Immunotherapy before liver cancer surgery can kill tumor and possibly residual cancer cells

Immunotherapy given before surgery caused death from cancerous liver tumors in a third of patients enrolled in a first-of-its-kind clinical trial, Mount Sinai researchers report in The Lancet Gastroenterology and Hepatology in January.

The results of the phase 2 trial suggest that neoadjuvant immunotherapy – therapy given before surgery – can kill not only the tumor, but also the microscopic cancer cells that surgery would miss and which could later cause recurrence or metastasis. cancer, the researchers said. Indeed, the therapy teaches the immune system to fight any recurrence.

“Ultimately, we think it’s better for the patient to receive immunotherapy before surgery, because people are healthier before metastasis and their immune systems are in better shape to fight cancer,” he said. lead author Thomas Marron, MD, PhD, director of the Early Phase Trials Unit at the Tisch Cancer Institute and associate professor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai. “This study, along with trials of neoadjuvant immunotherapy in many other tumor types, supports the need for ongoing evaluation of perioperative immunotherapy to reduce recurrence rates.”

Dr Marron added: “Usually when the cancer comes back it is no longer a curable disease. Larger trials in the future will help define the usefulness, safety and survival of the neoadjuvant immunotherapy, particularly this type of PD-1 blockade.”

Liver cancer, the most common type of which is known as hepatocellular carcinoma (HCC), is the third leading cause of cancer-related death worldwide. While immunotherapies have changed the prognosis of patients with advanced HCC, the majority of patients still die from this disease. Although liver cancer surgery often appears to be successful, in more than half of patients the cancer recurs, either due to residual micrometastatic disease or in some cases to an entirely new tumor, highlighting the potential benefit of neoadjuvant therapy to improve survival.

The results of this study are important because to date, no treatment administered before or shortly after surgery has demonstrated a real improvement in the survival of patients with liver cancer.

Researchers gave 21 patients with early-stage liver cancer two cycles of the immunotherapy agent cemiplimab, an anti-PD-1 antibody, before their surgery in late 2020. Doctors studied the death tumor and anti-cancer immune system activation via magnetic resonance imaging and blood, tumor and stool samples.

They found that in a third of patients, a large portion of their tumors died before surgery. Patients whose immune systems were already working against the cancer tended to have a greater response to immunotherapy, suggesting that the immune system was more activated and would kill any microscopic residue of cancer. Tumor death in response to neoadjuvant therapy is an indication of improved outcomes in many types of cancer, and researchers are currently following patients to assess whether this is also true for HCC.

This study was able to measure the response of the immune system in a new way. Dr. Marron and his colleagues used a new collaborative approach between researchers and clinicians: the Neoadjuvant Research Group to Evaluate Therapeutics or TARGET, which maximizes the useful information that can be gleaned from smaller neoadjuvant clinical trials. The TARGET platform focuses on coordinating detailed, real-time profiling of the immune system response in patients receiving cancer immunotherapy as neoadjuvant therapy.

The TARGET platform showed how blocking PD1 increased the number of activated immune cells that invaded HCC tumors, induced tumor necrosis and shrank tumors before surgery. The platform helped researchers determine that blocking PD1 is likely beneficial in HCC, but since only some patients had a robust response, immunotherapy may need to be used in combination with other treatments. The purpose of in-depth analysis of tissue samples is to identify biomarkers – biological identifiers – that will help show who will respond well and who will not respond well to therapy. TARGET’s goal is to identify the optimal therapy for each patient and reduce the likelihood that suboptimal treatments will enter large-scale Phase 3 trials, which wastes resources, time and money. patient efforts.

“Normally you don’t study in such detail how drugs work in humans,” Dr. Marron said. “When you perform single biopsies, you get very little tissue, and the scan often does not yield detailed information about the cancer or immune system response. With this platform’s scan, you get multiple biopsies before the treatment as well as blood and stool samples. Then when the tumor is removed in surgery, we analyze that and more blood and stool samples, so we have a lot of detailed information about what’s going on at the microscope than ever before. detail.”

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