Posted: Friday, December 23, 2022
The neoadjuvant use of atezolizumab seemed to be safe and active in patients with untreated, resectable stage IB–IIIB non–small cell lung cancer (NSCLC) prior to surgical resection, according to David P. Carbone, MD, PhD, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues. The results from the ongoing phase II Lung Cancer Mutation Consortium 3 (LCMC3) study, which were published in the journal Nature Medicine, also suggested the innate immune cell profiles in the pretreatment peripheral blood may predict pathologic response after neoadjuvant treatment with this monoclonal antibody.
A total of 181 patients received two doses of neoadjuvant atezolizumab monotherapy and were evaluable for safety. Of this population, 143 without EGFR or ALK alterations underwent tumor resection and were eligible for the primary efficacy analysis of major pathologic response (defined as ≤ 10% viable malignant cells).
A major pathologic response was reported in 20% of patients. In those who achieved an R0 margin status (n = 137), the 3-year overall survival rate was 80%. Fatigue (39%) and procedural pain (29%), along with expected immune-related toxicities, were the most frequently reported adverse events with atezolizumab monotherapy; this neoadjuvant treatment showed no unexpected safety findings.
An exploratory analysis revealed 14 immune cell subsets in the pretreatment peripheral blood that appeared to significantly correlate with major pathologic response. Immune cell subsets predictive of major pathologic response in the peripheral blood were also identified in the tumor microenvironment and were found to be associated with major pathologic response.
“We were surprised to find a correlation between high levels of natural killer cells and poor treatment outcomes,” commented Dr. Carbone in an Ohio State University Wexner Medical Center press release. “These new blood biomarkers offer us interesting new avenues for predicting treatment response and potential new targets for more effective immune-based drugs that target natural killer cells specifically.”
Disclosure: For full disclosures of the study authors, visit nature.com.