Neoadjuvant Nivolumab Shows Promise Treating Lung Cancer

Nivolumab prior to tumor resection found safe in patients with early non-small cell lung cancer.

Findings from a recent study suggest that neoadjuvant immunotherapy before surgery may be beneficial to patients with early stage lung cancer.

Scientists in the study, which was presented at the European Society of Medical Oncology annual meeting, found that neoadjuvant immunotherapy with nivolumab is also feasible for these patients.

“Until now nivolumab and the other anti-PD-1 and anti-PD-L1 drug studies have only been reported in metastatic or advanced lung cancer,” said lead author Patrick Forde, MBBCh. “This was the first study of neoadjuvant PD-1 blockade in early stage lung cancer.”

In the study, scientists investigated whether treatment with nivolumab prior to resection would be safe and feasible in patients with early non-small cell lung cancers. The neoadjuvant treatment was considered feasible if it did not postpone resection, according to the study.

Included were 20 patients who underwent a biopsy. These patients received 2 doses of nivolumab 4 and 2 weeks prior to resection of the tumor. Scientists examined pretreatment biopsy tissue and examined the resected tumor post-treatment using PD-L1 staining, multiplex immunohistochemistry, and T cell receptor sequencing.

They also determined the level of pathological regression through a method that has been previously used in neoadjuvant chemotherapy in patients with non-small cell lung cancer (NSCLC). Tumors considered to have underwent major pathological regression had a resected tumor with less than 10% living cancer cells.

There were no significant effects on safety nor any delays to surgery, and approximately 40% of patients had a major pathological tumor regression, according to the study. These tumors either had a complete response to the treatment or isolated remaining cancer cells.

Other patients had some regression of their tumor, which is characterized by an infiltration of immune cells. The infiltration of immune cells was determined through multiplex immunohistochemistry, which can also identify new T cell clones that were not in the original biopsy.

“We found that neoadjuvant administration of nivolumab is safe and feasible in stage I-IIIA NSCLC and also a preliminary signal that anti-PD-1 immunotherapy may have activity in early stage lung cancer,” Dr Forde said. “Following these initial results we are expanding the study. One cohort will receive a third dose of nivolumab preoperatively and the other will receive the combination of nivolumab and ipilimumab preoperatively. This expanded study will continue to be conducted in collaboration with investigators at Johns Hopkins University and Memorial Sloan-Kettering Cancer Centre. Others, such as the Lung Cancer Mutation Consortium in the United States, are also conducting larger studies of neoadjuvant immune checkpoint inhibition in NSCLC.”