Durvalumab in frail and older patients with stage iv non-small cell lung cancer: The randomized phase ii duration trial

ABSTRACT

Introduction: Checkpoint inhibitors have recently been established as first-line treatment for metastatic NSCLC. Notably, a phenomenon known as immunosenescence, i.e. the progressive remodeling of the immune system with aging, as well as the inflammatory status, may interfere with the activity of PD-1/PD-L1 inhibitors. Although frail and older patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, this population is still underrepresented in most clinical trials. Thus, clinical evidence about tolerability and efficacy of these novel agents in the elder and frail population is urgently required. Methods/Design: DURATION (NCT03345810) is a prospective, open label, treatment stratified, randomized, multicenter phase II study. The protocol foresaw the enrollment of 200 patients diagnosed with stage IV NSCLC ≥70 years old and/or with Charlson-Comorbidity Index > 1 and/ or with a performance status ECOG > 1. Patients were stratified according to Cancer and Age Research Group (CARG) score in 'fit' and 'less fit'. Patients were then randomized 11 to receive either CT or two cycles of CT followed by two cycles of durvalumab and durvalumab maintenance. Details are shown in figure 1. The primary endpoint is the rate of treatment-related grade III/IV adverse events. Secondary endpoints are progression-free survival, response rate and overall survival and quality of life assessment. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Results: The last patient was enrolled in January 2021. Forty-nine, 48, 51, and 52 patients were allocated to arm A, arm B, arm C, and arm D, respectively. Currently, 145 patients have completed the study, 13 patients are under treatment (12 in total in durvalumab-maintenance arms and 1 in the CT arm), while 42 are in follow-up. Conclusions: Inspite of the COVID-19 pandemic, the DURATION trial successfully completed the planned enrollment of 200 patients, underlying the urgent need for evidence of efficacy and tolerability of immunotherapy in the challenging population of frail and elderly patients.