Carol Rossier Bradford, MD
Advancements in biopsy techniques, as well as several recently approved new therapeutic agents, have made a significant difference in outcomes for patients with melanoma of the head and neck, says Carol Rossier Bradford, MD, a head and neck surgeon and professor of Otolaryngology at the University of Michigan Health System.
In a 10-year follow-up of the Multicenter Selective Lymphadenectomy Trial (MSLT-1), the use of sentinel-node biopsies to identify patients with clinically occult nodal metastases was shown to significantly increase disease-free survival (DFS) rates compared with nodal observation in patients with primary cutaneous melanomas.
Sentinel-node biopsies offer an alternative to elective complete lymphadenectomy, which can have potential complications.
During the phase III MSLT-1 trial, 1661 patients with primary cutaneous melanomas underwent randomization and 1638 were included in the 10-year follow-up. Of the initial patient population, 1347 had intermediate-thickness (1.20-3.50 mm) primary melanomas and 314 had thick primary melanomas (>3.50 mm).
Forty percent of patients were randomized to undergo wide excision and nodal observation with lymphadenectomy for nodal relapse; 60% were randomized to undergo wide excision and sentinel-node biopsy with intermediate lymphadenectomy for nodal metastases detected on biopsy.
DFS rate was the primary endpoint of the study. Among patients with intermediate-thickness melanomas the DFS rate was 71.3±1.8% in the sentinel-node biopsy group versus 64.7±2.3% in the observation group.
Among those with thick primary melanomas, the DFS rate was 50.7±4.0% in the sentinel-node biopsy group versus 40.5±4.7% in the observation group.
In addition, FDA approvals for novel agents have rapidly expanded in melanoma, including the immunotherapy agents ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), talimogene laherparepvec (T-VEC; Imlygic) and the targeted agents cobimetinib (Cotellic), dabrafenib (Tafinlar), and trametinib (Mekinist), which were all approved in the past few years. These agents have greatly influenced the treatment of head and neck melanoma, says Bradford.
“In the past 5 to 7 years, there have been numerous new drugs FDA approved for melanoma; it is truly amazing,” says Bradford. “The speed of discovery has been quite rapid.”
In an interview with OncLive
, Bradford discusses the treatment and surgical outlook for head and neck melanoma, as well as other subtypes of the disease. She also discusses the growing need for more awareness of melanoma risk and prevention.
OncLive: What did we learn from MSLT-1 about the role of sentinel-node biopsy in head and neck melanoma?
: MSLT-1 looked at patients with stage I/II melanoma that was confined to the skin and not yet metastatic. Patients were randomized to either receive wide local excision alone or wide local excision with sentinel-node biopsy.
Recently, 10-year follow-up results were published. Those results indicate that patients whose regional lymph nodes are diagnosed by a sentinel-node biopsy have improved survival relative to those who are in the “watch and wait” or observation group.
Based on this trial, most patients with cutaneous melanoma of the head and neck, or anywhere on the body, are offered sentinel-node biopsy as a staging procedure to select those patients who will benefit from early therapeutic lymph node dissection.
Sentinel-node biopsy really came into play in the late 1990s and is now utilized more by surgeons to detect early stage III disease. We now know that only that subset needs therapeutic lymph node dissection, not everyone. There is really no role for elective nodal dissection anymore.
What new systemic therapies for melanoma of the head and neck are you excited about?
I am not a medical oncologist but, as a head and neck surgeon, I do have a number of patients who developed systemic relapse and then significantly benefited from some of the most recently approved novel therapies.
Immunotherapies are making a big impact, including ipilimumab. PD-1 inhibitors are also very exciting, and they are having remarkable success combating melanoma. Because melanomas are very immunogenic, immunotherapy is a very effective strategy. We are starting to think about curing stage IV disease with this agent, which is very exciting.
For patients whose melanomas harbor BRAF mutations, there are a couple of targeted therapies being marketed in that space, which are exciting. They can also be used in combination with MEK inhibitors and that is proving to improve survival. There is an array of very effective systemic drugs; clinical trials are ongoing to determine which 1, 2, or 3 treatments are going to work together the best.
I think the greatest impact recently, for melanoma of the head and neck, is these novel systemic therapies.
What are the biggest unanswered questions that remain in head and neck melanoma?
The challenge with head and neck melanoma—and melanoma in general—is that it is striking patients younger and younger. Tanning booths and sun exposure are still a huge problem. Disappointedly, melanoma is one of the few cancers in the United States where incidence is still increasing. What is so bad about it is that it really strikes people in the prime of their life and many lives are lost to it. A deadly disease is not worth trying to look beautiful.
Looking ahead, what do you see for the future treatment paradigm in head and neck melanoma?
Melanoma will still be a primarily surgical disease and will be treated as such along with early detection, public awareness, wide local excision, and, for patients whose melanomas are greater than 1 millimeter by the Breslow’s depth, use sentinel-node biopsy as a staging tool. I don’t envision that changing a lot.
The biggest advances will be in figuring out how to eradicate advanced stage recurrent/refractory melanoma with these novel targeted agents and immunotherapy agents.
Morton DL, Thompson JF, Cochran AJ, et al. Final report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609.