Nivolumab showed major tumor responses in early stage lung cancer patients and an increase in anti-tumor T-cells that remained after the tumor was removed.
Patients with early stage lung cancer administered nivolumab, an anti-PD-1 drug, prior to tumor removal surgery experienced increased anti-tumor immunity even after the tumor was removed, according to a study published in The New England Journal of Medicine.
Researchers at the Johns Hopkins Bloomberg Kimmel Institute for Cancer Immunotherapy and the Memorial Sloan-Kettering Cancer Center investigated patient tumors and immune systems prior to tumor removal surgery and then again after treatment for changes. After 21 patients received 2 doses of nivolumab before surgery, there was a major pathological response in 45% of the removed tumors and no delays in any of the planned surgeries.
According to the findings, neoantigen-specific T cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment, and some of these clones were not detected before the administration of nivolumab.
“Given that phase 3 clinical trials are underway, using this neoadjuvant anti-PD-1 drug will likely be practice changing,” Drew Pardoll, MD, PhD, senior author, said in a press release.
The researchers noted that the number of gene mutations in the tumor correlated closely with response to treatment and was a potential predictive marker for future studies.
“There was a major pathological response in almost half the patients, the tumor was almost totally overrun by lymphocytes at the time of resection, and we were able to demonstrate using a new assay we developed that tumor-specific T-cells spilled out into the blood after treatment,” Dr Pardoll said in the press release.
According to the researchers, neoadjuvant anti-PD-1 treatment could enhance the priming of anti-tumor T cells and potentially eliminate micro-metastatic cancer that can cause post-surgical relapse.
“That T-cells, activated by immunotherapy prior to surgery, can intercept rogue tumor cells throughout the body after the patient’s operation and prevent the cancer from recurring may be a game-changer,” Sung Poblete, PhD, RN, chief executive officer and president of Stand Up To Cancer, said in a press release.
Although the results are groundbreaking, larger studies are needed to define the role the anti-PD-1 in reducing recurrences and curing early stage cancers, the researchers concluded.
Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer.