Driver Variations Associated With Shorter PFS in Patients With NSCLC Receiving Chemoradiation and Durvalumab

A phase 3 cohort study identified driver variations associated with shorter progression-free survival (PFS) among patients with non-small cell lung cancer (NSCLC) receiving definitive chemoradiation and consolidative durvalumab.

“Consolidative durvalumab after definitive chemoradiation for unresectable locally advanced non–small cell lung cancer (NSCLC) can significantly improve [PFS] and overall survival (OS)," explained Yufei Liu, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues, adding “however, whether patients with driver variations derive equal benefit from this regimen remains unclear.”

The retrospective cohort study sought to compare outcomes of patients with locally advanced NSCLC with and without driver variations treated with definitive chemoradiation and consolidative durvalumab (PACIFIC regimen).

A total of 104 (53% [55] females and 88% [85] former or current smokers) patients with a median age of 65.1 years were examined from June 2017 through May 2020. Patients were treated with the PACIFIC regimen and stratified by KRAS-driver variation status. The primary outcomes of the study were PFS, OS, and second PFS.

Overall, 41% (n = 43) of patients had either KRAS or non-KRAS driver variations. Treatment with the PACIFIC regimen yielded a median PFS of 8.4 months for those with driver variations vs 40.1 months for those without driver variations (hazard ratio [HR] 2.75; 95% confidence interval [CI], 1.64 to 4.62; P <.001).). Median OS was not statistically different between patients with vs without driver variations (P = .24).

A total of 63 patients developed progressive disease, with a median PFS2 of 13.7 months and 4.4 months, respectively (HR, 0.37; 95% CI, 0.21 to 0.64; P = .001). Mutation status showed no effect on rates of treatment related toxic effects grade 2 or higher.

“These findings suggest the need to consider additional or alternative treatment options to the PACIFIC regimen for patients with driver variations,” concluded Dr Liu et al.

Source:                                        

Liu Y, Zhang Z, Rinsurongkawong W, et al. Association of Driver Oncogene Variations With Outcomes in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Consolidative Durvalumab. JAMA Netw Open. 2022;5(6):e2215589. doi:10.1001/jamanetworkopen.2022.15589