9 - Six-Year Overall Survival of Nivolumab Following Stereotactic Ablative Radiotherapy in Early-Stage Non-Small Cell Lung Cancer: Randomized I-SABR Trial
Presenter(s)
J. Y. Chang1, S. H. Lin1, W. Dong2, Z. Liao3, R. Maguire1, S. Gandhi3, C. M. Gay4, J. Zhang5, S. G. Chun2, Y. Elamin5, G. R. Blumenschein5, T. Cascone5, M. Altan5, R. Mehran6, A. B. Chen3, P. Balter7, J. Wu8, J. J. Lee9, P. Sharma2, and J. Heymach5; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6MD Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery, Houston, TX, 7Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 9MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Stereotactic ablative radiotherapy (SABR; BED >100 Gy in 1–10 fractions) yields high local control with low toxicity for early-stage non–small cell lung cancer (NSCLC), but regional and distant relapses remain common, especially for multiple primaries, or recurrent disease. To reduce recurrence and test the synergy of SABR plus immune checkpoint blockade, we conducted a randomized phase II trial comparing SABR alone versus SABR plus nivolumab (I-SABR) in node-negative (newly diagnosed or isolated parenchymal recurrence) NSCLC. The primary 4-year EFS and safety were reported in Lancet 2023; here we report 6-year overall survival (OS) and updated EFS.Materials/Methods:
From July 2017 to March 2022, patients with histologically confirmed =7 cm N0M0 treatment-naïve NSCLC or isolated parenchymal recurrent N0M0 NSCLC (after prior definitive surgery or radiotherapy/chemotherapy) were enrolled. Key exclusions included prior immune checkpoint inhibitors or contraindications to SABR or immunotherapy. Patients were randomized to SABR alone or SABR plus monthly nivolumab 480 mg for four doses (first dose before or within 36 hours after the first SABR fraction). Follow-up included chest CT or PET/CT and clinical visits every 3 months for 2 years, then every 6 months for 3 years, then annually. EFS was defined as time from randomization to recurrence (local, regional, distant, or second primary lung cancer) or death (clinicaltrials.gov NCT03110978).Results:
Median follow-up was 68.6 months (95% CI 62.0–72.7). Among 141 patients, 48 (34%) died and 93 (66%) were alive at last follow-up. Survival distributions differed by arm (log-rank p = 0.0466). I-SABR improved OS (HR 0.548; 95% CI 0.301–1.000; p = 0.05, Cox model) and EFS (HR 0.516; 95% CI 0.323–0.825; p = 0.0057). Six-year OS and EFS were higher with I-SABR versus SABR (OS: 70% vs. 56%, p = 0.0466; EFS: 53% vs. 32%, p = 0.0049). Subgroup analyses suggested consistent benefit across key clinical strata, though some comparisons were underpowered. Toxicities were generally manageable and consistent with prior reports, with low rates of grade 3 events attributable to nivolumab. Patterns of failure and salvage treatments are analyzed. Immunologic correlative analyses are ongoing to elucidate mechanisms and biomarkers; clinical and radiomic AI-guided individualized immunotherapy strategies are being developed.
Conclusion:
Adding four doses of nivolumab to SABR significantly improved 6-year OS and EFS versus SABR alone in treatment-naïve or isolated-parenchymal-recurrence, node-negative NSCLC, with tolerable toxicity. I-SABR warrants consideration as a novel approach for this population. Optimization of timing, sequencing, and duration of I-SABR is crucial for future research, and individual selection of immunotherapy may further improve clinical efficacy.