Advances in Oncology

While neoadjuvant chemotherapy is an accepted treatment approach for resectable non-small cell lung cancer, the cancer recurs in 30 to 70 percent of patients, who then often ultimately succumb to the disease. A multicenter phase 2 clinical trial designed and spearheaded by oncology faculty at the Herbert Irving Comprehensive Cancer Center at Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian/Columbia University Irving Medical Center evaluated a combination of chemotherapy and immunotherapy in the preoperative setting – a novel approach that appears to be working.

The researchers tested the activity of the PD-L1 inhibitor, atezolizumab, with carboplatin and nab-paclitaxel given as neoadjuvant treatment before surgical resection. Previously atezolizumab had been studied only in the metastatic setting for lung cancer. Their findings, published in the June 1, 2020, issue of The Lancet Oncology, suggest that this combination therapy could be promising for patients with resectable non-small cell lung cancer.

To the researchers’ knowledge, this study is the first published trial of chemotherapy combined with a PD-L1 inhibitor in the neoadjuvant treatment setting for non-small cell lung cancer. More than 75 percent of the 30 patients enrolled presented with stage IIIA disease. Even in this high-risk population of patients, 33 percent had a pathological complete response and 57 percent had a major pathological response as indicated by the presence of 10 percent or less residual viable tumor at the time of surgery. At a median follow-up of 12.9 months from the first day of treatment, 19 patients were alive and had no evidence of disease. There were no treatment-related surgical delays, and treatment-related toxic effects were manageable.

If pathological response can be validated as a predictive biomarker for survival, the researchers expect that the novel regimen could be a landscape-changing therapy, also hopefully paving the way towards a shorter time interval between clinical trials and FDA approval.