{"id":28393,"date":"2022-10-12T12:00:00","date_gmt":"2022-10-12T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2022\/melanoma-immunotherapy-before-surgery"},"modified":"2024-11-03T15:13:14","modified_gmt":"2024-11-03T15:13:14","slug":"immunotherapy-before-surgery-appears-effective-for-some-with-melanoma","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/immunotherapy-before-surgery-appears-effective-for-some-with-melanoma\/","title":{"rendered":"Immunotherapy before Surgery Appears Effective for Some with Melanoma"},"content":{"rendered":"

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Giving patients immunotherapy before surgery causes the immune system to attack the tumor and cancer cells elsewhere in the body, even after surgery.<\/p>\n

Credit: Used with permission from Sapna Patel<\/p>\n<\/p><\/div>\n<\/figcaption><\/figure>\n<\/p><\/div>\n

The treatment of melanoma has been transformed over the past decade, perhaps more than for any other cancer. And, based on the initial results from an NCI-funded clinical trial<\/a>, another treatment enhancement for this often aggressive<\/a> type of skin cancer is on the horizon. The approach appears to benefit people with advanced forms of the disease but whose cancer can still be treated with surgery.<\/p>\n

One group of people in the trial had surgery to remove their tumors and then received periodic doses of the immunotherapy drug pembrolizumab (Keytruda)<\/a> over the next year, called adjuvant therapy<\/a>. The other group received several doses of pembrolizumab before surgery, called neoadjuvant therapy<\/a>, followed by adjuvant therapy with pembrolizumab over the 10 months after surgery.<\/p>\n

Those few doses of pembrolizumab before surgery look to have paid off: there was a substantially lower risk of the cancer coming back among patients who received neoadjuvant treatment<\/a> compared with those who only received adjuvant treatment.<\/p>\n

And in about 20% of patients treated with pembrolizumab before surgery, their original tumor(s) disappeared entirely.<\/p>\n

The results were presented September 11 at the European Society for Medical Oncology (ESMO) meeting in Paris.<\/p>\n

The trial, which was conducted by the SWOG Cancer Research Network, hasn\u2019t gone on long enough to determine whether neoadjuvant therapy with pembrolizumab improves how long patients live overall. But the results so far are very encouraging, said the trial\u2019s lead investigator, Sapna Patel, M.D., of the University of Texas MD Anderson Cancer Center.<\/p>\n

Based on the findings, Dr. Patel said she believes treatment guidelines from professional oncology organizations may be revised to recommend neoadjuvant pembrolizumab for people with this form of melanoma. <\/p>\n

\u201cSurgery still has a role\u201d for these patients, she continued, but the timing of surgery may well change.<\/p>\n

Other experts on treating melanoma agreed. During a session on the trial\u2019s results at the ESMO meeting, Teresa Petrella, M.D., of the Sunnybrook Odette Cancer Centre in Toronto, said the study \u201csupports the idea\u201d that neoadjuvant therapy and adjuvant therapy is more effective than adjuvant therapy alone.<\/p>\n

Leaving the tumor intact to kickstart the immune response<\/h2>\n

Adjuvant therapy has become a mainstay for treatment of many cancers, including melanoma. The premise behind adjuvant therapy is to kill any cancer cells not removed via surgery and those that are lurking elsewhere in the body but can\u2019t be detected by any available methods. These cancer cells are often called micro-metastases.<\/p>\n

For the trial presented at the ESMO meeting, called S1801, participants could have cancer that had spread to tissue near the original tumor (such as nearby lymph nodes<\/a>) or even traveled to distant parts of the body. However, surgery was still considered to be an effective way to help treat their cancer.<\/p>\n

For people who can still be treated with surgery, adjuvant therapy\u2014either with immune-based treatments or a targeted therapy<\/a> if their tumors have a specific genetic mutation<\/a>\u2014is now a standard practice.<\/p>\n

In the S1801 trial, the researchers wanted to test whether starting immunotherapy before surgery could exploit the immune cells<\/a> that are already present in and around patients\u2019 tumors. <\/p>\n

The immune cells are there because \u201cthe immune system has already recognized the tumor\u201d as dangerous, explained Elad Sharon, M.D., of NCI\u2019s Cancer Therapy Evaluation Program<\/a>, who helped designed the study. The immune response just hasn\u2019t been strong enough to destroy the tumor.<\/p>\n

Immunotherapy is intended to give this existing immune response a massive jolt, spawning a more lethal attack. \u201cBut when you [only] give it after surgery, when there’s no disease there, there’s the legitimate risk that there isn’t much left for the immune system to respond to,\u201d he said.<\/p>\n

With the tumor in place when those first doses of pembrolizumab are given, the drug can dramatically increase the number of T cells<\/a> capable of recognizing and attacking the tumor, Dr. Patel said. \u201cAnd after we remove that tumor, those T cells then migrate into the circulation, and now we have a higher number in circulation to go after [micro-metastases].\u201d<\/p>\n

Neoadjuvant pembrolizumab improves event-free survival<\/h2>\n

A total of 313 patients were enrolled in the phase 2 trial. All had stage 3 or 4 melanoma.<\/p>\n

Participants were randomly selected to have surgery followed by 18 doses of pembrolizumab (given intravenously<\/a>) over the next year or to receive the first three doses of pembrolizumab during the 2 months before surgery and the remaining 15 doses over the 10 months following surgery.<\/p>\n

The study\u2019s primary measure was whether receiving the three pembrolizumab doses before surgery would improve how long people lived without experiencing specific events, known as event-free survival. <\/p>\n

At 2 years, 72% of those in the neoadjuvant therapy group were still alive without an event, compared with 49% in the adjuvant therapy group, Dr. Patel reported at the ESMO meeting.<\/p>\n