Neoadjuvant Immunotherapy-Feasible and Promising for Patients with Early NSCLC
by Dr. C.H. Weaver M.D. 7/2019
The standard treatment of early stage non-small cell lung cancer (NSCLC) consists of surgical removal of the cancer followed by adjuvant chemotherapy to reduce the risk of cancer recurrence. (1) Small pilot studies have shown that neoadjuvant (preoperative) immune checkpoint inhibitor therapy may be of benefit in early-stage NSCLC, and the results of a recently published trial demonstrate neoadjuvant immune therapy is both feasible and effective. (2,3)
Checkpoint inhibitors are a precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells. A diagnostic test to measure the level of PD-L1 is available.
Results from studies evaluating anti-PD-1 and anti-PD-L1 checkpoint inhibitor therapies have demonstrated alone and in combination they are superior to chemotherapy and have become the standard of care in advanced NSCLC without driver mutations. (1-4)
Participants in the current clinical trial had surgically removable NSCLC ranging from stages IB to IIIB. Patients were treated with two cycles of the checkpoint inhibitor Tecentriq (atezolizumab), then had surgery to remove the lung cancer tissue.
The results in the first 101 participants in the trial were reported at the American Society of Clinical Oncology (ASCO) 2019 annual meeting. Of 90 evaluable Tecentriq treated patients 18% had a major pathologic response to the treatment, which was defined as 10% or fewer viable cancer cells detected in the surgically removed tumor tissue. Four patients had a pathological complete response, an absence of residual cancer following the neoadjuvant therapy. Seventy-two of the participants had stable disease, and four had their disease progress.
The standard of care in advanced NSCLC is treatment of all patients who have “non-driver” mutations with the combination of a checkpoint inhibitor and chemotherapy. (4) The currently study results suggest that neoadjuvant treatment with a checkpoint inhibitor medication is feasible. Ongoing trials will determine how best to incorporate checkpoint inhibitors into the overall management of early stage NSCLC.
The International Adjuvant Lung Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected Non-Small Cell Lung Cancer. New England Journal of Medicine. 2004;350:351-360.
N Engl J Med. 2018;378:1976
Gadgeel SM, Stevenson J, Langer C, et al. Pembrolizumab (pembro) plus chemotherapy as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C. J Clin Oncol 34, 2016 (suppl; abstr 9016).