Desmoplastic melanoma, an usually deeply invasive illness occurring in older adults, confirmed a uniquely favorable response to neoadjuvant pembrolizumab (Keytruda) in a small examine, with most sufferers happening to keep away from postoperative radiation remedy.
In what’s considered the primary examine of neoadjuvant use of an anti-PD1 immunotherapy in desmoplastic melanoma, the postexcision full response charges have been almost twice the charges reported with the therapy in different superior melanomas, the investigators famous.
“No residual viable tumor was discovered on the main website in an astounding 81% of those sufferers,” stated Vernon Okay. Sondak, MD, chair of the Division of Cutaneous Oncology on the Moffitt Most cancers Heart, in Tampa, Florida.
Solely considered one of 21 sufferers required radiation after their surgical procedure. “We’d have in any other case anticipated nearly all of those sufferers to be radiated in most facilities,” Sondak stated.
The brand new outcomes have been offered on the Worldwide Convention on Surgical Most cancers Care (SSO 2023).
Approached for touch upon the examine, Mary Sue Brady, MD, a surgical oncologist at Memorial Sloan Kettering Most cancers Heart in New York, agreed that the response charges have been spectacular.
“I’m unaware of another remedy that produces such a excessive response price within the neoadjuvant setting on this group of sufferers,” she stated, noting that almost all of sufferers (23) on this small examine had main or recurrent illness.
“Included on this report have been sufferers with each ‘blended’ and ‘pure’ desmoplastic subtypes, so that is notably encouraging,” she added. “This melanoma subtype will be notably tough to deal with with upfront surgical procedure because the tumors are sometimes fairly deep or domestically superior.”
Desmoplastic melanoma, which usually happens on the top or neck of older sufferers, usually requires radical resection, leading to a big defect that not solely might require advanced reconstruction but additionally carries a excessive danger for native recurrence and the necessity for postoperative radiation, she defined.
First Examine of Neoadjuvant Remedy in Desmoplastic Melanoma
Sondak reported a publish hoc evaluation that included 28 sufferers with stage IIB, IIC, or III desmoplastic melanoma who have been enrolled within the SWOG S1512 potential trial.
Many of the tumors (n = 23; 79%) have been main, and 5 tumors have been recurrent or had nodal metastases.
These sufferers had a median age of 75 years, and all sufferers had tumor current firstly of therapy.
They have been handled with as much as 4 doses of intravenous pembrolizumab 200 mg each 3 weeks earlier than a deliberate surgical procedure.
Not one of the sufferers have been prevented from receiving surgical procedure owing to illness development or metastasis. Of the 26 sufferers who obtained vast excision of their main or recurrent illness, 21 (81%) had no residual, viable tumor on the website on closing pathology.
Re-excision was crucial in solely two sufferers, together with one who underwent re-excision twice, to attain destructive margins, and one affected person obtained postoperative radiation.
In 17 sufferers with clinically node-negative illness, sentinel node biopsy was carried out, with one (6%) affected person discovered to have a optimistic node. Three different sufferers with scientific stage III illness obtained a lymphadenectomy; of those, just one (33%) had a residual viable tumor.
Total, a pathologic full response, with no remaining viable tumor at any surgical website, was seen in 55% of sufferers.
With a median follow-up of 24 months, two native recurrences have been reported, every occurring in sufferers who didn’t have a pathologic full response.
One of many sufferers with a recurrence died of melanoma, and one other three sufferers died of different causes that weren’t associated to melanoma or its therapy. Sondak famous that given the older inhabitants of sufferers with desmoplastic melanoma, such mortalities will not be uncommon.
The outcomes recommend that this kind of melanoma has an exceptionally excessive sensitivity to neoadjuvant therapy.
Compared, in a latest major study carried out by the SWOG Most cancers Analysis Community in sufferers with stage III melanoma utilizing three preoperative doses of pembrolizumab, the pathologic full response price was within the 20%-30% vary.
“The truth that our pathologic full response was a lot increased [55%] — total twice what we’d anticipate — is consistent with our expectation going into the examine that desmoplastic melanomas could be extra delicate to neoadjuvant pembrolizumab,” Sondak instructed Medscape Medical Information.
As well as, the pace of the response was notable, Sondak stated.
“In most neoadjuvant melanoma sufferers with optimistic nodes, the node remains to be enlarged even when it is a pathologic full response, however after a number of cycles of neoadjuvant pembrolizumab therapy, tumors disappeared and lots of sufferers have been fully again to regular in a brief time period,” he stated.
Relating to the truth that just one affected person required postoperative radiation, Sondak famous that “at our establishment, the place now we have a substantial amount of expertise with treating desmoplastic melanoma with commonplace surgical approaches, nearly 100% of those sufferers would have obtained postoperative radiation, and we’d have anticipated a better price of optimistic margins and certain a better price of optimistic sentinel nodes as nicely.”
Time will inform how or if the favorable responses translate to improved survival.
“The typical follow-up was about 2 years, and up to now, the outcomes are holding regular,” Sondak stated. Nevertheless, “we do not but know if these sufferers could have a greater survival price than if we had merely waited for his or her most cancers to reoccur after which used the very same drug therapy,” he acknowledged.
“For now, now we have to acknowledge that we merely do not know the way a lot our sufferers benefited from neoadjuvant remedy in comparison with an ordinary surgical procedure adopted by postoperative radiation, with or with out immunotherapy strategy, and future analysis might want to look at that,” he continued.
Nevertheless, the mechanisms of immunotherapy bode nicely for encouraging outcomes.
“Certainly, one of many actual benefits of immunotherapy is that should you can stimulate the physique’s immune system to reject a tumor, the immune cells stay on guard in opposition to recurrence for a few years thereafter,” Sondak stated. “This sturdy exercise is a key cause why neoadjuvant remedy is being pursued so enthusiastically throughout totally different melanoma sorts and levels,” he added.
“Having stated that, it is possible that a minimum of some sufferers will but develop recurrence, maybe if their immune system is weakened in some trend or if the tumor merely learns to evade these immune cells.”
With the quickly increasing ageing inhabitants, and desmoplastic melanoma occurring predominantly in older individuals, clinicians can possible anticipate to see a rise within the charges of this kind of illness, Sondak commented.
“The incidence of melanoma within the US is rising sooner than nearly another most cancers kind, and between that and our ageing inhabitants, it is a digital certainty we’ll see extra desmoplastic melanomas sooner or later,” he stated.
The examine was funded partly by Merck Sharp & Dohme LLC. Sondak is a compensated guide for Alkermes, Bristol-Myers Squibb, Eisai, Genesis Drug Discovery & Growth, Iovance, Merck, Novartis, Regeneron, and Ultimovacs and receives analysis funding from Neogene Therapeutics, Skyline, and Turnstone. Brady had no disclosures to report.
Worldwide Convention on Surgical Most cancers Care (SSO 2023). Summary 57. Offered March 24, 2023.