P2.12-20 NRG Oncology/Alliance LU005: A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab in LS-SCLC
Higgins K, Hu C, Ross H, Jabbour S, Kozono D, Owonikoko T, Movsas B, Xiao C, Solberg T, Williams T, Simko J, Wang X, Stinchcombe T, and Bradley J. P2.12-20 NRG Oncology/Alliance LU005: A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab in LS-SCLC. J Thorac Oncol 2019; 14(10):S821.
J Thorac Oncol
Background: Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation (ClinicalTrials.gov Identifier: NCT03811002). Method: Patients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab beginning concurrently with thoracic radiation, and continued every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), sex, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). It is hypothesized that the addition of atezolizumab will yield a hazard ratio of 0.62 for PFS, for a sample size of 280 patients in the phase II portion of this study. The overall sample size for phase II/III will be 506, with the OS analysis designed to provide at least 85% power to detect a hazard ratio of 0.71 at a 1-sided significance level of 0.025. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. This study includes a robust translational science component including blood and tissue based assays to further understand which patients may benefit most from immunotherapy. Result: This study activated in May 2019 and is currently enrolling patients. Conclusion: NRG Oncology/Alliance LU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. The estimated date of study completion is May 2024.