221MO Stereotactic body radiotherapy (SBRT) followed by durvalumab in early-stage non-small cell lung cancer (NSCLC) patients: Results from a randomized phase II trial (ASTEROID)

Background: SBRT is the standard treatment for early-stage NSCLC patients, unfit for surgery, and SBRT is associated with excellent results in terms of local control.However, an important proportion of patients develop distant metastases over time.Adjuvant chemotherapy is rarely administered due to lack of data and the frailty of this population.Theoretically, immunotherapy is an attractive option, often being well tolerated and with a potential synergistic effect in combination with radiation.The ASTEROID trial aimed to assess whether the addition of durvalumab improves tumour control after SBRT in peripheral T 1-2 N0M0 tumours. Methods:Randomized multicentre open-label phase II study comparing SBRT alone in 3-4 fractions (arm A) with SBRT followed by durvalumab 1500 mg i.v.every 4 weeks for 12 months (arm B).Primary endpoint was time to progression (TTP), with disease free survival (DFS) and overall survival (OS) as secondary endpoints.The significance level was defined as a one-sided of 0.10.Results: 104 patients were included between 2018 and 2024 at 12 Nordic hospitals.57% were women, 71% had adenocarcinomas, 83% had T1A tumours, 33% had PS 0, 67% PS 1-2.The median age was 78 (56-89) years and the mean FEV1 was 1.8 (range 0.7-4.5)L. The median number of durvalumab infusions were 11 (1-12).Adverse events (CTCAE v4.0) related to SBRT were reported in 22 of 54 patients (41%) in arm A and 15 of 49 (31%) in arm B, where the most common events were grade 1-2 fatigue, cough, pain and dyspnea, with one grade 3 pneumonitis in arm A. In arm B 36 of 49 patients (73%) reported AEs related to durvalumab, mainly grade 1 and 2, where the most common events were skin reactions (39%), pruritus (24%) and fatigue (22%) and two patients experienced symptomatic grade 3 events (skin reaction and pneumonitis).At data cut off with a median follow-up time of 33 months (13-64), ten patients in arm A and three patients in arm B had progressed with a significantly improved TTP (p=0,054) with the addition of durvalumab, but no difference in DFS or OS.Conclusions: Adding durvalumab after SBRT appears to reduce tumour progression, but the clinical value in this frail population with high competing mortality remains uncertain.