with BRAF
V600–mutated melanoma, targeted therapy with BRAF
inhibitors is associated with significant long-term benefit. The panel agreed that obtaining BRAF
mutation status early is important. “We now try to do [BRAF testing] on the majority of patients, because of the decisions to be made in the adjuvant setting,” Omid Hamid, MD, said.