Adding immune checkpoint inhibitors to neoadjuvant and adjuvant therapy can increase the occurrence of treatment-related side effects, leading to treatment discontinuation, according to findings that were published in The Lancet.
Although incorporating immunotherapy into prior- and post-surgical therapies has shown outcome improvements, treatment-related side effects need further investigation, according to the researcher.
“The goal of our study was to evaluate how adding immune checkpoint blockade to conventional perioperative (neoadjuvant and adjuvant) therapy affects the incidence of severe (grade 3-4) and fatal treatment-related adverse events,” noted Dr. Yu Fujiwara, Hematology/Oncology, Department of Medicine at the Roswell Park Comprehensive Cancer Center and Dr. Abdul Rafeh Naqash, Assistant Professor of Medicine, Medical Oncology/ TSET Phase 1 Program at the Stephenson Cancer Center at The University of Oklahoma, in a recent interview with CURE®.
Immune checkpoint inhibitors were studied based on their effect with perioperative therapy within the patient population.
“Immune checkpoint blockade is a cancer treatment referred to as ‘immunotherapy’ in general. Immune checkpoint blockade inhibits “inhibitory immune checkpoints” that are mainly expressed on the surface of effector T-cells. By blocking these checkpoints, our T-cells can recognize tumor cells again, and start attacking cancer cells by using our own immune system. It is relatively tolerable more than classic chemotherapy but is known to cause unique adverse reactions called immune-related side events,” said Fujiwara and Naqash.
The study identified 28 randomized-controlled trials, consisting of 16,976 patients that added immunotherapy as treatment before and after surgery.
“We used a method called meta-analysis to pool odds ratios (ORs) of treatment-related deaths, any grade and grade 3–4 treatment-related adverse events, serious adverse events, and adverse events leading to treatment discontinuation. We found that the addition of immune checkpoint blockade was not significantly associated with increased treatment-related deaths,” Fujiwara and Naqash noted.
Within 9,864 patients treated with immunotherapy, there were 40 fatal toxicities, the most common being pneumonitis, followed by myocarditis and colitis. Adding immunotherapy to treatment increased grade 3-4 treatment- related side effects, with the possibility of treatment discontinuation.
“The immune checkpoint blockade versus placebo design primarily used as adjuvant therapy was associated with increased incidence of treatment-related deaths and grade 3–4 adverse events, whereas the addition of immune checkpoint blockade in the neoadjuvant setting was not associated with increased incidence of treatment-related death or grade 3–4 adverse events,” Fujiwara and Naqash stated.
The addition of immune checkpoint inhibitors to treatment before and after surgery resulted in more moderate to severe treatment-related side effects, leading to treatment discontinuation within the patient population.
“Our study is not against the use of perioperative immune checkpoint blockade but rather to facilitate discussion between health care providers and patients before and during the perioperative therapy utilizing immune checkpoint blockade. Our study would be helpful to provide accurate information about the risk of severe adverse events from immune checkpoint blockade-containing perioperative regimen,” according to Fujiwara and Naqash.
This information is beneficial for upcoming clinical trials exploring the use of additional immunotherapy within cancer treatments.
“We expect that more patients will receive immune checkpoint blockade either before or after the surgical procedure in 2024. We hope that our study would be helpful to provide safety information of this strategy for patients and give safety insights in designing clinical trials utilizing immune checkpoint blockade in the earlier-stage settings for patients with cancer,” said Fujiwara and Naqash.
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