Safety and Efficacy Results From iSABR, a Phase 1 Study of Stereotactic ABlative Radiotherapy in Combination With Durvalumab for Early-Stage Medically Inoperable Non-Small Cell Lung Cancer

Abstract

To determine the safety and tolerability of combining stereotactic ablative radiotherapy (SABR) and durvalumab with respect to rates of Grade ≥3 non-hematological toxicity in medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). This was a prospective multicenter trial designed as a phase II study with phase I safety lead-in enrolling from 2017- 2020. Patients with biopsy-proven clinical stage I or IIA NSCLC (per AJCC 7th edition) and were medically inoperable or refused surgery, received 1 cycle of durvalumab followed by SABR or hypofractionated radiation (54 Gy in 3 fractions [fx], 50 Gy in 4 fx, or 65 Gy in 10 fx), then up to 4 additional cycles of durvalumab (1500 mg q4 weeks). Incidence of treatment-related Grade ≥3 toxicities were tabulated. Local control (LC), progression-free survival (PFS), overall survival (OS), and lung cancer specific mortality (LCSM) were assessed using the Kaplan-Meier method. 18 patients received combination SABR and durvalumab. With a median age of 79 years, 61.1% were male, 72.2% cT1, and 27.8% cT2. 88.9% of patients were treated to 54 Gy in 3 fx and 77.8% received all 5 cycles of durvalumab. The 1- and 2-year LC rates were 100% and 93.8%, 1- and 2-year PFS rates 94.4% and 83.3%, and 1- and 2-year OS rates 94.4% and 88.9%, respectively. The 2-year cumulative incidence for LCSM was 5.6%. Patients with acute and late Grade ≥3 treatment-related toxicities included pulmonary (27.8%, 5/18), cardiac (5.6%, 1/18), and GI (0%). One Grade 5 event in the setting of previously undiagnosed interstitial lung disease (ILD) was observed. For early-stage NSCLC, combination SABR and durvalumab resulted in excellent disease specific outcomes. Safety appeared acceptable per protocol, but 5/18 patients experienced Grade ≥3 pulmonary toxicity including one Grade 5 event in a patient with ILD. Results support ongoing phase III trials determining the benefit of SABR and immune check point inhibitors in this population.