Durvalumab and consolidation SBRT following chemoradiation for stage III non-small cell lung cancer: A single institution pilot study.
Authors: Koffer Paul , Mistry Hetal , Hepel Jaroslaw T. , DiPetrillo Thomas A. , Wood Roxanne , Rosati Vallerie , Birnbaum Ariel E. , Azzoli Christopher G. , Khurshid Humera , Khan Hina 
Published: June 2024

e20085

Background: Definitive chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab (IO) demonstrated survival benefit and is now standard of care for Stage III Non-small Cell Lung Cancer (NSCLC). However, local-regional control (LRC) remains a concern with intrathoracic progression representing the most common site of failure. Adding stereotactic body radiotherapy (SBRT) boost may enhance the immunogenicity and antigenicity of tumor cells by regulating cell surface receptors and augmenting T-lymphocyte infiltration into tumor. SBRT boost also allows escalated dose to the primary tumor while minimizing dose to critical structures. Methods: Patients with Stage III NSCLC planned for definitive concurrent CRT with 1 year of consolidative IO were prospectively enrolled on a single institutional pilot trial. IO started 6-8 weeks after completion of CRT. SBRT was delivered between cycle 1 and 2 of IO to the residual, primary tumor (20 Gy in 2 fractions for peripheral, 19.5 Gy in 3 fractions for central tumors). Residual tumors needed to be < 120 cc. Lymph nodes were not boosted. Primary endpoints were grade (gr) ≥3 toxicities (CTCAE V4.03) and progression free survival (PFS). Secondary endpoints were Overall Survival (OS), LRC, and distant metastasis (DM). A sample size of 25 patients was proposed to determine safety and efficacy. Results: Accrual was slower than anticipated, and the study closed with 11 patients enrolled over 54 months. Slow accrual was due to a low rate of eligibility based on post CRT clinical status and SBRT target limitations. 1 patient withdrew consent before receiving treatment leaving 10 evaluable patients. Median age was 73 years and median CRT dose was 60 Gy (range 60-66 Gy). 6/10 of patient were adenocarcinoma. 5/10 pts had central tumor location. Median follow-up for evaluable patients is 2.2 years. OS was 90%, 70%, and 70% at 1-year, 2-years, and 3 years, respectively. PFS was 90%, 47%, and 47% at 1 year, 2 years, and 3 years, respectively. LRC was 100%, 83%, and 63% at 1 year, 2 years, and 3 years, respectively. Rates of DM were 0%, 12%, and 34% at 1 year, 2 years, and 3 years, respectively. 1 patient developed gr 3 pneumonitis requiring discontinuation of IO. 1 additional patient developed gr 2 pneumonitis requiring a brief pause in IO therapy and resumed IO without any further complications. One patient developed gr 5 myocarditis 29 days after the first dose of IO and 18 days after SBRT, on investigation deemed to be myocarditis secondary to IO. There was no other gr 3 toxicity attributable to IO or SBRT. Conclusions: The addition of SBRT to consolidative IO in stage III NSCLC patients treated with CRT was feasible. The single gr 5 toxicity was attributed to IO. SBRT boost demonstrated encouraging efficacy and manageable toxicity and merits further study. Our data adds to the growing evidence of harnessing tumor immunogenicity in enhancing IO responses. Clinical trial information: NCT03589547 .