Adding immunotherapy before melanoma surgery significantly improves survival in these patients. This has been seen in a randomized phase 2 clinical trial carried out in patients with stage III-IV melanoma and published in “The New England Journal of Medicine” which represents a breakthrough in the treatment of this skin cancer and could change the way high-risk melanoma is routinely treated.
“This is the first clinical trial that shows that neoadjuvant therapy -the one administered before surgery- is superior to the same therapy administered in the adjuvant setting -after surgery”, stated the Spanish researcher. Anthony Ribas, director of the Tumor Immunology Program at the UCLA Jonsson Comprehensive Cancer Center. “This is because it is better to activate the immune system within the cancer before removing it with surgery.”
Researchers at the UCLA Jonsson Comprehensive Cancer Center designed the study and treatment regimen based on how pembrolizumab, used in this study, and other similar drugs, called immune checkpoint inhibitors, are thought to work. Pembrolizumab is a PD-1 inhibitor that lock a checkpoint immune system that reduces the immune system’s response to cancer.
The therapy unleashes the anti-tumor immune response—sometimes called “unwinding the brakes on the immune system”—allowing immune cells already at the tumor site to proliferate and attack cancer cells at that site or elsewhere in the tumor. body.
“Based on these insights, it is likely that removal of most of the tumor, along with tumor-infiltrating immune cells contained in the surgical sample, will eliminate some or even most of the potential antitumor immune cells that would proliferate after blockade.” of PD-1”, explains Ribas.
“Our theory has been – and this study confirms it – that starting anti-PD-1 blocking therapy before surgery could activate more antitumor immune cells and improve clinical outcomes compared to the same amount of drug given after surgery.” surgery”.
The therapy unleashes the antitumor immune response by allowing already existing immune cells to proliferate and attack cancer cells.
“It’s not just what you give, but when you give it,” says first author Sapna Patel. The investigators found that, at two years, 72% of patients in the group receiving neoadjuvant pembrolizumab followed by adjuvant pembrolizumab were event-free (unsuccessful surgery, melanoma recurrence, or death), compared with 49% of patients in the group that only received adjuvant pembrolizumab.
“The study highlights that the timing of an immune checkpoint inhibitor in relation to surgery can have a large effect on patient outcomes, despite the fact that the same systemic treatment was given to both groups. of study,” he adds Bartosz Chmielowski, study co-author. “Our results demonstrate a significant benefit when immunotherapy is started before surgery to generate an immune response while the bulk of the cancer and antitumor immune cells remain intact.”