Immunotherapy before surgery for advanced melanoma reduces risk of recurrence

Melanoma is the most aggressive and lethal type of skin cancer, especially due to the high probability of spreading to other organs. The standard treatment of the disease for patients with metastasis in regional lymph nodes (stage 3) is based on removal of the tumor associated with the application of immunotherapy for one year to reduce the risk of recurrence.

Now, a study presented during Asco 2024the annual meeting of the American Society of Clinical Oncology, held in Chicago, United States, is expected to change clinical practice.

Researchers from several institutions in Australia and the Netherlands have demonstrated that the use of just two cycles of a combined immunotherapy, before surgery, increases the patients’ chance of cure and reduces the risk of tumor reappearance.

To reach the results, the researchers carried out a randomized study with 423 patients, divided into two groups: the control group received conventional treatment (surgery first + nivolumab for 12 months) and the other half received neoadjuvant treatment, with two cycles of immunotherapy. combination (nivolumab and ipilimumab for six weeks) and then surgery.

The results showed that 60% of patients in the group that received the neoadjuvant strategy (two cycles of preoperative immunotherapy) had a complete pathological response or greater, that is, more than 90% of the tumor was eliminated – which is considered practically a healing by experts. The other 40%, who did not achieve this response, were able to continue immunotherapy in the postoperative period to complement it.

Furthermore, the study demonstrated that the risk of recurrence is 70% lower among those who received preoperative immunotherapy, compared to those who received standard treatment. “Most patients had this fantastic response with much shorter treatment. The strategy practically evaporated the entire disease and there were almost no cases of recurrence. The other 40% will continue with complementary treatment because it was possible to identify a population at higher risk for recurrence and that in fact needs longer treatment”, analyzes Gustavo Schvartsman, clinical oncologist at Hospital Israelita Albert Einstein, who attended the presentation of the new study during Asco.

The side effects were similar in both scenarios, although patients who received the combination of the two drugs felt slightly more intense effects than those who were in the single drug scenario. “But the shorter duration of the treatment meant that the side effect was also shorter”, highlights Schvartsman.

The benefits of immunotherapy

Melanoma represents around 4% of skin tumors. In Brazil, the National Cancer Institute (Inca) estimates the occurrence of 9 thousand cases per year and almost 2 thousand deaths due to the problem. The disease is subdivided into four stages, depending on severity. Patients with melanoma in stages 1 and 2 have a localized tumor, without metastases. People in stage 3 have nearby metastases, usually in lymph nodes – and they are the ones who undergo surgery and immunotherapy. Patients in stage 4 are those with the most advanced melanoma, with distant metastases and spread to other organs.

For some years now, science has known that melanoma is an extremely immunogenic type of cancer, that is, it responds well to treatment with immunotherapy – which is nothing more than a way of teaching the body to recognize cancer cells and fight against them. they. Therefore, there are several ongoing studies that test different ways of applying immunotherapy to treat the disease.

According to Schvartsman, the study presented at Asco was designed based on several previous ones, which evaluated the strategy of using preoperative immunotherapy as something potentially better for the patient. This is because, according to the doctor, the results were already demonstrating that the immune system usually works better when immunotherapy is administered before removing the tumor.

“In this scenario (of immunotherapy applied before tumor removal) you have a patient with a healthier immune system, as he has not yet undergone surgery. Furthermore, the tumor is still present as a source of recognition by the immune system. When we remove the tumor, we remove what the immune system needs to look for. And the surgery also severs the blood vessels, cutting off access to the tumor. If you cut the vascularization, the immune system cannot reach the cancer and recognize it”, explains the oncologist.

Immunotherapy in SUS

The two immunotherapeutics used in the study are already approved in Brazil, but, for now, they are widely available only in the private network. Although there is a recommendation from the National Commission for the Incorporation of Technologies (Conitec) in the Unified Health System (SUS) for the incorporation of drugs into the public network, they are still not part of the list of medications used routinely for melanoma patients treated by the SUS.

This is because they are high-cost drugs and the adherence of specialized centers comes up against the price. “The strategy of bringing forward immunotherapy greatly shortens the treatment and considerably reduces the associated cost. Despite there being two medicines, the number of doses to be used is so much smaller that the final cost of the treatment is cheaper”, observes the oncologist.

For Luciana Holtz, president of the Oncoguia Institute, the results of this study may favor the process of incorporating these immunotherapeutics into the public network, precisely because fewer doses are needed. “Although we already have immunotherapy incorporated into the SUS by Conitec, it is still not available equitably to everyone who can benefit. The centers that are able to buy do so, but not all of them. So not all patients have access. I believe that this new study can indeed help us seek these changes and benefit SUS patients”, says Holtz.

For the Einstein oncologist, there is no doubt that clinical practice for supplementary health patients must change with these results. “The conclusion of the work is unequivocal. From now on, all patients with metastatic melanoma must undergo a cycle of immunotherapy preoperatively. In addition to being cheaper, because it involves fewer doses of medication, the strategy significantly increases the chances of a cure. There is no better scenario”, he adds.