SWOG/NRG S1914: A Randomized Phase III Trial of Induction/Consolidation Atezolizumab + SBRT vs. SBRT Alone in High Risk, Early-Stage NSCLC (NCT#04214262)

Abstract

<h3>Purpose/Objective(s)</h3> Stereotactic radiotherapy (SBRT) is the standard of care for early stage, medically inoperable non-small cell lung cancer (NSCLC). While rates of in-field control exceed 90% in prospective trials, rates of regional and distant control after SBRT remain suboptimal, and adjuvant chemotherapy is rarely used in this typically frail patient population. SWOG/NRG S1914 is a randomized phase III trial testing the addition of neoadjuvant, concurrent, and adjuvant atezolizumab to SBRT for early-stage NSCLC. <h3>Materials/Methods</h3> Eligible patients have T1-3N0M0 NSCLC ≤7cm and are medically inoperable or declined surgery. Patients must have at least one risk factor suggestive of increased risk of recurrence: tumor diameter ≥2 cm, SUV_max ≥6.2, or moderately/poorly/undifferentiated differentiated histology. Patients are randomized 1:1 to standard-of-care SBRT or to neoadjuvant, concurrent, and adjuvant atezolizumab 1200 mg IV Q3 week with SBRT initiated with cycle 3. Standard SBRT schedules of 3-5 fractions with a BED ≥100 are permitted. Stratification factors include location (central versus peripheral), size (<4 cm versus ≥4cm), and Zubrod performance status (0-1 vs 2). The primary objective of the study is to compare overall survival between the arms. The accrual goal is 480 patients to achieve 432 eligible patients based on a design with 80% power to rule out a null hazard ratio at the 1-sided 0.025 level, if the true hazard ratio were 0.70. The estimated duration of accrual and follow-up are 60 and 36 months, respectively and includes 4 interim analyses evaluating early stopping for futility or efficacy. Secondary objectives include comparisons of progression free survival (PFS), distant, locoregional and local failure rates, toxicity, and quality of life (EORTC QLQ-C30 and EORTC QLQ-LC13). <h3>Results</h3> Enrollment began 08/13/2020. As of 02/23/2022, 284 sites have been approved to enroll patients. 80 patients have enrolled and undergone randomization. <h3>Conclusion</h3> SWOG/NRG S1914 is a randomized phase III trial testing the addition of neoadjuvant, concurrent, and adjuvant atezolizumab to SABR in early-stage NSCLC.