New data show that the immuno-oncology drug atezolizumab may be a safe and effective treatment for patients with stage IB to IIIB non–small cell lung cancer (NSCLC) prior to surgery, according to a study led by researchers with The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC–James) as part of the national Lung Cancer Mutation Consortium 3 study. Their findings were published by Chaft et al in Nature Medicine.
Researchers found that the survival of patients in this new study was far better—about 80% at 3 years posttreatment and approximately twice as good as what could be expected with surgery and chemotherapy alone. Investigators also reported data showing that the presence of high numbers of natural killer (NK) cells was associated with poor immunotherapy treatment effectiveness in this study. Patients with high levels of these cells might benefit from the addition of NK-specific therapy.
David Carbone, MD, PhD
Led by David Carbone, MD, PhD, corresponding author and principal investigator of the trial, and Director of the James Thoracic Center at the OSUCCC–James, this national clinical trial involved 181 patients recruited from 15 cancer centers across the United States. It represents the largest clinical study evaluating the use of any immuno-oncology drug given without chemotherapy prior to surgery for patients with stage IB to IIIB NSCLC.
The U.S. Food and Drug Administration (FDA) recently approved the combination of chemotherapy and immunotherapy given prior to surgery for the treatment of NSCLC, but this study showed that some patients may not need the added toxicity of chemotherapy. However, giving immuno-oncology treatments alone prior to lung cancer surgery is still considered experimental.
“Immuno-oncology drugs have truly transformed treatment outcomes for metastatic lung cancer, but its impact and optimal use in earlier-stage cancers is still being determined," Dr. Carbone said.
Dr. Carbone noted that one large study evaluating the combination of immunotherapy and chemotherapy before surgery has been reported, and several others are ongoing. These studies suggest that this pairing is effective at reducing relapses after surgery, however, Dr. Carbone pointed out that the impact of chemotherapy and immunotherapy on overall survival has not yet been demonstrated.
Study Methods and Results
In the current study, researchers sought to gather a more definitive picture of direct immuno-oncology treatment benefits by collecting pre- and postsurgery pathologic samples and peripheral blood to measure immune cell profiles that correlated with clinical benefits.
“We were surprised to find a correlation between high levels of NK cells and poor treatment outcomes. 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 NK cells specifically,” Dr. Carbone said.
The researchers found that 20% of patients with NSCLC treated with two cycles of neoadjuvant atezolizumab experienced a major pathologic response before time of surgery. Major pathologic response was defined in this study as having less than 10% of viable cancer cells existing in the tumor at the time of surgery, indicating most cancer cells in the tumor tissue had been destroyed by the neoadjuvant immunotherapy course. Additionally, about 7% of patients had a complete pathologic response when treated with just these two doses of neoadjuvant immunotherapy.
“These are very encouraging results with significant clinical care implications. But what is even more striking is that we were able to identify and correlate specific findings in the blood before treatment that predicted treatment outcomes, and identified potential new therapy targets,” said Dr. Carbone.
Disclosure: The study received sponsorship support from Genentech for clinical study costs and immune cell analysis at OSUCCC–James. Dr. Carbone is a consultant for Genentech, manufacturer of the immuno-oncology drug atezolizumab used in this study. For full disclosures of the study authors, visit nature.com.
