Chicago, Illinois—Interim data from a large study of patients with early-stage non–small-cell lung cancer (NSCLC) being presented at the 2019 ASCO Annual Meeting show that neoadjuvant atezolizumab is well-tolerated, and yields encouraging responses.

“Small pilot studies…have shown that preoperative immune checkpoint inhibitor therapy may be of benefit in early-stage NSCLC. This large multicenter trial assesses the benefit of neoadjuvant treatment with atezolizumab,” explained David J. Kwiatkowski, MD, PhD, Senior Physician, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

Patients with stages IB to IIIB, resectable NSCLC were enrolled in the study and given 2 cycles of atezolizumab 1200 mg before undergoing resection. Before administering atezolizumab as well as at surgery, Dr Kwiatkowski et al obtain primary tumor +/- node biopsies and blood samples for biomarker studies.

The primary end point of the study is major pathological response (MPR; ie, ≤10% viable tumor cells in the resection specimen), and secondary end points include safety and correlation of response with PD-L1 expression, tumor mutation burden (TMB), and gene expression signatures.

Dr Kwiatkowski and his team evaluated interim efficacy data by analyzing the first 101 of 180 planned patients (median age, 64 years; 23 current and 68 former smokers; 66 with nonsquamous NSCLC); 11, 16, 28, 39, and 7 of whom had clinical stages IB, IIA, IIB, IIIA, and IIIB, respectively.

There were 2 grade 5 treatment-unrelated adverse events reported (ie, cardiac death postsurgical resection and death due to disease progression) and 29 grade 3-4 adverse events, 6% of which were treatment-related.

Overall, 90 patients underwent surgery. A total of 8 patients had driver mutations (7, EGFR; 1, ALK) and no MPR; of the remaining 82 patients, the MPR rate was 15 (18%; 95% CI, 11%-28%), and 4 patients had pathological complete response (pCR).

Of 101 patients included in the interim analysis, exome sequencing data were available for 47. The median TMB was 10.4 mutations per Mb, and did not differ in patients with and without MPR.

Dr Kwiatkowski et al are still analyzing TMB, mutation signatures, and gene expression profiling.

“Atezo[lizumab] in the neoadjuvant setting was well tolerated, and pCR and MPR rates are encouraging in this large multicenter trial. Efficacy interim analysis passed its futility boundary, and study enrollment continues,” they concluded.—Hina Khaliq

Kwiatkowski DJ, Rusch VW, Chaft JE, et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3). Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8503.