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Neoadjuvant immunotherapy improves outlook in high-risk melanoma

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Patients with high-risk melanoma who received the immunotherapy drug pembrolizumab both before and after surgery to eliminate cancerous tissue had a significantly lower threat of their cancer recurring than similar patients who received the drug only after surgery.

These results from the study by the SWOG Cancer Research Network, a cancer group funded by the National Cancer Institute (NCI), will undoubtedly be presented at a Presidential Symposium at the European Society of Medical Oncology (ESMO) Congress 2022 in Paris on Sept. 11, 2022 (Abstract LBA6).

The analysis, referred to as S1801, was led by Sapna Patel, MD, chair of the SWOG committee and associate professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center.

“It isn’t precisely what you give, it’s once you give it. The S1801 study demonstrates exactly the same treatment for resectable melanoma given before can generate better outcomes,” Patel said. “In cases like this, we used the immune checkpoint inhibitor pembrolizumab. This treatment depends on the current presence of pre-existing T cells pressing cancer cells in your body to create an immune response, and we discovered that starting treatment prior to the melanoma is removedand with it the majority of tumor-specific T cellsleads to a larger response than giving it after surgery.”

The mechanism of action of immune checkpoint inhibitors such as for example pembrolizumab is frequently referred to as “taking the brakes off” the immune system’s reaction to tumor cells. The S1801 researchers hypothesized that there will be a larger anti-tumor immune response and longer immunologic memory if pembrolizumab was administered as the melanoma tumor was still in your body instead of from then on tumor have been removed, once the will be responding primarily to micrometastatic .

To check this hypothesis, S1801 investigators enrolled 345 participants with stage IIIB through stage IV melanoma that has been deemed operable. Participants ages 18-90 were randomized to get either upfront surgery accompanied by 200 mg of pembrolizumab every three weeks (referred to as adjuvant therapy) for a complete of 18 doses, or even to 200 mg of pembrolizumab every three weeks for three doses before surgery (referred to as neoadjuvant therapy), then yet another 15 doses following surgery.

The principal endpoint measured was the duration of event-free survival, thought as enough time from randomization to the occurrence of 1 of the next: or toxicity that led to not receiving surgery, failure to begin with adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

With a median follow-up of 14.7 months, event-free survival was significantly longer in the neoadjuvant therapy arm, with a hazard ratio of 0.58 in comparison with the adjuvant therapy arm, which corresponds to a 42% lower event rate in the patients receiving the neoadjuvant regimen.

“Our study noted a substantial improvement in event-free survival in the neoadjuvant regimen when compared to adjuvant regimen,” Patel said. “Importantly, an identical amount of patients in both arms experienced events before initiating adjuvant pembrolizumab, however the rate of events after initiating adjuvant therapy was higher (worse) in the adjuvant arm.”

The researchers discovered that the power from neoadjuvant was consistent across a variety of factors including patient age, sex, performance status, and stage of disease. In addition they discovered that the rates of adverse events (unwanted effects) were similar across both arms of the analysis and that neoadjuvant pembrolizumab didn’t result in a rise in adverse events linked to surgery.

“In line with the findings from S1801, patients with high-risk melanoma should start immunotherapy ahead of surgery to create an as the almost all the melanoma and the anti-tumor T cells are intact,” Patel said. “Future studies can explore de-escalation approaches for both surgery and , along with approaches for patients whose melanoma will not react to .”



More info: Patel S et al., “LBA6Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801),” Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089 https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjvuant-versus-adjuvant-pembrolizumab-for-resected-stage-iii-iv-melanoma-swog-s1801

Provided bySWOG Cancer Research Network

Citation: Neoadjuvant immunotherapy improves outlook in high-risk melanoma (2022, September 11) retrieved 12 September 2022 from https://medicalxpress.com/news/2022-09-neoadjuvant-immunotherapy-outlook-high-risk-melanoma.html

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